Viruses

Research

20 pages, 3078 KiB

Open AccessArticle

Functional Analyses of Bovine Foamy Virus-Encoded miRNAs Reveal the Importance of a Defined miRNA for Virus Replication and Host–Virus Interaction

by Wenhu Cao, Erik Stricker, Agnes Hotz-Wagenblatt, Anke Heit-Mondrzyk, Georgios Pougialis, Annette Hugo, Jacek Kuźmak, Magdalena Materniak-Kornas and Martin Löchelt

Viruses 2020, 12(11), 1250; https://doi.org/10.3390/v12111250 - 2 Nov 2020

Cited by 14 | Viewed by 2519

Abstract

In addition to regulatory or accessory proteins, some complex retroviruses gain a repertoire of micro-RNAs (miRNAs) to regulate and control virus–host interactions for efficient replication and spread. In particular, bovine and simian foamy viruses (BFV and SFV) have recently been shown to express [...] Read more.

In addition to regulatory or accessory proteins, some complex retroviruses gain a repertoire of micro-RNAs (miRNAs) to regulate and control virus–host interactions for efficient replication and spread. In particular, bovine and simian foamy viruses (BFV and SFV) have recently been shown to express a diverse set of RNA polymerase III-directed miRNAs, some with a unique primary miRNA double-hairpin, dumbbell-shaped structure not known in other viruses or organisms. While the mechanisms of expression and structural requirements have been studied, the functional importance of these miRNAs is still far from understood. Here, we describe the in silico identification of BFV miRNA targets and the subsequent experimental validation of bovine Ankyrin Repeat Domain 17 (ANKRD17) and Bax-interacting factor 1 (Bif1) target genes in vitro and, finally, the suppression of ANKRD17 downstream genes in the affected pathway. Deletion of the entire miRNA cassette in the non-coding part of the U3 region of the long terminal repeats attenuated replication of corresponding BFV mutants in bovine cells. This repression can be almost completely trans-complemented by the most abundant miRNA BF2-5p having the best scores for predicted and validated BFV miRNA target genes. Deletion of the miRNA cassette does not grossly affect particle release and overall particle composition. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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16 pages, 1473 KiB

Open AccessArticle

Genome Analysis and Replication Studies of the African Green Monkey Simian Foamy Virus Serotype 3 Strain FV2014

by Sandra M. Fuentes, Eunhae H. Bae, Subhiksha Nandakumar, Dhanya K. Williams and Arifa S. Khan

Viruses 2020, 12(4), 403; https://doi.org/10.3390/v12040403 - 6 Apr 2020

Cited by 1 | Viewed by 2679

Abstract

African green monkey (AGM) spumaretroviruses have been less well-studied than other simian foamy viruses (SFVs). We report the biological and genomic characterization of SFVcae_FV2014, which was the first foamy virus isolated from an African green monkey (AGM) and was found to be serotype [...] Read more.

African green monkey (AGM) spumaretroviruses have been less well-studied than other simian foamy viruses (SFVs). We report the biological and genomic characterization of SFVcae_FV2014, which was the first foamy virus isolated from an African green monkey (AGM) and was found to be serotype 3. Infectivity studies in various cell lines from different species (mouse, dog, rhesus monkey, AGM, and human) indicated that like other SFVs, SFVcae_FV2014 had broad species and cell tropism, and in vitro cell culture infection resulted in cytopathic effect (CPE). In Mus dunni (a wild mouse fibroblast cell line), MDCK (Madin-Darby canine kidney cell line), FRhK-4 (a fetal rhesus kidney cell line), and MRC-5 (a human fetal lung cell line), SFVcae_FV2014 infection was productive resulting in CPE, and had delayed or similar replication kinetics compared with SFVmcy_FV21 and SFVmcy_FV34[RF], which are two Taiwanese macaque isolates, designated as serotypes 1 and 2, respectively. However, in Vero (AGM kidney cell line) and A549 (a human lung carcinoma cell line), the replication kinetics of SFVcae_FV2014 and the SFVmcy viruses were discordant: In Vero, SFVcae_FV2014 showed rapid replication kinetics and extensive CPE, and a persistent infection was seen in A549, with delayed, low CPE, which did not progress even upon extended culture (day 55). Nucleotide sequence analysis of the assembled SFVcae_FV2014 genome, obtained by high-throughput sequencing, indicated an overall 80–90% nucleotide sequence identity with SFVcae_LK3, the only available full-length genome sequence of an AGM SFV, and was distinct phylogenetically from other AGM spumaretroviruses, corroborating previous results based on analysis of partial env sequences. Our study confirmed that SFVcae_FV2014 and SFVcae_LK3 are genetically distinct AGM foamy virus (FV) isolates. Furthermore, comparative infectivity studies of SFVcae_FV2014 and SFVmcy isolates showed that although SFVs have a wide host range and cell tropism, regulation of virus replication is complex and depends on the virus strain and cell-specific factors. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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15 pages, 2977 KiB

Open AccessArticle

Infection with Foamy Virus in Wild Ruminants—Evidence for a New Virus Reservoir?

by Magdalena Materniak-Kornas, Martin Löchelt, Jerzy Rola and Jacek Kuźmak

Viruses 2020, 12(1), 58; https://doi.org/10.3390/v12010058 - 3 Jan 2020

Cited by 2 | Viewed by 2564

Abstract

Foamy viruses (FVs) are widely distributed and infect many animal species including non-human primates, horses, cattle, and cats. Several reports also suggest that other species can be FV hosts. Since most of such studies involved livestock or companion animals, we aimed to test [...] Read more.

Foamy viruses (FVs) are widely distributed and infect many animal species including non-human primates, horses, cattle, and cats. Several reports also suggest that other species can be FV hosts. Since most of such studies involved livestock or companion animals, we aimed to test blood samples from wild ruminants for the presence of FV-specific antibodies and, subsequently, genetic material. Out of 269 serum samples tested by ELISA with the bovine foamy virus (BFV) Gag and Bet antigens, 23 sera showed increased reactivity to at least one of them. High reactive sera represented 30% of bison samples and 7.5% of deer specimens. Eleven of the ELISA-positives were also strongly positive in immunoblot analyses. The peripheral blood DNA of seroreactive animals was tested by semi-nested PCR. The specific 275 bp fragment of the pol gene was amplified only in one sample collected from a red deer and the analysis of its sequence showed the highest homology for European BFV isolates. Such results may suggest the existence of a new FV reservoir in bison as well as in deer populations. Whether the origin of such infections stems from a new FV or is the result of BFV inter-species transmission remains to be clarified. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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20 pages, 4820 KiB

Open AccessArticle

Insights into Innate Sensing of Prototype Foamy Viruses in Myeloid Cells

by Maïwenn Bergez, Jakob Weber, Maximilian Riess, Alexander Erdbeer, Janna Seifried, Nicole Stanke, Clara Munz, Veit Hornung, Renate König and Dirk Lindemann

Viruses 2019, 11(12), 1095; https://doi.org/10.3390/v11121095 - 26 Nov 2019

Cited by 5 | Viewed by 3755

Abstract

Foamy viruses (FVs) belong to the Spumaretrovirinae subfamily of retroviruses and are characterized by unique features in their replication strategy. This includes a reverse transcription (RTr) step of the packaged RNA genome late in replication, resulting in the release of particles with a [...] Read more.

Foamy viruses (FVs) belong to the Spumaretrovirinae subfamily of retroviruses and are characterized by unique features in their replication strategy. This includes a reverse transcription (RTr) step of the packaged RNA genome late in replication, resulting in the release of particles with a fraction of them already containing an infectious viral DNA (vDNA) genome. Little is known about the immune responses against FVs in their hosts, which control infection and may be responsible for their apparent apathogenic nature. We studied the interaction of FVs with the innate immune system in myeloid cells, and characterized the viral pathogen-associated molecular patterns (PAMPs) and the cellular pattern recognition receptors and sensing pathways involved. Upon cytoplasmic access, full-length but not minimal vector genome containing FVs with active reverse transcriptase, induced an efficient innate immune response in various myeloid cells. It was dependent on cellular cGAS and STING and largely unaffected by RTr inhibition during viral entry. This suggests that RTr products, which are generated during FV morphogenesis in infected cells, and are therefore already present in FV particles taken up by immune cells, are the main PAMPs of FVs with full-length genomes sensed in a cGAS and STING-dependent manner by the innate immune system in host cells of the myeloid lineage. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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13 pages, 2594 KiB

Open AccessArticle

Eco-Epidemiological Profile and Molecular Characterization of Simian Foamy Virus in a Recently-Captured Invasive Population of Leontopithecus chrysomelas (Golden-Headed Lion Tamarin) in Rio de Janeiro, Brazil

by Thamiris S. Miranda, Cláudia P. Muniz, Silvia B. Moreira, Marina G. Bueno, Maria Cecília M. Kierulff, Camila V. Molina, José L. Catão-Dias, Alcides Pissinatti, Marcelo A. Soares and André F. Santos

Viruses 2019, 11(10), 931; https://doi.org/10.3390/v11100931 - 10 Oct 2019

Cited by 2 | Viewed by 2610

Abstract

Simian foamy viruses (SFV) infect a wide range of Old World and Neotropical primates (NP). Unlike Old World primates, little is known about the diversity and prevalence of SFV in NP, mainly from a free-living population. Phylogenetic analyses have shown that SFV coevolved [...] Read more.

Simian foamy viruses (SFV) infect a wide range of Old World and Neotropical primates (NP). Unlike Old World primates, little is known about the diversity and prevalence of SFV in NP, mainly from a free-living population. Phylogenetic analyses have shown that SFV coevolved with their hosts. However, viral strains infecting Leontopithecus chrysomelas did not behave as expected for this hypothesis. The purpose of this study was to determine the eco-epidemiological profile and molecular characterization of SFV in a recently captured invasive population of L. chrysomelas located in Niteroi/RJ using buccal swab as an alternative collection method. A prevalence of 34.8% (32/92) and a mean viral load of 4.7 log copies of SFV/10⁶ cells were observed. With respect to time since capture, SFV prevalence was significantly higher in the group of animals sampled over 6 months after capture (55.2%) than in those more recently captured (25.4%) (p = 0.005). Infected solitary animals can contribute to SFV transmission between different groups in the population. SFV strains formed two distinct clades within the SFV infecting the Cebidae family. This is the first study to use buccal swabs as a tool to study SFV diversity and prevalence in a recently free-living NP population upon recent capture. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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21 pages, 7445 KiB

Open AccessArticle

Feline Foamy Virus Infection: Characterization of Experimental Infection and Prevalence of Natural Infection in Domestic Cats with and without Chronic Kidney Disease

by Carmen Ledesma-Feliciano, Ryan M. Troyer, Xin Zheng, Craig Miller, Rachel Cianciolo, Matteo Bordicchia, Nicholas Dannemiller, Roderick Gagne, Julia Beatty, Jessica Quimby, Martin Löchelt and Sue VandeWoude

Viruses 2019, 11(7), 662; https://doi.org/10.3390/v11070662 - 19 Jul 2019

Cited by 19 | Viewed by 6358

Abstract

Foamy viruses (FVs) are globally prevalent retroviruses that establish apparently apathogenic lifelong infections. Feline FV (FFV) has been isolated from domestic cats with concurrent diseases, including urinary syndromes. We experimentally infected five cats with FFV to study viral kinetics and tropism, peripheral blood [...] Read more.

Foamy viruses (FVs) are globally prevalent retroviruses that establish apparently apathogenic lifelong infections. Feline FV (FFV) has been isolated from domestic cats with concurrent diseases, including urinary syndromes. We experimentally infected five cats with FFV to study viral kinetics and tropism, peripheral blood mononuclear cell (PBMC) phenotype, urinary parameters, and histopathology. A persistent infection of primarily lymphoid tropism was detected with no evidence of immunological or hematologic perturbations. One cat with a significant negative correlation between lymphocytes and PBMC proviral load displayed an expanded FFV tissue tropism. Significantly increased blood urea nitrogen and ultrastructural kidney changes were noted in all experimentally infected cats, though chemistry parameters were not outside of normal ranges. Histopathological changes were observed in the brain, large intestine, and other tissues. In order to determine if there is an association of FFV with Chronic Kidney Disease, we additionally screened 125 Australian pet cats with and without CKD for FFV infection and found that FFV is highly prevalent in older cats, particularly in males with CKD, though this difference was not statistically significant compared to controls. Acute FFV infection was clinically silent, and while some measures indicated mild changes, there was no overt association of FFV infection with renal disease. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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18 pages, 5278 KiB

Open AccessArticle

The First Co-Opted Endogenous Foamy Viruses and the Evolutionary History of Reptilian Foamy Viruses

by Pakorn Aiewsakun, Peter Simmonds and Aris Katzourakis

Viruses 2019, 11(7), 641; https://doi.org/10.3390/v11070641 - 12 Jul 2019

Cited by 11 | Viewed by 4348

Abstract

A recent study reported the discovery of an endogenous reptilian foamy virus (FV), termed ERV-Spuma-Spu, found in the genome of tuatara. Here, we report two novel reptilian foamy viruses also identified as endogenous FVs (EFVs) in the genomes of panther gecko (ERV-Spuma-Ppi) and [...] Read more.

A recent study reported the discovery of an endogenous reptilian foamy virus (FV), termed ERV-Spuma-Spu, found in the genome of tuatara. Here, we report two novel reptilian foamy viruses also identified as endogenous FVs (EFVs) in the genomes of panther gecko (ERV-Spuma-Ppi) and Schlegel’s Japanese gecko (ERV-Spuma-Gja). Their presence indicates that FVs are capable of infecting reptiles in addition to mammals, amphibians, and fish. Numerous copies of full length ERV-Spuma-Spu elements were found in the tuatara genome littered with in-frame stop codons and transposable elements, suggesting that they are indeed endogenous and are not functional. ERV-Spuma-Ppi and ERV-Spuma-Gja, on the other hand, consist solely of a foamy virus-like env gene. Examination of host flanking sequences revealed that they are orthologous, and despite being more than 96 million years old, their env reading frames are fully coding competent with evidence for strong purifying selection to maintain expression and for them likely being transcriptionally active. These make them the oldest EFVs discovered thus far and the first documented EFVs that may have been co-opted for potential cellular functions. Phylogenetic analyses revealed a complex virus–host co-evolutionary history and cross-species transmission routes of ancient FVs. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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12 pages, 1393 KiB

Open AccessArticle

Isolation of an Equine Foamy Virus and Sero-Epidemiology of the Viral Infection in Horses in Japan

by Rikio Kirisawa, Yuko Toishi, Hiromitsu Hashimoto and Nobuo Tsunoda

Viruses 2019, 11(7), 613; https://doi.org/10.3390/v11070613 - 5 Jul 2019

Cited by 4 | Viewed by 2806

Abstract

An equine foamy virus (EFV) was isolated for the first time in Japan from peripheral blood mononuclear cells of a broodmare that showed wobbler syndrome after surgery for intestinal volvulus and the isolate was designated as EFVeca_LM. Complete nucleotide sequences of EFVeca_LM were [...] Read more.

An equine foamy virus (EFV) was isolated for the first time in Japan from peripheral blood mononuclear cells of a broodmare that showed wobbler syndrome after surgery for intestinal volvulus and the isolate was designated as EFVeca_LM. Complete nucleotide sequences of EFVeca_LM were determined. Nucleotide sequence analysis of the long terminal repeat (LTR) region, gag, pol, env, tas, and bel2 genes revealed that EFVeca_LM and the EFV reference strain had 97.2% to 99.1% identities. For a sero-epidemiological survey, indirect immunofluorescent antibody tests were carried out using EFVeca_LM-infected cells as an antigen against 166 sera of horses in five farms collected in 2001 to 2002 and 293 sera of horses in eight farms collected in 2014 to 2016 in Hokkaido, Japan. All of the farms had EFV antibody-positive horses, and average positive rates were 24.6% in sera obtained in 2001 to 2002 and 25.6% in sera obtained in 2014 to 2016 from broodmare farms. The positive rate in a stallion farm (Farm A) in 2002 was 10.7%, and the positive rates in two stallion farms, Farms A and B, in 2015 were 40.9% and 13.3%, respectively. The results suggested that EFV infection is maintained widely in horses in Japan. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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21 pages, 2053 KiB

Open AccessArticle

Molecular Analysis of the Complete Genome of a Simian Foamy Virus Infecting Hylobates pileatus (pileated gibbon) Reveals Ancient Co-Evolution with Lesser Apes

by Anupama Shankar, Samuel D. Sibley, Tony L. Goldberg and William M. Switzer

Viruses 2019, 11(7), 605; https://doi.org/10.3390/v11070605 - 3 Jul 2019

Cited by 2 | Viewed by 3544

Abstract

Foamy viruses (FVs) are complex retroviruses present in many mammals, including nonhuman primates, where they are called simian foamy viruses (SFVs). SFVs can zoonotically infect humans, but very few complete SFV genomes are available, hampering the design of diagnostic assays. Gibbons are lesser [...] Read more.

Foamy viruses (FVs) are complex retroviruses present in many mammals, including nonhuman primates, where they are called simian foamy viruses (SFVs). SFVs can zoonotically infect humans, but very few complete SFV genomes are available, hampering the design of diagnostic assays. Gibbons are lesser apes widespread across Southeast Asia that can be infected with SFV, but only two partial SFV sequences are currently available. We used a metagenomics approach with next-generation sequencing of nucleic acid extracted from the cell culture of a blood specimen from a lesser ape, the pileated gibbon (Hylobates pileatus), to obtain the complete SFVhpi_SAM106 genome. We used Bayesian analysis to co-infer phylogenetic relationships and divergence dates. SFVhpi_SAM106 is ancestral to other ape SFVs with a divergence date of ~20.6 million years ago, reflecting ancient co-evolution of the host and SFVhpi_SAM106. Analysis of the complete SFVhpi_SAM106 genome shows that it has the same genetic architecture as other SFVs but has the longest recorded genome (13,885-nt) due to a longer long terminal repeat region (2,071 bp). The complete sequence of the SFVhpi_SAM106 genome fills an important knowledge gap in SFV genetics and will facilitate future studies of FV infection, transmission, and evolutionary history. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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9 pages, 670 KiB

Open AccessArticle

Feline Foamy Virus is Highly Prevalent in Free-Ranging Puma concolor from Colorado, Florida and Southern California

by Sarah R. Kechejian, Nick Dannemiller, Simona Kraberger, Carmen Ledesma-Feliciano, Jennifer Malmberg, Melody Roelke Parker, Mark Cunningham, Roy McBride, Seth P. D. Riley, Winston T. Vickers, Ken Logan, Mat Alldredge, Kevin Crooks, Martin Löchelt, Scott Carver and Sue VandeWoude

Viruses 2019, 11(4), 359; https://doi.org/10.3390/v11040359 - 19 Apr 2019

Cited by 10 | Viewed by 4492

Abstract

Feline foamy virus (FFV) is a retrovirus that has been detected in multiple feline species, including domestic cats (Felis catus) and pumas (Puma concolor). FFV results in persistent infection but is generally thought to be apathogenic. Sero-prevalence in domestic [...] Read more.

Feline foamy virus (FFV) is a retrovirus that has been detected in multiple feline species, including domestic cats (Felis catus) and pumas (Puma concolor). FFV results in persistent infection but is generally thought to be apathogenic. Sero-prevalence in domestic cat populations has been documented in several countries, but the extent of viral infections in nondomestic felids has not been reported. In this study, we screened sera from 348 individual pumas from Colorado, Southern California and Florida for FFV exposure by assessing sero-reactivity using an FFV anti-Gag ELISA. We documented a sero-prevalence of 78.6% across all sampled subpopulations, representing 69.1% in Southern California, 77.3% in Colorado, and 83.5% in Florida. Age was a significant risk factor for FFV infection when analyzing the combined populations. This high prevalence in geographically distinct populations reveals widespread exposure of puma to FFV and suggests efficient shedding and transmission in wild populations. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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15 pages, 3499 KiB

Open AccessArticle

The Influence of Envelope C-Terminus Amino Acid Composition on the Ratio of Cell-Free to Cell-Cell Transmission for Bovine Foamy Virus

by Suzhen Zhang, Xiaojuan Liu, Zhibin Liang, Tiejun Bing, Wentao Qiao and Juan Tan

Viruses 2019, 11(2), 130; https://doi.org/10.3390/v11020130 - 31 Jan 2019

Cited by 24 | Viewed by 3203

Abstract

Foamy viruses (FVs) have extensive cell tropism in vitro, special replication features, and no clinical pathogenicity in naturally or experimentally infected animals, which distinguish them from orthoretroviruses. Among FVs, bovine foamy virus (BFV) has undetectable or extremely low levels of cell-free transmission in [...] Read more.

Foamy viruses (FVs) have extensive cell tropism in vitro, special replication features, and no clinical pathogenicity in naturally or experimentally infected animals, which distinguish them from orthoretroviruses. Among FVs, bovine foamy virus (BFV) has undetectable or extremely low levels of cell-free transmission in the supernatants of infected cells and mainly spreads by cell-to-cell transmission, which deters its use as a gene transfer vector. Here, using an in vitro virus evolution system, we successfully isolated high-titer cell-free BFV strains from the original cell-to-cell transmissible BFV3026 strain and further constructed an infectious cell-free BFV clone called pBS-BFV-Z1. Following sequence alignment with a cell-associated clone pBS-BFV-B, we identified a number of changes in the genome of pBS-BFV-Z1. Extensive mutagenesis analysis revealed that the C-terminus of envelope protein, especially the K898 residue, controls BFV cell-free transmission by enhancing cell-free virus entry but not the virus release capacity. Taken together, our data show the genetic determinants that regulate cell-to-cell and cell-free transmission of BFV. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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22 pages, 3248 KiB

Open AccessArticle

Clinical and Molecular Features of Feline Foamy Virus and Feline Leukemia Virus Co-Infection in Naturally-Infected Cats

by Liliane T. F. Cavalcante, Cláudia P. Muniz, Hongwei Jia, Anderson M. Augusto, Fernando Troccoli, Sheila de O. Medeiros, Carlos G. A. Dias, William M. Switzer, Marcelo A. Soares and André F. Santos

Viruses 2018, 10(12), 702; https://doi.org/10.3390/v10120702 - 11 Dec 2018

Cited by 20 | Viewed by 4819

Abstract

Feline foamy virus (FFV) and feline leukemia virus (FeLV) belong to the Retroviridae family. While disease has not been reported for FFV infection, FeLV infection can cause anemia and immunosuppression (progressive infection). Co-infection with FFV/FeLV allows evaluation of the pathogenic potential and epidemiology [...] Read more.

Feline foamy virus (FFV) and feline leukemia virus (FeLV) belong to the Retroviridae family. While disease has not been reported for FFV infection, FeLV infection can cause anemia and immunosuppression (progressive infection). Co-infection with FFV/FeLV allows evaluation of the pathogenic potential and epidemiology of FFV infection in cats with FeLV pathology. Blood and buccal swab samples from 81 cats were collected in Rio de Janeiro. Plasma was serologically tested for FeLV. DNA extracted from peripheral blood mononuclear cells and buccal swabs was used to PCR detect FFV and FeLV. A qPCR was developed to detect and measure FFV proviral loads (pVLs) in cats. FeLV qPCR was performed using previous methods. The median log10 pVL of FFV mono-infected individuals was lower than found in FFV/FeLV co-infected cats in buccal swabs (p = 0.003). We found 78% of cats had detectable buccal FFV DNA in FFV mono-infected and FFV co-infected FeLV-progressive cats, while in FeLV-regressive cats (those without signs of disease) 22% of cats had detectable buccal FFV DNA (p = 0.004). Our results suggest that regressive FeLV infection may reduce FFV saliva transmission, the main mode of FV transmission. We did not find evidence of differences in pathogenicity in FFV mono- and -dually infected cats. In summary, we show that FVs may interact with FeLV within the same host. Our study supports the utility of cats naturally co-infected with retroviruses as a model to investigate the impact of FV on immunocompromised mammalian hosts. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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Review

Jump to: Research, Other

13 pages, 435 KiB

Open AccessReview

FV Vectors as Alternative Gene Vehicles for Gene Transfer in HSCs

by Emmanouil Simantirakis, Ioannis Tsironis and George Vassilopoulos

Viruses 2020, 12(3), 332; https://doi.org/10.3390/v12030332 - 19 Mar 2020

Cited by 7 | Viewed by 3424

Abstract

Hematopoietic Stem Cells (HSCs) are a unique population of cells, capable of reconstituting the blood system of an organism through orchestrated self-renewal and differentiation. They play a pivotal role in stem cell therapies, both autologous and allogeneic. In the field of gene and [...] Read more.

Hematopoietic Stem Cells (HSCs) are a unique population of cells, capable of reconstituting the blood system of an organism through orchestrated self-renewal and differentiation. They play a pivotal role in stem cell therapies, both autologous and allogeneic. In the field of gene and cell therapy, HSCs, genetically modified or otherwise, are used to alleviate or correct a genetic defect. In this concise review, we discuss the use of SFVpsc_huHSRV.13, formerly known as Prototype Foamy Viral (PFV or FV) vectors, as vehicles for gene delivery in HSCs. We present the properties of the FV vectors that make them ideal for HSC delivery vehicles, we review their record in HSC gene marking studies and their potential as therapeutic vectors for monogenic disorders in preclinical animal models. FVs are a safe and efficient tool for delivering genes in HSCs compared to other retroviral gene delivery systems. Novel technological advancements in their production and purification in closed systems, have allowed their production under cGMP compliant conditions. It may only be a matter of time before they find their way into the clinic. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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15 pages, 487 KiB

Open AccessReview

In-Vivo Gene Therapy with Foamy Virus Vectors

by Yogendra Singh Rajawat, Olivier Humbert and Hans-Peter Kiem

Viruses 2019, 11(12), 1091; https://doi.org/10.3390/v11121091 - 23 Nov 2019

Cited by 18 | Viewed by 4517

Abstract

Foamy viruses (FVs) are nonpathogenic retroviruses that infect various animals including bovines, felines, nonhuman primates (NHPs), and can be transmitted to humans through zoonotic infection. Due to their non-pathogenic nature, broad tissue tropism and relatively safe integration profile, FVs have been engineered as [...] Read more.

Foamy viruses (FVs) are nonpathogenic retroviruses that infect various animals including bovines, felines, nonhuman primates (NHPs), and can be transmitted to humans through zoonotic infection. Due to their non-pathogenic nature, broad tissue tropism and relatively safe integration profile, FVs have been engineered as novel vectors (foamy virus vector, FVV) for stable gene transfer into different cells and tissues. FVVs have emerged as an alternative platform to contemporary viral vectors (e.g., adeno associated and lentiviral vectors) for experimental and therapeutic gene therapy of a variety of monogenetic diseases. Some of the important features of FVVs include the ability to efficiently transduce hematopoietic stem and progenitor cells (HSPCs) from humans, NHPs, canines and rodents. We have successfully used FVV for proof of concept studies to demonstrate safety and efficacy following in-vivo delivery in large animal models. In this review, we will comprehensively discuss FVV based in-vivo gene therapy approaches established in the X-linked severe combined immunodeficiency (SCID-X1) canine model. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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26 pages, 2192 KiB

Open AccessReview

Bovine Foamy Virus: Shared and Unique Molecular Features In Vitro and In Vivo

by Magdalena Materniak-Kornas, Juan Tan, Anke Heit-Mondrzyk, Agnes Hotz-Wagenblatt and Martin Löchelt

Viruses 2019, 11(12), 1084; https://doi.org/10.3390/v11121084 - 21 Nov 2019

Cited by 17 | Viewed by 3605

Abstract

The retroviral subfamily of Spumaretrovirinae consists of five genera of foamy (spuma) viruses (FVs) that are endemic in some mammalian hosts. Closely related species may be susceptible to the same or highly related FVs. FVs are not known to induce overt disease and [...] Read more.

The retroviral subfamily of Spumaretrovirinae consists of five genera of foamy (spuma) viruses (FVs) that are endemic in some mammalian hosts. Closely related species may be susceptible to the same or highly related FVs. FVs are not known to induce overt disease and thus do not pose medical problems to humans and livestock or companion animals. A robust lab animal model is not available or is a lab animal a natural host of a FV. Due to this, research is limited and often focused on the simian FVs with their well-established zoonotic potential. The authors of this review and their groups have conducted several studies on bovine FV (BFV) in the past with the intention of (i) exploring the risk of zoonotic infection via beef and raw cattle products, (ii) studying a co-factorial role of BFV in different cattle diseases with unclear etiology, (iii) exploring unique features of FV molecular biology and replication strategies in non-simian FVs, and (iv) conducting animal studies and functional virology in BFV-infected calves as a model for corresponding studies in primates or small lab animals. These studies gained new insights into FV-host interactions, mechanisms of gene expression, and transcriptional regulation, including miRNA biology, host-directed restriction of FV replication, spread and distribution in the infected animal, and at the population level. The current review attempts to summarize these findings in BFV and tries to connect them to findings from other FVs. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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15 pages, 1291 KiB

Open AccessReview

Simian Foamy Viruses in Central and South America: A New World of Discovery

by André F. Santos, Liliane T. F. Cavalcante, Cláudia P. Muniz, William M. Switzer and Marcelo A. Soares

Viruses 2019, 11(10), 967; https://doi.org/10.3390/v11100967 - 20 Oct 2019

Cited by 9 | Viewed by 3521

Abstract

Foamy viruses (FVs) are the only exogenous retrovirus to date known to infect neotropical primates (NPs). In the last decade, an increasing number of strains have been completely or partially sequenced, and molecular evolution analyses have identified an ancient co-speciation with their hosts. [...] Read more.

Foamy viruses (FVs) are the only exogenous retrovirus to date known to infect neotropical primates (NPs). In the last decade, an increasing number of strains have been completely or partially sequenced, and molecular evolution analyses have identified an ancient co-speciation with their hosts. In this review, the improvement of diagnostic techniques that allowed the determination of a more accurate prevalence of simian FVs (SFVs) in captive and free-living NPs is discussed. Determination of DNA viral load in American primates indicates that oral tissues are the viral replicative site and that buccal swab collection can be an alternative to diagnose SFV infection in NPs. Finally, the transmission potential of NP SFVs to primate workers in zoos and primate centers of the Americas is examined. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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9 pages, 198 KiB

Open AccessReview

Simian Foamy Virus Co-Infections

by Shannon M. Murray and Maxine L. Linial

Viruses 2019, 11(10), 902; https://doi.org/10.3390/v11100902 - 27 Sep 2019

Cited by 3 | Viewed by 3786

Abstract

Foamy viruses (FVs), also known as spumaretroviruses, are complex retroviruses that are seemingly nonpathogenic in natural hosts. In natural hosts, which include felines, bovines, and nonhuman primates (NHPs), a large percentage of adults are infected with FVs. For this reason, the effect of [...] Read more.

Foamy viruses (FVs), also known as spumaretroviruses, are complex retroviruses that are seemingly nonpathogenic in natural hosts. In natural hosts, which include felines, bovines, and nonhuman primates (NHPs), a large percentage of adults are infected with FVs. For this reason, the effect of FVs on infections with other viruses (co-infections) cannot be easily studied in natural populations. Most of what is known about interactions between FVs and other viruses is based on studies of NHPs in artificial settings such as research facilities. In these settings, there is some indication that FVs can exacerbate infections with lentiviruses such as simian immunodeficiency virus (SIV). Nonhuman primate (NHP) simian FVs (SFVs) have been shown to infect people without any apparent pathogenicity. Humans zoonotically infected with simian foamy virus (SFV) are often co-infected with other viruses. Thus, it is important to know whether SFV co-infections affect human disease. Full article

(This article belongs to the Special Issue Spumaretroviruses)

15 pages, 4676 KiB

Open AccessReview

Structural Insights on Retroviral DNA Integration: Learning from Foamy Viruses

by Ga-Eun Lee, Eric Mauro, Vincent Parissi, Cha-Gyun Shin and Paul Lesbats

Viruses 2019, 11(9), 770; https://doi.org/10.3390/v11090770 - 22 Aug 2019

Cited by 7 | Viewed by 4854

Abstract

Foamy viruses (FV) are retroviruses belonging to the Spumaretrovirinae subfamily. They are non-pathogenic viruses endemic in several mammalian hosts like non-human primates, felines, bovines, and equines. Retroviral DNA integration is a mandatory step and constitutes a prime target for antiretroviral therapy. This activity, [...] Read more.

Foamy viruses (FV) are retroviruses belonging to the Spumaretrovirinae subfamily. They are non-pathogenic viruses endemic in several mammalian hosts like non-human primates, felines, bovines, and equines. Retroviral DNA integration is a mandatory step and constitutes a prime target for antiretroviral therapy. This activity, conserved among retroviruses and long terminal repeat (LTR) retrotransposons, involves a viral nucleoprotein complex called intasome. In the last decade, a plethora of structural insights on retroviral DNA integration arose from the study of FV. Here, we review the biochemistry and the structural features of the FV integration apparatus and will also discuss the mechanism of action of strand transfer inhibitors. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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17 pages, 846 KiB

Open AccessReview

Structural and Functional Aspects of Foamy Virus Protease-Reverse Transcriptase

by Birgitta M. Wöhrl

Viruses 2019, 11(7), 598; https://doi.org/10.3390/v11070598 - 2 Jul 2019

Cited by 6 | Viewed by 4498

Abstract

Reverse transcription describes the process of the transformation of single-stranded RNA into double-stranded DNA via an RNA/DNA duplex intermediate, and is catalyzed by the viral enzyme reverse transcriptase (RT). This event is a pivotal step in the life cycle of all retroviruses. In [...] Read more.

Reverse transcription describes the process of the transformation of single-stranded RNA into double-stranded DNA via an RNA/DNA duplex intermediate, and is catalyzed by the viral enzyme reverse transcriptase (RT). This event is a pivotal step in the life cycle of all retroviruses. In contrast to orthoretroviruses, the domain structure of the mature RT of foamy viruses is different, i.e., it harbors the protease (PR) domain at its N-terminus, thus being a PR-RT. This structural feature has consequences on PR activation, since the enzyme is monomeric in solution and retroviral PRs are only active as dimers. This review focuses on the structural and functional aspects of simian and prototype foamy virus reverse transcription and reverse transcriptase, as well as special features of reverse transcription that deviate from orthoretroviral processes, e.g., PR activation. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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12 pages, 260 KiB

Open AccessMeeting Report

Twelfth International Foamy Virus Conference—Meeting Report

by Ottmar Herchenröder, Martin Löchelt, Florence Buseyne, Antoine Gessain, Marcelo A. Soares, Arifa S. Khan and Dirk Lindemann

Viruses 2019, 11(2), 134; https://doi.org/10.3390/v11020134 - 1 Feb 2019

Cited by 3 | Viewed by 3994

Abstract

The 12th International Foamy Virus Conference took place on 30–31 August 2018 at the Technische Universität Dresden, Dresden, Germany. The meeting included presentations on current research on non-human primate and non-primate foamy viruses (FVs; also called spumaretroviruses) as well as keynote talks on [...] Read more.

The 12th International Foamy Virus Conference took place on 30–31 August 2018 at the Technische Universität Dresden, Dresden, Germany. The meeting included presentations on current research on non-human primate and non-primate foamy viruses (FVs; also called spumaretroviruses) as well as keynote talks on related research areas in retroviruses. The taxonomy of foamy viruses was updated earlier this year to create five new genera in the subfamily, Spumaretrovirinae, based on their animal hosts. Research on viruses from different genera was presented on topics of potential relevance to human health, such as natural infections and cross-species transmission, replication, and viral-host interactions in particular with the immune system, dual retrovirus infections, virus structure and biology, and viral vectors for gene therapy. This article provides an overview of the current state-of-the-field, summarizes the meeting highlights, and presents some important questions that need to be addressed in the future. Full article

(This article belongs to the Special Issue Spumaretroviruses)

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