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Volume 8
Issue 2
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Viruses, Volume 8, Issue 2 (February 2016) – 29 articles

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4001 KiB  
Article
Porcine Circovirus 2 Deploys PERK Pathway and GRP78 for Its Enhanced Replication in PK-15 Cells
by Yingshan Zhou, Baozhu Qi, Yuanxing Gu, Fei Xu, Huahua Du, Xiaoliang Li and Weihuan Fang
Viruses 2016, 8(2), 56; https://doi.org/10.3390/v8020056 - 20 Feb 2016
Cited by 45 | Viewed by 8655
Abstract
Porcine circovirus type 2 (PCV2) infection induces autophagy and apoptosis. These cellular responses could be connected with endoplasmic reticulum (ER) stress. It remains unknown if PCV2 induces ER stress and if autophagy or apoptosis is primary to PCV2 infection or secondary responses following [...] Read more.
Porcine circovirus type 2 (PCV2) infection induces autophagy and apoptosis. These cellular responses could be connected with endoplasmic reticulum (ER) stress. It remains unknown if PCV2 induces ER stress and if autophagy or apoptosis is primary to PCV2 infection or secondary responses following ER stress. Here, we demonstrate that PCV2 triggered unfolded protein response (UPR) in PK-15 cells by activating the PERK/eIF2α pathway without concomitant activation of IRE1 or ATF6. Since ATF4 and CHOP were induced later than PERK/eIF2α, it is clear that persistent PCV2 infection could lead to selective activation of PERK via the PERK-eIF2α-ATF4-CHOP axis. Therefore, PERK activation could be part of the pro-apoptotic signaling via induced expression of CHOP by PCV2. Since PERK inhibition by GSK2606414 or RNA silencing or suppression of eIF2α dephosphorylation by salubrinal limited viral replication, we suppose that PCV2 deploys UPR to enhance its replication. Over-expression of GRP78 or treatment with tauroursodeoxycholic acid could enhance viral capsid expression and/or viral titers, indicating that these chaperones, endogenous or exogenous, could help correct folding of viral proteins. Our findings provide the first evidence that ER stress plays a role in the pathogenesis of PCV2 infection probably as part of autophagic and apoptotic responses. Full article
(This article belongs to the Section Animal Viruses)
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Article
A Toolbox for Herpesvirus miRNA Research: Construction of a Complete Set of KSHV miRNA Deletion Mutants
by Vaibhav Jain, Karlie Plaisance-Bonstaff, Rajnikumar Sangani, Curtis Lanier, Alexander Dolce, Jianhong Hu, Kevin Brulois, Irina Haecker, Peter Turner, Rolf Renne and Brian Krueger
Viruses 2016, 8(2), 54; https://doi.org/10.3390/v8020054 - 19 Feb 2016
Cited by 30 | Viewed by 6865
Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes 12 viral microRNAs (miRNAs) that are expressed during latency. Research into KSHV miRNA function has suffered from a lack of genetic systems to study viral miRNA mutations in the context of the viral genome. We used the Escherichia [...] Read more.
Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes 12 viral microRNAs (miRNAs) that are expressed during latency. Research into KSHV miRNA function has suffered from a lack of genetic systems to study viral miRNA mutations in the context of the viral genome. We used the Escherichia coli Red recombination system together with a new bacmid background, BAC16, to create mutants for all known KSHV miRNAs. The specific miRNA deletions or mutations and the integrity of the bacmids have been strictly quality controlled using PCR, restriction digestion, and sequencing. In addition, stable viral producer cell lines based on iSLK cells have been created for wildtype KSHV, for 12 individual miRNA knock-out mutants (ΔmiR-K12-1 through -12), and for mutants deleted for 10 of 12 (ΔmiR-cluster) or all 12 miRNAs (ΔmiR-all). NGS, in combination with SureSelect technology, was employed to sequence the entire latent genome within all producer cell lines. qPCR assays were used to verify the expression of the remaining viral miRNAs in a subset of mutants. Induction of the lytic cycle leads to efficient production of progeny viruses that have been used to infect endothelial cells. Wt BAC16 and miR mutant iSLK producer cell lines are now available to the research community. Full article
(This article belongs to the Section Animal Viruses)
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Article
Identification of Known and Novel Recurrent Viral Sequences in Data from Multiple Patients and Multiple Cancers
by Jens Friis-Nielsen, Kristín Rós Kjartansdóttir, Sarah Mollerup, Maria Asplund, Tobias Mourier, Randi Holm Jensen, Thomas Arn Hansen, Alba Rey-Iglesia, Stine Raith Richter, Ida Broman Nielsen, David E. Alquezar-Planas, Pernille V. S. Olsen, Lasse Vinner, Helena Fridholm, Lars Peter Nielsen, Eske Willerslev, Thomas Sicheritz-Pontén, Ole Lund, Anders Johannes Hansen, Jose M. G. Izarzugaza and Søren Brunakadd Show full author list remove Hide full author list
Viruses 2016, 8(2), 53; https://doi.org/10.3390/v8020053 - 19 Feb 2016
Cited by 10 | Viewed by 8203
Abstract
Virus discovery from high throughput sequencing data often follows a bottom-up approach where taxonomic annotation takes place prior to association to disease. Albeit effective in some cases, the approach fails to detect novel pathogens and remote variants not present in reference databases. We [...] Read more.
Virus discovery from high throughput sequencing data often follows a bottom-up approach where taxonomic annotation takes place prior to association to disease. Albeit effective in some cases, the approach fails to detect novel pathogens and remote variants not present in reference databases. We have developed a species independent pipeline that utilises sequence clustering for the identification of nucleotide sequences that co-occur across multiple sequencing data instances. We applied the workflow to 686 sequencing libraries from 252 cancer samples of different cancer and tissue types, 32 non-template controls, and 24 test samples. Recurrent sequences were statistically associated to biological, methodological or technical features with the aim to identify novel pathogens or plausible contaminants that may associate to a particular kit or method. We provide examples of identified inhabitants of the healthy tissue flora as well as experimental contaminants. Unmapped sequences that co-occur with high statistical significance potentially represent the unknown sequence space where novel pathogens can be identified. Full article
(This article belongs to the Special Issue Next Generation Sequencing: New Developments and Discoveries in Virology)
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Article
In Vitro and in Vivo Evaluation of Mutations in the NS Region of Lineage 2 West Nile Virus Associated with Neuroinvasiveness in a Mammalian Model
by Katalin Szentpáli-Gavallér, Stephanie M. Lim, László Dencső, Krisztián Bányai, Penelope Koraka, Albert D.M.E. Osterhaus, Byron E.E. Martina, Tamás Bakonyi and Ádám Bálint
Viruses 2016, 8(2), 49; https://doi.org/10.3390/v8020049 - 19 Feb 2016
Cited by 12 | Viewed by 6620
Abstract
West Nile virus (WNV) strains may differ significantly in neuroinvasiveness in vertebrate hosts. In contrast to genetic lineage 1 WNVs, molecular determinants of pathogenic lineage 2 strains have not been experimentally confirmed so far. A full-length infectious clone of a neurovirulent WNV lineage [...] Read more.
West Nile virus (WNV) strains may differ significantly in neuroinvasiveness in vertebrate hosts. In contrast to genetic lineage 1 WNVs, molecular determinants of pathogenic lineage 2 strains have not been experimentally confirmed so far. A full-length infectious clone of a neurovirulent WNV lineage 2 strain (578/10; Central Europe) was generated and amino acid substitutions that have been shown to attenuate lineage 1 WNVs were introduced into the nonstructural proteins (NS1 (P250L), NS2A (A30P), NS3 (P249H) NS4B (P38G, C102S, E249G)). The mouse neuroinvasive phenotype of each mutant virus was examined following intraperitoneal inoculation of C57BL/6 mice. Only the NS1-P250L mutation was associated with a significant attenuation of virulence in mice compared to the wild-type. Multiplication kinetics in cell culture revealed significantly lower infectious virus titres for the NS1 mutant compared to the wild-type, as well as significantly lower amounts of positive and negative stranded RNA. Full article
(This article belongs to the Section Animal Viruses)
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Article
Infectious Salmon Anaemia Virus (ISAV) RNA Binding Protein Encoded by Segment 8 ORF2 and Its Interaction with ISAV and Intracellular Proteins
by Christel M. Olsen, Turhan Markussen, Bernd Thiede and Espen Rimstad
Viruses 2016, 8(2), 52; https://doi.org/10.3390/v8020052 - 18 Feb 2016
Cited by 8 | Viewed by 5940
Abstract
Infectious salmon anaemia virus (ISAV) is an orthomyxovirus infecting salmonid fish. The virus is adapted to low temperature and has a replication optimum between 10–15 °C. In this study the subcellular localization and protein interactions for the protein encoded by the largest open [...] Read more.
Infectious salmon anaemia virus (ISAV) is an orthomyxovirus infecting salmonid fish. The virus is adapted to low temperature and has a replication optimum between 10–15 °C. In this study the subcellular localization and protein interactions for the protein encoded by the largest open reading frame of gene segment 8 (s8ORF2) were investigated. In ISAV infected cells the s8ORF2 protein was found mainly in the cytosol but a minor fraction of cells expressed the protein in the nucleus as well. Green fluorescent protein-tagged s8ORF2 did not leak out of the cell when the plasma membrane was permeabilized, suggesting interactions with intracellular structural components. The s8ORF2 protein exists both as monomer and homodimer, and co-immunoprecipitation experiments strongly suggests it binds to the ISAV fusion-, nucleo- and matrix proteins. Two versions of s8ORF2 were detected with apparent molecular weights of 24–26 and 35 kDa in lysates of infected cells. The 35 kDa type is an early viral protein while the smaller version appears during the later phases of infection. The 24–26 kDa type was also the predominant form in viral particles. The s8ORF2 protein has previously been shown to bind RNA and interfere with interferon induction and signaling. Here we found that a fraction of the s8ORF2 protein pool in infected cells is likely to be conjugated to the interferon stimulated gene 15 (ISG15) and ubiquitin. Furthermore, several endogenous proteins pulled down by the s8ORF2 protein were identified by liquid chromatography mass spectrometry (LC-MS). Full article
(This article belongs to the Section Animal Viruses)
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Article
The Pathogenesis of Saffold Virus in AG129 Mice and the Effects of Its Truncated L Protein in the Central Nervous System
by Shawn Zheng Kai Tan, Kaw Bing Chua, Yishi Xu and Mookkan Prabakaran
Viruses 2016, 8(2), 24; https://doi.org/10.3390/v8020024 - 18 Feb 2016
Cited by 5 | Viewed by 5253
Abstract
Saffold Virus (SAFV) is a human cardiovirus that has been suggested to cause severe infection of the central nervous system (CNS). Compared to a similar virus, Theiler’s murine encephalomyelitis virus (TMEV), SAFV has a truncated Leader (L) protein, a protein essential in the [...] Read more.
Saffold Virus (SAFV) is a human cardiovirus that has been suggested to cause severe infection of the central nervous system (CNS). Compared to a similar virus, Theiler’s murine encephalomyelitis virus (TMEV), SAFV has a truncated Leader (L) protein, a protein essential in the establishment of persistent CNS infections. In this study, we generated a chimeric SAFV by replacing the L protein of SAFV with that of TMEV. We then compared the replication in cell cultures and pathogenesis in a mouse model. We showed that both SAFV and chimeric SAFV are able to infect Vero and Neuro2a cells well, but only chimeric SAFV was able to infect RAW264.7. We then showed that mice lacking IFN-α/β and IFN-γ receptors provide a good animal model for SAFV infection, and further identified the locality of the infection to the ventral horn of the spine and several locations in the brain. Lastly, we showed that neither SAFV nor chimeric SAFV causes persistence in this model. Overall, our results provide a strong basis on which the mechanisms underlying Saffold virus induced neuropathogenesis can be further studied and, hence, facilitating new information about its pathogenesis. Full article
(This article belongs to the Section Animal Viruses)
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Article
NF45 and NF90 Bind HIV-1 RNA and Modulate HIV Gene Expression
by Yan Li and Michael Belshan
Viruses 2016, 8(2), 47; https://doi.org/10.3390/v8020047 - 16 Feb 2016
Cited by 15 | Viewed by 6252
Abstract
A previous proteomic screen in our laboratory identified nuclear factor 45 (NF45) and nuclear factor 90 (NF90) as potential cellular factors involved in human immunodeficiency virus type 1 (HIV-1) replication. Both are RNA binding proteins that regulate gene expression; and NF90 has been [...] Read more.
A previous proteomic screen in our laboratory identified nuclear factor 45 (NF45) and nuclear factor 90 (NF90) as potential cellular factors involved in human immunodeficiency virus type 1 (HIV-1) replication. Both are RNA binding proteins that regulate gene expression; and NF90 has been shown to regulate the expression of cyclin T1 which is required for Tat-dependent trans-activation of viral gene expression. In this study the roles of NF45 and NF90 in HIV replication were investigated through overexpression studies. Ectopic expression of either factor potentiated HIV infection, gene expression, and virus production. Deletion of the RNA binding domains of NF45 and NF90 diminished the enhancement of HIV infection and gene expression. Both proteins were found to interact with the HIV RNA. RNA decay assays demonstrated that NF90, but not NF45, increased the half-life of the HIV RNA. Overall, these studies indicate that both NF45 and NF90 potentiate HIV infection through their RNA binding domains. Full article
(This article belongs to the Section Animal Viruses)
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Article
Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein
by Kristina Kakalacheva, Stephan Regenass, Silke Wiesmayr, Tarik Azzi, Christoph Berger, Russell C. Dale, Fabienne Brilot, Christian Münz, Kevin Rostasy, David Nadal and Jan D. Lünemann
Viruses 2016, 8(2), 51; https://doi.org/10.3390/v8020051 - 12 Feb 2016
Cited by 22 | Viewed by 6962
Abstract
A history of infectious mononucleosis (IM), symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses. Antibody [...] Read more.
A history of infectious mononucleosis (IM), symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses. Antibody responses towards cellular antigens using a HEp-2 based indirect immunofluorescence assay and native myelin oligodendrocyte glycoprotein (MOG) using a flow cytometry-based assay were determined in 35 patients with IM and in 23 control subjects. We detected frequent immunoglobulin M (IgM) reactivity to vimentin, a major constituent of the intermediate filament family of proteins, in IM patients (27/35; 77%) but rarely in control subjects (2/23; 9%). IgG autoantibodies binding to HEp-2 cells were absent in both groups. In contrast, IgG responses to native MOG, present in up to 40% of children with inflammatory demyelinating diseases of the central nervous system (CNS), were detectable in 7/35 (20%) patients with IM but not in control subjects. Normalization of anti-vimentin IgM levels to increased total IgM concentrations during IM resulted in loss of significant differences for anti-vimentin IgM titers. Anti-MOG specific IgG responses were still detectable in a subset of three out of 35 patients with IM (9%), even after normalization to increased total IgG levels. Vimentin-specific IgM and MOG-specific IgG responses decreased following clinical resolution of acute IM symptoms. We conclude from our data that MOG-specific memory B cells are activated in subset of patients with IM. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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Review
Structural Proteomics of Herpesviruses
by Baptiste Leroy, Laurent Gillet, Alain Vanderplasschen and Ruddy Wattiez
Viruses 2016, 8(2), 50; https://doi.org/10.3390/v8020050 - 12 Feb 2016
Cited by 18 | Viewed by 6873
Abstract
Herpesviruses are highly prevalent viruses associated with numerous pathologies both in animal and human populations. Until now, most of the strategies used to prevent or to cure these infections have been unsuccessful because these viruses have developed numerous immune evasion mechanisms. Therefore, a [...] Read more.
Herpesviruses are highly prevalent viruses associated with numerous pathologies both in animal and human populations. Until now, most of the strategies used to prevent or to cure these infections have been unsuccessful because these viruses have developed numerous immune evasion mechanisms. Therefore, a better understanding of their complex lifecycle is needed. In particular, while the genome of numerous herpesviruses has been sequenced, the exact composition of virions remains unknown for most of them. Mass spectrometry has recently emerged as a central method and has permitted fundamental discoveries in virology. Here, we review mass spectrometry-based approaches that have recently allowed a better understanding of the composition of the herpesvirus virion. In particular, we describe strategies commonly used for proper sample preparation and fractionation to allow protein localization inside the particle but also to avoid contamination by nonstructural proteins. A collection of other important data regarding post-translational modifications or the relative abundance of structural proteins is also described. This review also discusses the poorly studied importance of host proteins in herpesvirus structural proteins and the necessity to develop a quantitative workflow to better understand the dynamics of the structural proteome. In the future, we hope that this collaborative effort will assist in the development of new strategies to fight these infections. Full article
(This article belongs to the Section Animal Viruses)
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Article
Genetic Variability of HIV-1 for Drug Resistance Assay Development
by Dana S. Clutter, Patricia Rojas Sánchez, Soo-Yon Rhee and Robert W. Shafer
Viruses 2016, 8(2), 48; https://doi.org/10.3390/v8020048 - 11 Feb 2016
Cited by 14 | Viewed by 5046
Abstract
A hybridization-based point-of-care (POC) assay for HIV-1 drug resistance would be useful in low- and middle-income countries (LMICs) where resistance testing is not routinely available. The major obstacle in developing such an assay is the extreme genetic variability of HIV-1. We analyzed 27,203 [...] Read more.
A hybridization-based point-of-care (POC) assay for HIV-1 drug resistance would be useful in low- and middle-income countries (LMICs) where resistance testing is not routinely available. The major obstacle in developing such an assay is the extreme genetic variability of HIV-1. We analyzed 27,203 reverse transcriptase (RT) sequences from the Stanford HIV Drug Resistance Database originating from six LMIC regions. We characterized the variability in a 27-nucleotide window surrounding six clinically important drug resistance mutations (DRMs) at positions 65, 103, 106, 181, 184, and 190. The number of distinct codons at each DRM position ranged from four at position 184 to 11 at position 190. Depending on the mutation, between 11 and 15 of the 24 flanking nucleotide positions were variable. Nonetheless, most flanking sequences differed from a core set of 10 flanking sequences by just one or two nucleotides. Flanking sequence variability was also lower in each LMIC region compared with overall variability in all regions. We also describe an online program that we developed to perform similar analyses for mutations at any position in RT, protease, or integrase. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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Article
Suppressive Effects of the Site 1 Protease (S1P) Inhibitor, PF-429242, on Dengue Virus Propagation
by Leo Uchida, Shuzo Urata, Gianne Eduard L. Ulanday, Yuki Takamatsu, Jiro Yasuda, Kouichi Morita and Daisuke Hayasaka
Viruses 2016, 8(2), 46; https://doi.org/10.3390/v8020046 - 10 Feb 2016
Cited by 30 | Viewed by 6986
Abstract
Dengue virus (DENV) infection causes one of the most widespread mosquito-borne diseases in the world. Despite the great need, effective vaccines and practical antiviral therapies are still under development. Intracellular lipid levels are regulated by sterol regulatory elements-binding proteins (SREBPs), which are activated [...] Read more.
Dengue virus (DENV) infection causes one of the most widespread mosquito-borne diseases in the world. Despite the great need, effective vaccines and practical antiviral therapies are still under development. Intracellular lipid levels are regulated by sterol regulatory elements-binding proteins (SREBPs), which are activated by serine protease, site 1 protease (S1P). Small compound PF-429242 is known as a S1P inhibitor and the antivirus effects have been reported in some viruses. In this study, we examined the anti-DENV effects of PF-429242 using all four serotypes of DENV by several primate-derived cell lines. Moreover, emergence of drug-resistant DENV mutants was assessed by sequential passages with the drug. DENV dependency on intracellular lipids during their infection was also evaluated by adding extracellular lipids. The addition of PF-429242 showed suppression of viral propagation in all DENV serotypes. We showed that drug-resistant DENV mutants are unlikely to emerge after five times sequential passages through treatment with PF-429242. Although the levels of intracellular cholesterol and lipid droplets were reduced by PF-429242, viral propagations were not recovered by addition of exogenous cholesterol or fatty acids, indicating that the reduction of LD and cholesterol caused by PF-429242 treatment is not related to its mechanism of action against DENV propagation. Our results suggest that PF-429242 is a promising candidate for an anti-DENV agent. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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Review
Viruses Causing Gastroenteritis: The Known, The New and Those Beyond
by Bas B. Oude Munnink and Lia Van der Hoek
Viruses 2016, 8(2), 42; https://doi.org/10.3390/v8020042 - 8 Feb 2016
Cited by 72 | Viewed by 10504
Abstract
The list of recently discovered gastrointestinal viruses is expanding rapidly. Whether these agents are actually involved in a disease such as diarrhea is the essential question, yet difficult to answer. In this review a summary of all viruses found in diarrhea is presented, [...] Read more.
The list of recently discovered gastrointestinal viruses is expanding rapidly. Whether these agents are actually involved in a disease such as diarrhea is the essential question, yet difficult to answer. In this review a summary of all viruses found in diarrhea is presented, together with the current knowledge about their connection to disease. Full article
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Review
Big Data Offers Novel Insights for Oncolytic Virus Immunotherapy
by Stephanie L. Swift and David F. Stojdl
Viruses 2016, 8(2), 45; https://doi.org/10.3390/v8020045 - 5 Feb 2016
Cited by 12 | Viewed by 7935
Abstract
Large-scale assays, such as microarrays, next-generation sequencing and various “omics” technologies, have explored multiple aspects of the immune response following virus infection, often from a public health perspective. Yet a lack of similar data exists for monitoring immune engagement during oncolytic virus immunotherapy [...] Read more.
Large-scale assays, such as microarrays, next-generation sequencing and various “omics” technologies, have explored multiple aspects of the immune response following virus infection, often from a public health perspective. Yet a lack of similar data exists for monitoring immune engagement during oncolytic virus immunotherapy (OVIT) in the cancer setting. Tracking immune signatures at the tumour site can create a snapshot or longitudinally analyse immune cell activation, infiltration and functionality within global populations or individual cells. Mapping immune changes over the course of oncolytic biotherapy—from initial infection to tumour stabilisation/regression through to long-term cure or escape/relapse—has the potential to generate important therapeutic insights around virus-host interactions. Further, correlating such immune signatures with specific tumour outcomes has significant value for guiding the development of novel oncolytic virus immunotherapy strategies. Here, we provide insights for OVIT from large-scale analyses of immune populations in the infection, vaccination and immunotherapy setting. We analyse several approaches to manipulating immune engagement during OVIT. We further explore immunocentric changes in the tumour tissue following immunotherapy, and compile several immune signatures of therapeutic success. Ultimately, we highlight clinically relevant large-scale approaches with the potential to strengthen future oncolytic strategies to optimally engage the immune system. Full article
(This article belongs to the Special Issue Oncolytic Viruses)
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Article
A KDEL Retrieval System for ER-Golgi Transport of Japanese Encephalitis Viral Particles
by Robert YL Wang, Yu-Jen Wu, Han-Shan Chen and Chih-Jung Chen
Viruses 2016, 8(2), 44; https://doi.org/10.3390/v8020044 - 5 Feb 2016
Cited by 10 | Viewed by 7221
Abstract
Evidence has emerged that RNA viruses utilize the host secretory pathway for processing and trafficking mature viral particles and for exiting the infected cells. Upon completing the complex assembly process, the viral particles take advantage of the cellular secretory trafficking machinery for their [...] Read more.
Evidence has emerged that RNA viruses utilize the host secretory pathway for processing and trafficking mature viral particles and for exiting the infected cells. Upon completing the complex assembly process, the viral particles take advantage of the cellular secretory trafficking machinery for their intracellular trafficking toward the Golgi organelle and budding or export of virions. In this study, we showed that Japanese encephalitis virus (JEV)-induced extracellular GRP78 contains no KDEL motif using an anti-KDEL-specific antibody. Overexpression of the KDEL-truncated GRP78 in the GPR78 knocked down cells significantly reduced JEV infectivity, suggesting that the KDEL motif is required for GRP78 function in the release of JE viral particles. In addition, we demonstrated the KDELR protein, an ER-Golgi retrieval system component, is associated with viral envelope proteins and is engaged in the subcellular localization of viral particles in Golgi. More importantly, accumulation of intracellular virions was observed in the KDELR knocked down cells, indicating that the KDELR protein mediated the intracellular trafficking of JE viral particles. Altogether, we demonstrated that intracellular trafficking of JE assembled viral particles was mediated by the host ER-Golgi retrieval system prior to exit by the secretory pathway. Full article
(This article belongs to the Special Issue Host Membranes and the Viral Infection Cycle)
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Review
To Infection and Beyond: The Multi-Pronged Anti-Cancer Mechanisms of Oncolytic Viruses
by Kevin A. Cassady, Kellie B. Haworth, Josh Jackson, James M. Markert and Timothy P. Cripe
Viruses 2016, 8(2), 43; https://doi.org/10.3390/v8020043 - 4 Feb 2016
Cited by 38 | Viewed by 10058
Abstract
Over the past 1–2 decades we have witnessed a resurgence of efforts to therapeutically exploit the attributes of lytic viruses to infect and kill tumor cells while sparing normal cells. We now appreciate that the utility of viruses for treating cancer extends far [...] Read more.
Over the past 1–2 decades we have witnessed a resurgence of efforts to therapeutically exploit the attributes of lytic viruses to infect and kill tumor cells while sparing normal cells. We now appreciate that the utility of viruses for treating cancer extends far beyond lytic cell death. Viruses are also capable of eliciting humoral and cellular innate and adaptive immune responses that may be directed not only at virus-infected cells but also at uninfected cancer cells. Here we review our current understanding of this bystander effect, and divide the mechanisms into lytic, cytokine, innate cellular, and adaptive phases. Knowing the key pathways and molecular players during virus infection in the context of the cancer microenvironment will be critical to devise strategies to maximize the therapeutic effects of oncolytic viroimmunotherapy. Full article
(This article belongs to the Special Issue Oncolytic Viruses)
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Article
Generation of Recombinant Polioviruses Harboring RNA Affinity Tags in the 5′ and 3′ Noncoding Regions of Genomic RNAs
by Dylan Flather, Andrea L. Cathcart, Casey Cruz, Eric Baggs, Tuan Ngo, Paul D. Gershon and Bert L. Semler
Viruses 2016, 8(2), 39; https://doi.org/10.3390/v8020039 - 4 Feb 2016
Cited by 4 | Viewed by 7026
Abstract
Despite being intensely studied for more than 50 years, a complete understanding of the enterovirus replication cycle remains elusive. Specifically, only a handful of cellular proteins have been shown to be involved in the RNA replication cycle of these viruses. In an effort [...] Read more.
Despite being intensely studied for more than 50 years, a complete understanding of the enterovirus replication cycle remains elusive. Specifically, only a handful of cellular proteins have been shown to be involved in the RNA replication cycle of these viruses. In an effort to isolate and identify additional cellular proteins that function in enteroviral RNA replication, we have generated multiple recombinant polioviruses containing RNA affinity tags within the 3′ or 5′ noncoding region of the genome. These recombinant viruses retained RNA affinity sequences within the genome while remaining viable and infectious over multiple passages in cell culture. Further characterization of these viruses demonstrated that viral protein production and growth kinetics were unchanged or only slightly altered relative to wild type poliovirus. However, attempts to isolate these genetically-tagged viral genomes from infected cells have been hindered by high levels of co-purification of nonspecific proteins and the limited matrix-binding efficiency of RNA affinity sequences. Regardless, these recombinant viruses represent a step toward more thorough characterization of enterovirus ribonucleoprotein complexes involved in RNA replication. Full article
(This article belongs to the Special Issue Recent Progress in Enterovirus Research)
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Article
A Potential of an Anti-HTLV-I gp46 Neutralizing Monoclonal Antibody (LAT-27) for Passive Immunization against Both Horizontal and Mother-to-Child Vertical Infection with Human T Cell Leukemia Virus Type-I
by Hideki Fujii, Mamoru Shimizu, Takuya Miyagi, Marie Kunihiro, Reiko Tanaka, Yoshiaki Takahashi and Yuetsu Tanaka
Viruses 2016, 8(2), 41; https://doi.org/10.3390/v8020041 - 3 Feb 2016
Cited by 15 | Viewed by 5730
Abstract
Although the number of human T-cell leukemia virus type-I (HTLV-I)-infected individuals in the world has been estimated at over 10 million, no prophylaxis vaccines against HTLV-I infection are available. In this study, we took a new approach for establishing the basis of protective [...] Read more.
Although the number of human T-cell leukemia virus type-I (HTLV-I)-infected individuals in the world has been estimated at over 10 million, no prophylaxis vaccines against HTLV-I infection are available. In this study, we took a new approach for establishing the basis of protective vaccines against HTLV-I. We show here the potential of a passively administered HTLV-I neutralizing monoclonal antibody of rat origin (LAT-27) that recognizes epitopes consisting of the HTLV-I gp46 amino acids 191–196. LAT-27 completely blocked HTLV-I infection in vitro at a minimum concentration of 5 μg/mL. Neonatal rats born to mother rats pre-infused with LAT-27 were shown to have acquired a large quantity of LAT-27, and these newborns showed complete resistance against intraperitoneal infection with HTLV-I. On the other hand, when humanized immunodeficient mice were pre-infused intravenously with humanized LAT-27 (hu-LAT-27), all the mice completely resisted HTLV-I infection. These results indicate that hu-LAT-27 may have a potential for passive immunization against both horizontal and mother-to-child vertical infection with HTLV-I. Full article
(This article belongs to the Special Issue Recent Advances in HTLV Research 2015)
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Review
Mother-to-Child Transmission of HTLV-1 Epidemiological Aspects, Mechanisms and Determinants of Mother-to-Child Transmission
by Florent Percher, Patricia Jeannin, Sandra Martin-Latil, Antoine Gessain, Philippe V. Afonso, Aurore Vidy-Roche and Pierre-Emmanuel Ceccaldi
Viruses 2016, 8(2), 40; https://doi.org/10.3390/v8020040 - 3 Feb 2016
Cited by 73 | Viewed by 9137
Abstract
Human T-cell Lymphotropic Virus type 1 (HTLV-1) is a human retrovirus that infects at least 5–10 million people worldwide, and is the etiological agent of a lymphoproliferative malignancy; Adult T-cell Leukemia/Lymphoma (ATLL); and a chronic neuromyelopathy, HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), as [...] Read more.
Human T-cell Lymphotropic Virus type 1 (HTLV-1) is a human retrovirus that infects at least 5–10 million people worldwide, and is the etiological agent of a lymphoproliferative malignancy; Adult T-cell Leukemia/Lymphoma (ATLL); and a chronic neuromyelopathy, HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), as well as other inflammatory diseases such as infective dermatitis and uveitis. Besides sexual intercourse and intravenous transmission, HTLV-1 can also be transmitted from infected mother to child during prolonged breastfeeding. Some characteristics that are linked to mother-to-child transmission (MTCT) of HTLV-1, such as the role of proviral load, antibody titer of the infected mother, and duration of breastfeeding, have been elucidated; however, most of the mechanisms underlying HTLV-1 transmission during breast feeding remain largely unknown, such as the sites of infection and cellular targets as well as the role of milk factors. The present review focuses on the latest findings and current opinions and perspectives on MTCT of HTLV-1. Full article
(This article belongs to the Special Issue Recent Advances in HTLV Research 2015)
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Review
Genetic Markers of the Host in Persons Living with HTLV-1, HIV and HCV Infections
by Tatiane Assone, Arthur Paiva, Luiz Augusto M. Fonseca and Jorge Casseb
Viruses 2016, 8(2), 38; https://doi.org/10.3390/v8020038 - 3 Feb 2016
Cited by 14 | Viewed by 6706
Abstract
Human T-cell leukemia virus type 1 (HTLV-1), hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) are prevalent worldwide, and share similar means of transmission. These infections may influence each other in evolution and outcome, including cancer or immunodeficiency. Many studies [...] Read more.
Human T-cell leukemia virus type 1 (HTLV-1), hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) are prevalent worldwide, and share similar means of transmission. These infections may influence each other in evolution and outcome, including cancer or immunodeficiency. Many studies have reported the influence of genetic markers on the host immune response against different persistent viral infections, such as HTLV-1 infection, pointing to the importance of the individual genetic background on their outcomes. However, despite recent advances on the knowledge of the pathogenesis of HTLV-1 infection, gaps in the understanding of the role of the individual genetic background on the progress to disease clinically manifested still remain. In this scenario, much less is known regarding the influence of genetic factors in the context of dual or triple infections or their influence on the underlying mechanisms that lead to outcomes that differ from those observed in monoinfection. This review describes the main factors involved in the virus–host balance, especially for some particular human leukocyte antigen (HLA) haplotypes, and other important genetic markers in the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other persistent viruses, such as HIV and HCV. Full article
(This article belongs to the Special Issue Recent Advances in HTLV Research 2015)
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Article
Adenovirus E1A/E1B Transformed Amniotic Fluid Cells Support Human Cytomegalovirus Replication
by Natascha Krömmelbein, Lüder Wiebusch, Gudrun Schiedner, Nicole Büscher, Caroline Sauer, Luise Florin, Elisabeth Sehn, Uwe Wolfrum and Bodo Plachter
Viruses 2016, 8(2), 37; https://doi.org/10.3390/v8020037 - 2 Feb 2016
Cited by 12 | Viewed by 7505
Abstract
The human cytomegalovirus (HCMV) replicates to high titers in primary human fibroblast cell cultures. A variety of primary human cells and some tumor-derived cell lines do also support permissive HCMV replication, yet at low levels. Cell lines established by transfection of the transforming [...] Read more.
The human cytomegalovirus (HCMV) replicates to high titers in primary human fibroblast cell cultures. A variety of primary human cells and some tumor-derived cell lines do also support permissive HCMV replication, yet at low levels. Cell lines established by transfection of the transforming functions of adenoviruses have been notoriously resistant to HCMV replication and progeny production. Here, we provide first-time evidence that a permanent cell line immortalized by adenovirus type 5 E1A and E1B (CAP) is supporting the full HCMV replication cycle and is releasing infectious progeny. The CAP cell line had previously been established from amniotic fluid cells which were likely derived from membranes of the developing fetus. These cells can be grown under serum-free conditions. HCMV efficiently penetrated CAP cells, expressed its immediate-early proteins and dispersed restrictive PML-bodies. Viral DNA replication was initiated and viral progeny became detectable by electron microscopy in CAP cells. Furthermore, infectious virus was released from CAP cells, yet to lower levels compared to fibroblasts. Subviral dense bodies were also secreted from CAP cells. The results show that E1A/E1B expression in transformed cells is not generally repressive to HCMV replication and that CAP cells may be a good substrate for dense body based vaccine production. Full article
(This article belongs to the Section Animal Viruses)
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Article
Begomovirus-Associated Satellite DNA Diversity Captured Through Vector-Enabled Metagenomic (VEM) Surveys Using Whiteflies (Aleyrodidae)
by Karyna Rosario, Christian Marr, Arvind Varsani, Simona Kraberger, Daisy Stainton, Enrique Moriones, Jane E. Polston and Mya Breitbart
Viruses 2016, 8(2), 36; https://doi.org/10.3390/v8020036 - 2 Feb 2016
Cited by 37 | Viewed by 8415
Abstract
Monopartite begomoviruses (Geminiviridae), which are whitefly-transmitted single-stranded DNA viruses known for causing devastating crop diseases, are often associated with satellite DNAs. Since begomovirus acquisition or exchange of satellite DNAs may lead to adaptation to new plant hosts and emergence of new [...] Read more.
Monopartite begomoviruses (Geminiviridae), which are whitefly-transmitted single-stranded DNA viruses known for causing devastating crop diseases, are often associated with satellite DNAs. Since begomovirus acquisition or exchange of satellite DNAs may lead to adaptation to new plant hosts and emergence of new disease complexes, it is important to investigate the diversity and distribution of these molecules. This study reports begomovirus-associated satellite DNAs identified during a vector-enabled metagenomic (VEM) survey of begomoviruses using whiteflies collected in various locations (California (USA), Guatemala, Israel, Puerto Rico, and Spain). Protein-encoding satellite DNAs, including alphasatellites and betasatellites, were identified in Israel, Puerto Rico, and Guatemala. Novel alphasatellites were detected in samples from Guatemala and Puerto Rico, resulting in the description of a phylogenetic clade (DNA-3-type alphasatellites) dominated by New World sequences. In addition, a diversity of small (~640–750 nucleotides) satellite DNAs similar to satellites associated with begomoviruses infecting Ipomoea spp. were detected in Puerto Rico and Spain. A third class of satellite molecules, named gammasatellites, is proposed to encompass the increasing number of reported small (<1 kilobase), non-coding begomovirus-associated satellite DNAs. This VEM-based survey indicates that, although recently recovered begomovirus genomes are variations of known genetic themes, satellite DNAs hold unexplored genetic diversity. Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
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Article
Metagenomic Analysis of Virioplankton of the Subtropical Jiulong River Estuary, China
by Lanlan Cai, Rui Zhang, Ying He, Xiaoyuan Feng and Nianzhi Jiao
Viruses 2016, 8(2), 35; https://doi.org/10.3390/v8020035 - 2 Feb 2016
Cited by 42 | Viewed by 8222
Abstract
Viruses are the most abundant biological entities in the oceans, and encompass a significant reservoir of genetic diversity. However, little is known about their biodiversity in estuary environments, which represent a highly dynamic and potentially more diverse habitat. Here, we report a metagenomic [...] Read more.
Viruses are the most abundant biological entities in the oceans, and encompass a significant reservoir of genetic diversity. However, little is known about their biodiversity in estuary environments, which represent a highly dynamic and potentially more diverse habitat. Here, we report a metagenomic analysis of the dsDNA viral community from the Jiulong River Estuary (JRE), China, and provide a comparative analysis with other closely related environments. The results showed that the majority of JRE virome did not show any significant similarity to the database. For the major viral group (Caudovirales) detected in the sample, Podoviridae (44.88%) were the most abundant family, followed by Siphoviridae (32.98%) and Myoviridae (17.32%). The two most abundant viruses identified in the virome were phages HTVC010P and HMO-2011, which infect bacteria belonging to marine SAR11 and SAR116 clades, respectively. Two contigs larger than 20 kb, which show similar overall genome architectures to Celeribacter phage P12053L and Thalosomonas phage BA3, respectively, were generated during assembly. Comparative analysis showed that the JRE virome was more similar to marine viromes than to freshwater viromes, and shared a relative coarse-grain genetic overlap (averaging 14.14% ± 1.68%) with other coastal viromes. Our study indicated that the diversity and community structure of the virioplankton found in JRE were mainly affected by marine waters, with less influence from freshwater discharge. Full article
(This article belongs to the Special Issue Next Generation Sequencing: New Developments and Discoveries in Virology)
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Review
The Role of HBZ in HTLV-1-Induced Oncogenesis
by Tiejun Zhao
Viruses 2016, 8(2), 34; https://doi.org/10.3390/v8020034 - 2 Feb 2016
Cited by 40 | Viewed by 6415
Abstract
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and chronic inflammatory diseases. HTLV-1 bZIP factor (HBZ) is transcribed as an antisense transcript of the HTLV-1 provirus. Among the HTLV-1-encoded viral genes, HBZ is the only gene that is constitutively [...] Read more.
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and chronic inflammatory diseases. HTLV-1 bZIP factor (HBZ) is transcribed as an antisense transcript of the HTLV-1 provirus. Among the HTLV-1-encoded viral genes, HBZ is the only gene that is constitutively expressed in all ATL cases. Recent studies have demonstrated that HBZ plays an essential role in oncogenesis by regulating viral transcription and modulating multiple host factors, as well as cellular signaling pathways, that contribute to the development and continued growth of cancer. In this article, I summarize the current knowledge of the oncogenic function of HBZ in cell proliferation, apoptosis, T-cell differentiation, immune escape, and HTLV-1 pathogenesis. Full article
(This article belongs to the Special Issue Recent Advances in HTLV Research 2015)
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Article
Pandemic Influenza A (H1N1) Virus Infection Increases Apoptosis and HIV-1 Replication in HIV-1 Infected Jurkat Cells
by Xue Wang, Jiying Tan, Santanu Biswas, Jiangqin Zhao, Krishnakumar Devadas, Zhiping Ye and Indira Hewlett
Viruses 2016, 8(2), 33; https://doi.org/10.3390/v8020033 - 2 Feb 2016
Cited by 9 | Viewed by 5833
Abstract
Influenza virus infection has a significant impact on public health, since it is a major cause of morbidity and mortality. It is not well-known whether influenza virus infection affects cell death and human immunodeficiency virus (HIV)-1 replication in HIV-1-infected patients. Using a lymphoma [...] Read more.
Influenza virus infection has a significant impact on public health, since it is a major cause of morbidity and mortality. It is not well-known whether influenza virus infection affects cell death and human immunodeficiency virus (HIV)-1 replication in HIV-1-infected patients. Using a lymphoma cell line, Jurkat, we examined the in vitro effects of pandemic influenza A (H1N1) virus (pH1N1) infection on cell death and HIV-1 RNA production in infected cells. We found that pH1N1 infection increased apoptotic cell death through Fas and Bax-mediated pathways in HIV-1-infected Jurkat cells. Infection with pH1N1 virus could promote HIV-1 RNA production by activating host transcription factors including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), nuclear factor of activated T-cells (NFAT) and activator protein 1 (AP-1) through mitogen-activated protein kinases (MAPK) pathways and T-cell antigen receptor (TCR)-related pathways. The replication of HIV-1 latent infection could be reactivated by pH1N1 infection through TCR and apoptotic pathways. These data indicate that HIV-1 replication can be activated by pH1N1 virus in HIV-1-infected cells resulting in induction of cell death through apoptotic pathways. Full article
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Review
The Autophagic Machinery in Enterovirus Infection
by Jeffrey K. F. Lai, I-Ching Sam and Yoke Fun Chan
Viruses 2016, 8(2), 32; https://doi.org/10.3390/v8020032 - 27 Jan 2016
Cited by 28 | Viewed by 11133
Abstract
The Enterovirus genus of the Picornaviridae family comprises many important human pathogens, including polioviruses, rhinovirus, enterovirus A71, and enterovirus D68. They cause a wide variety of diseases, ranging from mild to severe life-threatening diseases. Currently, no effective vaccine is available against enteroviruses except [...] Read more.
The Enterovirus genus of the Picornaviridae family comprises many important human pathogens, including polioviruses, rhinovirus, enterovirus A71, and enterovirus D68. They cause a wide variety of diseases, ranging from mild to severe life-threatening diseases. Currently, no effective vaccine is available against enteroviruses except for poliovirus. Enteroviruses subvert the autophagic machinery to benefit their assembly, maturation, and exit from host. Some enteroviruses spread between cells via a process described as autophagosome-mediated exit without lysis (AWOL). The early and late phases of autophagy are regulated through various lipids and their metabolizing enzymes. Some of these lipids and enzymes are specifically regulated by enteroviruses. In the present review, we summarize the current understanding of the regulation of autophagic machinery by enteroviruses, and provide updates on recent developments in this field. Full article
(This article belongs to the Special Issue Recent Progress in Enterovirus Research)
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Review
Molecular Studies of HTLV-1 Replication: An Update
by Jessica L. Martin, José O. Maldonado, Joachim D. Mueller, Wei Zhang and Louis M. Mansky
Viruses 2016, 8(2), 31; https://doi.org/10.3390/v8020031 - 27 Jan 2016
Cited by 50 | Viewed by 14353
Abstract
Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus discovered. Studies on HTLV-1 have been instrumental for our understanding of the molecular pathology of virus-induced cancers. HTLV-1 is the etiological agent of an adult T-cell leukemia (ATL) and can lead [...] Read more.
Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus discovered. Studies on HTLV-1 have been instrumental for our understanding of the molecular pathology of virus-induced cancers. HTLV-1 is the etiological agent of an adult T-cell leukemia (ATL) and can lead to a variety of neurological pathologies, including HTLV-1-associated-myelopathy/tropical spastic paraparesis (HAM/TSP). The ability to treat the aggressive ATL subtypes remains inadequate. HTLV-1 replicates by (1) an infectious cycle involving virus budding and infection of new permissive target cells and (2) mitotic division of cells harboring an integrated provirus. Virus replication initiates host antiviral immunity and the checkpoint control of cell proliferation, but HTLV-1 has evolved elegant strategies to counteract these host defense mechanisms to allow for virus persistence. The study of the molecular biology of HTLV-1 replication has provided crucial information for understanding HTLV-1 replication as well as aspects of viral replication that are shared between HTLV-1 and human immunodeficiency virus type 1 (HIV-1). Here in this review, we discuss the various stages of the virus replication cycle—both foundational knowledge as well as current updates of ongoing research that is important for understanding HTLV-1 molecular pathogenesis as well as in developing novel therapeutic strategies. Full article
(This article belongs to the Special Issue Recent Advances in HTLV Research 2015)
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Editorial
Testing New Hypotheses Regarding Ebolavirus Reservoirs
by Siv Aina Jensen Leendertz
Viruses 2016, 8(2), 30; https://doi.org/10.3390/v8020030 - 26 Jan 2016
Cited by 33 | Viewed by 10546
Abstract
Despite a relatively long search for the origin of ebolaviruses, their reservoirs remain elusive. Researchers might have to consider testing alternative hypotheses about how these viruses persist and emerge to advance ebolavirus research. This article aims to encourage researchers to bring forward such [...] Read more.
Despite a relatively long search for the origin of ebolaviruses, their reservoirs remain elusive. Researchers might have to consider testing alternative hypotheses about how these viruses persist and emerge to advance ebolavirus research. This article aims to encourage researchers to bring forward such hypotheses, to discuss them scientifically and to open alternative research avenues regarding the origin and ecology of ebolaviruses. Full article
(This article belongs to the Collection Advances in Ebolavirus, Marburgvirus, and Cuevavirus Research)
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Article
HPV Population Profiling in Healthy Men by Next-Generation Deep Sequencing Coupled with HPV-QUEST
by Li Yin, Jin Yao, Kaifen Chang, Brent P. Gardner, Fahong Yu, Anna R. Giuliano and Maureen M. Goodenow
Viruses 2016, 8(2), 28; https://doi.org/10.3390/v8020028 - 25 Jan 2016
Cited by 8 | Viewed by 8590
Abstract
Multiple-type human papillomaviruses (HPV) infection presents a greater risk for persistence in asymptomatic individuals and may accelerate cancer development. To extend the scope of HPV types defined by probe-based assays, multiplexing deep sequencing of HPV L1, coupled with an HPV-QUEST genotyping server and [...] Read more.
Multiple-type human papillomaviruses (HPV) infection presents a greater risk for persistence in asymptomatic individuals and may accelerate cancer development. To extend the scope of HPV types defined by probe-based assays, multiplexing deep sequencing of HPV L1, coupled with an HPV-QUEST genotyping server and a bioinformatic pipeline, was established and applied to survey the diversity of HPV genotypes among a subset of healthy men from the HPV in Men (HIM) Multinational Study. Twenty-one HPV genotypes (12 high-risk and 9 low-risk) were detected in the genital area from 18 asymptomatic individuals. A single HPV type, either HPV16, HPV6b or HPV83, was detected in 7 individuals, while coinfection by 2 to 5 high-risk and/or low-risk genotypes was identified in the other 11 participants. In two individuals studied for over one year, HPV16 persisted, while fluctuations of coinfecting genotypes occurred. HPV L1 regions were generally identical between query and reference sequences, although nonsynonymous and synonymous nucleotide polymorphisms of HPV16, 18, 31, 35h, 59, 70, 73, cand85, 6b, 62, 81, 83, cand89 or JEB2 L1 genotypes, mostly unidentified by linear array, were evident. Deep sequencing coupled with HPV-QUEST provides efficient and unambiguous classification of HPV genotypes in multiple-type HPV infection in host ecosystems. Full article
(This article belongs to the Special Issue Next Generation Sequencing: New Developments and Discoveries in Virology)
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Article
Experimental Inoculation of Egyptian Fruit Bats (Rousettus aegyptiacus) with Ebola Virus
by Janusz T. Paweska, Nadia Storm, Antoinette A. Grobbelaar, Wanda Markotter, Alan Kemp and Petrus Jansen van Vuren
Viruses 2016, 8(2), 29; https://doi.org/10.3390/v8020029 - 22 Jan 2016
Cited by 60 | Viewed by 8802
Abstract
Colonized Egyptian fruit bats (Rousettus aegyptiacus), originating in South Africa, were inoculated subcutaneously with Ebola virus (EBOV). No overt signs of morbidity, mortality, or gross lesions were noted. Bats seroconverted by Day 10–16 post inoculation (p.i.), with the highest mean anti-EBOV [...] Read more.
Colonized Egyptian fruit bats (Rousettus aegyptiacus), originating in South Africa, were inoculated subcutaneously with Ebola virus (EBOV). No overt signs of morbidity, mortality, or gross lesions were noted. Bats seroconverted by Day 10–16 post inoculation (p.i.), with the highest mean anti-EBOV IgG level on Day 28 p.i. EBOV RNA was detected in blood from one bat. In 16 other tissues tested, viral RNA distribution was limited and at very low levels. No seroconversion could be demonstrated in any of the control bats up to 28 days after in-contact exposure to subcutaneously-inoculated bats. The control bats were subsequently inoculated intraperitoneally, and intramuscularly with the same dose of EBOV. No mortality, morbidity or gross pathology was observed in these bats. Kinetics of immune response was similar to that in subcutaneously-inoculated bats. Viral RNA was more widely disseminated to multiple tissues and detectable in a higher proportion of individuals, but consistently at very low levels. Irrespective of the route of inoculation, no virus was isolated from tissues which tested positive for EBOV RNA. Viral RNA was not detected in oral, nasal, ocular, vaginal, penile and rectal swabs from any of the experimental groups. Full article
(This article belongs to the Collection Advances in Ebolavirus, Marburgvirus, and Cuevavirus Research)
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