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14 pages, 4479 KiB

Open AccessCommunication

Mammals Preferred: Reassortment of Batai and Bunyamwera orthobunyavirus Occurs in Mammalian but Not Insect Cells

by Anna Heitmann, Frederic Gusmag, Martin G. Rathjens, Maurice Maurer, Kati Frankze, Sabine Schicht, Stephanie Jansen, Jonas Schmidt-Chanasit, Klaus Jung and Stefanie C. Becker

Viruses 2021, 13(9), 1702; https://doi.org/10.3390/v13091702 - 27 Aug 2021

Cited by 4 | Viewed by 3012

Abstract

Reassortment is a viral genome-segment recomposition known for many viruses, including the orthobunyaviruses. The co-infection of a host cell with two viruses of the same serogroup, such as the Bunyamwera orthobunyavirus and the Batai orthobunyavirus, can give rise to novel viruses. One example [...] Read more.

Reassortment is a viral genome-segment recomposition known for many viruses, including the orthobunyaviruses. The co-infection of a host cell with two viruses of the same serogroup, such as the Bunyamwera orthobunyavirus and the Batai orthobunyavirus, can give rise to novel viruses. One example is the Ngari virus, which has caused major outbreaks of human infections in Central Africa. This study aimed to investigate the potential for reassortment of Bunyamwera orthobunyavirus and the Batai orthobunyavirus during co-infection studies and the replication properties of the reassortants in different mammalian and insect cell lines. In the co-infection studies, a Ngari-like virus reassortant and a novel reassortant virus, the Batunya virus, arose in BHK-21 cells (Mesocricetus auratus). In contrast, no reassortment was observed in the examined insect cells from Aedes aegypti (Aag2) and Aedes albopictus (U4.4 and C6/36). The growth kinetic experiments show that both reassortants are replicated to higher titers in some mammalian cell lines than the parental viruses but show impaired growth in insect cell lines. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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11 pages, 1816 KiB

Open AccessArticle

Orthohantavirus Survey in Indigenous Lands in a Savannah-Like Biome, Brazil

by Ana Cláudia Pereira Terças-Trettel, Alba Valéria Gomes de Melo, Renata Carvalho de Oliveira, Alexandro Guterres, Jorlan Fernandes, Liana Stretch Pereira, Marina Atanaka, Mariano Martinez Espinosa, Bernardo Rodrigues Teixeira, Cibele Rodrigues Bonvicino, Paulo Sérgio D’Andrea and Elba Regina Sampaio de Lemos

Viruses 2021, 13(6), 1122; https://doi.org/10.3390/v13061122 - 11 Jun 2021

Cited by 2 | Viewed by 3022

Abstract

In Brazil, the first confirmed cases of hantavirus cardiopulmonary syndrome in Indigenous populations occurred in 2001. The purpose of this study was to determine the seroprevalence of orthohantavirus infections in the Utiariti Indigenous land located in the southeastern region of the Brazilian Amazon. [...] Read more.

In Brazil, the first confirmed cases of hantavirus cardiopulmonary syndrome in Indigenous populations occurred in 2001. The purpose of this study was to determine the seroprevalence of orthohantavirus infections in the Utiariti Indigenous land located in the southeastern region of the Brazilian Amazon. In December 2014 and 2015, a survey was conducted using an enzyme-linked immunosorbent assay in nine villages belonging to the Haliti–Paresí Indigenous communities. A total of 301 participants were enrolled in the study. Of the two study cohorts, the one from 2014 showed a prevalence of 12.4%, whereas the one from 2015 had a serum prevalence of 13.4%. Analysis of the paired samples of 110 Indigenous people who participated in both stages of the study enabled identification of four individuals who had seroconverted during the study period. Identifying the circulation of orthohantaviruses in the Utiariti Indigenous land highlights a serious public health problem in viral expansion and highlights the need to implement preventive measures appropriate to the sociocultural reality of these communities. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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10 pages, 1046 KiB

Open AccessArticle

Validation of Inactivation Methods for Arenaviruses

by Silke Olschewski, Anke Thielebein, Chris Hoffmann, Olivia Blake, Jonas Müller, Sabrina Bockholt, Elisa Pallasch, Julia Hinzmann, Stephanie Wurr, Neele Neddersen, Toni Rieger, Stephan Günther and Lisa Oestereich

Viruses 2021, 13(6), 968; https://doi.org/10.3390/v13060968 - 24 May 2021

Cited by 6 | Viewed by 3385

Abstract

Several of the human-pathogenic arenaviruses cause hemorrhagic fever and have to be handled under biosafety level 4 conditions, including Lassa virus. Rapid and safe inactivation of specimens containing these viruses is fundamental to enable downstream processing for diagnostics or research under lower biosafety [...] Read more.

Several of the human-pathogenic arenaviruses cause hemorrhagic fever and have to be handled under biosafety level 4 conditions, including Lassa virus. Rapid and safe inactivation of specimens containing these viruses is fundamental to enable downstream processing for diagnostics or research under lower biosafety conditions. We established a protocol to test the efficacy of inactivation methods using the low-pathogenic Morogoro arenavirus as surrogate for the related highly pathogenic viruses. As the validation of chemical inactivation methods in cell culture systems is difficult due to cell toxicity of commonly used chemicals, we employed filter devices to remove the chemical and concentrate the virus after inactivation and before inoculation into cell culture. Viral replication in the cells was monitored over 4 weeks by using indirect immunofluorescence and immunofocus assay. The performance of the protocol was verified using published inactivation methods including chemicals and heat. Ten additional methods to inactivate virus in infected cells or cell culture supernatant were validated and shown to reduce virus titers to undetectable levels. In summary, we provide a robust protocol for the validation of chemical and physical inactivation of arenaviruses in cell culture, which can be readily adapted to different inactivation methods and specimen matrices. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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14 pages, 1949 KiB

Open AccessArticle

Experimental Morogoro Virus Infection in Its Natural Host, Mastomys natalensis

by Chris Hoffmann, Stephanie Wurr, Elisa Pallasch, Sabrina Bockholt, Toni Rieger, Stephan Günther and Lisa Oestereich

Viruses 2021, 13(5), 851; https://doi.org/10.3390/v13050851 - 7 May 2021

Cited by 11 | Viewed by 2737

Abstract

Natural hosts of most arenaviruses are rodents. The human-pathogenic Lassa virus and several non-pathogenic arenaviruses such as Morogoro virus (MORV) share the same host species, namely Mastomys natalensis (M. natalensis). In this study, we investigated the history of infection and virus [...] Read more.

Natural hosts of most arenaviruses are rodents. The human-pathogenic Lassa virus and several non-pathogenic arenaviruses such as Morogoro virus (MORV) share the same host species, namely Mastomys natalensis (M. natalensis). In this study, we investigated the history of infection and virus transmission within the natural host population. To this end, we infected M. natalensis at different ages with MORV and measured the health status of the animals, virus load in blood and organs, the development of virus-specific antibodies, and the ability of the infected individuals to transmit the virus. To explore the impact of the lack of evolutionary virus–host adaptation, experiments were also conducted with Mobala virus (MOBV), which does not share M. natalensis as a natural host. Animals infected with MORV up to two weeks after birth developed persistent infection, seroconverted and were able to transmit the virus horizontally. Animals older than two weeks at the time of infection rapidly cleared the virus. In contrast, MOBV-infected neonates neither developed persistent infection nor were able to transmit the virus. In conclusion, we demonstrate that MORV is able to develop persistent infection in its natural host, but only after inoculation shortly after birth. A related arenavirus that is not evolutionarily adapted to M. natalensis is not able to establish persistent infection. Persistently infected animals appear to be important to maintain virus transmission within the host population. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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13 pages, 3574 KiB

Open AccessArticle

The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice

by Belén Borrego, Sandra Moreno, Nuria de la Losa, Friedemann Weber and Alejandro Brun

Viruses 2021, 13(4), 542; https://doi.org/10.3390/v13040542 - 24 Mar 2021

Cited by 9 | Viewed by 2211

Abstract

Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes an important disease in ruminants, with great economic losses. The infection can be also transmitted to humans; therefore, it is considered a major threat to both human and animal health. In a [...] Read more.

Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes an important disease in ruminants, with great economic losses. The infection can be also transmitted to humans; therefore, it is considered a major threat to both human and animal health. In a previous work, we described a novel RVFV variant selected in cell culture in the presence of the antiviral agent favipiravir that was highly attenuated in vivo. This variant displayed 24 amino acid substitutions in different viral proteins when compared to its parental viral strain, two of them located in the NSs protein that is known to be the major virulence factor of RVFV. By means of a reverse genetics system, in this work we have analyzed the effect that one of these substitutions, P82L, has in viral attenuation in vivo. Rescued viruses carrying this single amino acid change were clearly attenuated in BALB/c mice while their growth in an interferon (IFN)-competent cell line as well as the production of interferon beta (IFN-β) did not seem to be affected. However, the pattern of nuclear NSs accumulation was modified in cells infected with the mutant viruses. These results highlight the key role of the NSs protein in the modulation of viral infectivity. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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9 pages, 1062 KiB

Open AccessArticle

Serological and Molecular Investigation of Batai Virus Infections in Ruminants from the State of Saxony-Anhalt, Germany, 2018

by Nicole Cichon, Martin Eiden, Jana Schulz, Anne Günther, Patrick Wysocki, Cora M. Holicki, Joachim Borgwardt, Wolfgang Gaede, Martin H. Groschup and Ute Ziegler

Viruses 2021, 13(3), 370; https://doi.org/10.3390/v13030370 - 26 Feb 2021

Cited by 7 | Viewed by 2373

Abstract

Arthropod-borne Batai virus (BATV) is an Orthobunyavirus widely distributed throughout European livestock and has, in the past, been linked to febrile diseases in humans. In Germany, BATV was found in mosquitoes and in one captive harbor seal, and antibodies were recently detected in [...] Read more.

Arthropod-borne Batai virus (BATV) is an Orthobunyavirus widely distributed throughout European livestock and has, in the past, been linked to febrile diseases in humans. In Germany, BATV was found in mosquitoes and in one captive harbor seal, and antibodies were recently detected in various ruminant species. We have, therefore, conducted a follow-up study in ruminants from Saxony-Anhalt, the most affected region in Eastern Germany. A total of 325 blood samples from apparently healthy sheep, goats, and cattle were tested using a BATV-specific qRT-PCR and SNT. Even though viral RNA was not detected, the presence of antibodies was confirmed in the sera of all three species: sheep (16.5%), goats (18.3%), and cattle (41.4%). Sera were further analyzed by a glycoprotein Gc-based indirect ELISA to evaluate Gc-derived antibodies as a basis for a new serological test for BATV infections. Interestingly, the presence of neutralizing antibodies was not directly linked to the presence of BATV Gc antibodies. Overall, our results illustrate the high frequency of BATV infections in ruminants in Eastern Germany. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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20 pages, 2474 KiB

Open AccessArticle

The Atypical Kinase RIOK3 Limits RVFV Propagation and Is Regulated by Alternative Splicing

by Katherine E. Havranek, Luke Adam White, Thomas C. Bisom, Jean-Marc Lanchy and J. Stephen Lodmell

Viruses 2021, 13(3), 367; https://doi.org/10.3390/v13030367 - 26 Feb 2021

Cited by 8 | Viewed by 3349

Abstract

In recent years, transcriptome profiling studies have identified changes in host splicing patterns caused by viral invasion, yet the functional consequences of the vast majority of these splicing events remain uncharacterized. We recently showed that the host splicing landscape changes during Rift Valley [...] Read more.

In recent years, transcriptome profiling studies have identified changes in host splicing patterns caused by viral invasion, yet the functional consequences of the vast majority of these splicing events remain uncharacterized. We recently showed that the host splicing landscape changes during Rift Valley fever virus MP-12 strain (RVFV MP-12) infection of mammalian cells. Of particular interest, we observed that the host mRNA for Rio Kinase 3 (RIOK3) was alternatively spliced during infection. This kinase has been shown to be involved in pattern recognition receptor (PRR) signaling mediated by RIG-I like receptors to produce type-I interferon. Here, we characterize RIOK3 as an important component of the interferon signaling pathway during RVFV infection and demonstrate that RIOK3 mRNA expression is skewed shortly after infection to produce alternatively spliced variants that encode premature termination codons. This splicing event plays a critical role in regulation of the antiviral response. Interestingly, infection with other RNA viruses and transfection with nucleic acid-based RIG-I agonists also stimulated RIOK3 alternative splicing. Finally, we show that specifically stimulating alternative splicing of the RIOK3 transcript using a morpholino oligonucleotide reduced interferon expression. Collectively, these results indicate that RIOK3 is an important component of the mammalian interferon signaling cascade and its splicing is a potent regulatory mechanism capable of fine-tuning the host interferon response. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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11 pages, 410 KiB

Open AccessArticle

Infection, Dissemination, and Transmission Potential of North American Culex quinquefasciatus, Culex tarsalis, and Culicoides sonorensis for Oropouche Virus

by Bethany L. McGregor, C. Roxanne Connelly and Joan L. Kenney

Viruses 2021, 13(2), 226; https://doi.org/10.3390/v13020226 - 2 Feb 2021

Cited by 19 | Viewed by 4173

Abstract

Oropouche virus (OROV), a vector-borne Orthobunyavirus circulating in South and Central America, causes a febrile illness with high rates of morbidity but with no documented fatalities. Oropouche virus is transmitted by numerous vectors, including multiple genera of mosquitoes and Culicoides biting midges in [...] Read more.

Oropouche virus (OROV), a vector-borne Orthobunyavirus circulating in South and Central America, causes a febrile illness with high rates of morbidity but with no documented fatalities. Oropouche virus is transmitted by numerous vectors, including multiple genera of mosquitoes and Culicoides biting midges in South America. This study investigated the vector competence of three North American vectors, Culex tarsalis, Culex quinquefasciatus, and Culicoides sonorensis, for OROV. Cohorts of each species were fed an infectious blood meal containing 6.5 log₁₀ PFU/mL OROV and incubated for 10 or 14 days. Culex tarsalis demonstrated infection (3.13%) but not dissemination or transmission potential at 10 days post infection (DPI). At 10 and 14 DPI, Cx. quinquefasciatus demonstrated 9.71% and 19.3% infection, 2.91% and 1.23% dissemination, and 0.97% and 0.82% transmission potential, respectively. Culicoides sonorensis demonstrated 86.63% infection, 83.14% dissemination, and 19.77% transmission potential at 14 DPI. Based on these data, Cx. tarsalis is unlikely to be a competent vector for OROV. Culex quinquefasciatus demonstrated infection, dissemination, and transmission potential, although at relatively low rates. Culicoides sonorensis demonstrated high infection and dissemination but may have a salivary gland barrier to the virus. These data have implications for the spread of OROV in the event of a North American introduction. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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15 pages, 3348 KiB

Open AccessArticle

Competency of Amphibians and Reptiles and Their Potential Role as Reservoir Hosts for Rift Valley Fever Virus

by Melanie Rissmann, Nils Kley, Reiner Ulrich, Franziska Stoek, Anne Balkema-Buschmann, Martin Eiden and Martin H. Groschup

Viruses 2020, 12(11), 1206; https://doi.org/10.3390/v12111206 - 23 Oct 2020

Cited by 8 | Viewed by 2974

Abstract

Rift Valley fever phlebovirus (RVFV) is an arthropod-borne zoonotic pathogen, which is endemic in Africa, causing large epidemics, characterized by severe diseases in ruminants but also in humans. As in vitro and field investigations proposed amphibians and reptiles to potentially play a role [...] Read more.

Rift Valley fever phlebovirus (RVFV) is an arthropod-borne zoonotic pathogen, which is endemic in Africa, causing large epidemics, characterized by severe diseases in ruminants but also in humans. As in vitro and field investigations proposed amphibians and reptiles to potentially play a role in the enzootic amplification of the virus, we experimentally infected African common toads and common agamas with two RVFV strains. Lymph or sera, as well as oral, cutaneous and anal swabs were collected from the challenged animals to investigate seroconversion, viremia and virus shedding. Furthermore, groups of animals were euthanized 3, 10 and 21 days post-infection (dpi) to examine viral loads in different tissues during the infection. Our data show for the first time that toads are refractory to RVFV infection, showing neither seroconversion, viremia, shedding nor tissue manifestation. In contrast, all agamas challenged with the RVFV strain ZH501 carried virus genomes in the spleens at 3 dpi, but the animals displayed neither viremia nor virus shedding. In conclusion, the results of this study indicate that amphibians are not susceptible and reptiles are only susceptible to a low extent to RVFV, indicating that both species play, if at all, rather a subordinate role in the RVF virus ecology. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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20 pages, 2806 KiB

Open AccessArticle

A Model for the Production of Regulatory Grade Viral Hemorrhagic Fever Exposure Stocks: From Field Surveillance to Advanced Characterization of SFTSV

by Unai Perez-Sautu, Se Hun Gu, Katie Caviness, Dong Hyun Song, Yu-Jin Kim, Nicholas Di Paola, Daesang Lee, Terry A. Klein, Joseph A. Chitty, Elyse Nagle, Heung-Chul Kim, Sung-Tae Chong, Brett Beitzel, Daniel S. Reyes, Courtney Finch, Russ Byrum, Kurt Cooper, Janie Liang, Jens H. Kuhn, Xiankun Zeng, Kathleen A. Kuehl, Kayla M. Coffin, Jun Liu, Hong Sang Oh, Woong Seog, Byung-Sub Choi, Mariano Sanchez-Lockhart, Gustavo Palacios and Seong Tae Jeong Show full author list Hide full author list

Viruses 2020, 12(9), 958; https://doi.org/10.3390/v12090958 - 29 Aug 2020

Cited by 6 | Viewed by 4225

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging human pathogen, endemic in areas of China, Japan, and the Korea (KOR). It is primarily transmitted through infected ticks and can cause a severe hemorrhagic fever disease with case fatality rates as high [...] Read more.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging human pathogen, endemic in areas of China, Japan, and the Korea (KOR). It is primarily transmitted through infected ticks and can cause a severe hemorrhagic fever disease with case fatality rates as high as 30%. Despite its high virulence and increasing prevalence, molecular and functional studies in situ are scarce due to the limited availability of high-titer SFTSV exposure stocks. During the course of field virologic surveillance in 2017, we detected SFTSV in ticks and in a symptomatic soldier in a KOR Army training area. SFTSV was isolated from the ticks producing a high-titer viral exposure stock. Through the use of advanced genomic tools, we present here a complete, in-depth characterization of this viral stock, including a comparison with both the virus in its arthropod source and in the human case, and an in vivo study of its pathogenicity. Thanks to this detailed characterization, this SFTSV viral exposure stock constitutes a quality biological tool for the study of this viral agent and for the development of medical countermeasures, fulfilling the requirements of the main regulatory agencies. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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Review

Jump to: Research

35 pages, 2012 KiB

Open AccessReview

The Bunyavirales: The Plant-Infecting Counterparts

by Richard Kormelink, Jeanmarie Verchot, Xiaorong Tao and Cecile Desbiez

Viruses 2021, 13(5), 842; https://doi.org/10.3390/v13050842 - 6 May 2021

Cited by 33 | Viewed by 5845

Abstract

Negative-strand (-) RNA viruses (NSVs) comprise a large and diverse group of viruses that are generally divided in those with non-segmented and those with segmented genomes. Whereas most NSVs infect animals and humans, the smaller group of the plant-infecting counterparts is expanding, with [...] Read more.

Negative-strand (-) RNA viruses (NSVs) comprise a large and diverse group of viruses that are generally divided in those with non-segmented and those with segmented genomes. Whereas most NSVs infect animals and humans, the smaller group of the plant-infecting counterparts is expanding, with many causing devastating diseases worldwide, affecting a large number of major bulk and high-value food crops. In 2018, the taxonomy of segmented NSVs faced a major reorganization with the establishment of the order Bunyavirales. This article overviews the major plant viruses that are part of the order, i.e., orthospoviruses (Tospoviridae), tenuiviruses (Phenuiviridae), and emaraviruses (Fimoviridae), and provides updates on the more recent ongoing research. Features shared with the animal-infecting counterparts are mentioned, however, special attention is given to their adaptation to plant hosts and vector transmission, including intra/intercellular trafficking and viral counter defense to antiviral RNAi. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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29 pages, 2341 KiB

Open AccessReview

Host Cell Restriction Factors of Bunyaviruses and Viral Countermeasures

by Solène Lerolle, Natalia Freitas, François-Loïc Cosset and Vincent Legros

Viruses 2021, 13(5), 784; https://doi.org/10.3390/v13050784 - 28 Apr 2021

Cited by 12 | Viewed by 5147

Abstract

The Bunyavirales order comprises more than 500 viruses (generally defined as bunyaviruses) classified into 12 families. Some of these are highly pathogenic viruses infecting different hosts, including humans, mammals, reptiles, arthropods, birds, and/or plants. Host cell sensing of infection activates the innate immune [...] Read more.

The Bunyavirales order comprises more than 500 viruses (generally defined as bunyaviruses) classified into 12 families. Some of these are highly pathogenic viruses infecting different hosts, including humans, mammals, reptiles, arthropods, birds, and/or plants. Host cell sensing of infection activates the innate immune system that aims at inhibiting viral replication and propagation. Upon recognition of pathogen-associated molecular patterns (PAMPs) by cellular pattern recognition receptors (PRRs), numerous signaling cascades are activated, leading to the production of interferons (IFNs). IFNs act in an autocrine and paracrine manner to establish an antiviral state by inducing the expression of hundreds of IFN-stimulated genes (ISGs). Some of these ISGs are known to restrict bunyavirus infection. Along with other constitutively expressed host cellular factors with antiviral activity, these proteins (hereafter referred to as “restriction factors”) target different steps of the viral cycle, including viral entry, genome transcription and replication, and virion egress. In reaction to this, bunyaviruses have developed strategies to circumvent this antiviral response, by avoiding cellular recognition of PAMPs, inhibiting IFN production or interfering with the IFN-mediated response. Herein, we review the current knowledge on host cellular factors that were shown to restrict infections by bunyaviruses. Moreover, we focus on the strategies developed by bunyaviruses in order to escape the antiviral state developed by the infected cells. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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27 pages, 4939 KiB

Open AccessReview

Insights into the Pathogenesis of Viral Haemorrhagic Fever Based on Virus Tropism and Tissue Lesions of Natural Rift Valley Fever

by Lieza Odendaal, A Sally Davis and Estelle H Venter

Viruses 2021, 13(4), 709; https://doi.org/10.3390/v13040709 - 20 Apr 2021

Cited by 20 | Viewed by 4655

Abstract

Rift Valley fever phlebovirus (RVFV) infects humans and a wide range of ungulates and historically has caused devastating epidemics in Africa and the Arabian Peninsula. Lesions of naturally infected cases of Rift Valley fever (RVF) have only been described in detail in sheep [...] Read more.

Rift Valley fever phlebovirus (RVFV) infects humans and a wide range of ungulates and historically has caused devastating epidemics in Africa and the Arabian Peninsula. Lesions of naturally infected cases of Rift Valley fever (RVF) have only been described in detail in sheep with a few reports concerning cattle and humans. The most frequently observed lesion in both ruminants and humans is randomly distributed necrosis, particularly in the liver. Lesions supportive of vascular endothelial injury are also present and include mild hydropericardium, hydrothorax and ascites; marked pulmonary congestion and oedema; lymph node congestion and oedema; and haemorrhages in many tissues. Although a complete understanding of RVF pathogenesis is still lacking, antigen-presenting cells in the skin are likely the early targets of the virus. Following suppression of type I IFN production and necrosis of dermal cells, RVFV spreads systemically, resulting in infection and necrosis of other cells in a variety of organs. Failure of both the innate and adaptive immune responses to control infection is exacerbated by apoptosis of lymphocytes. An excessive pro-inflammatory cytokine and chemokine response leads to microcirculatory dysfunction. Additionally, impairment of the coagulation system results in widespread haemorrhages. Fatal outcomes result from multiorgan failure, oedema in many organs (including the lungs and brain), hypotension, and circulatory shock. Here, we summarize current understanding of RVF cellular tropism as informed by lesions caused by natural infections. We specifically examine how extant knowledge informs current understanding regarding pathogenesis of the haemorrhagic fever form of RVF, identifying opportunities for future research. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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30 pages, 4963 KiB

Open AccessReview

Recent Advances in Bunyavirus Glycoprotein Research: Precursor Processing, Receptor Binding and Structure

by Ruben J. G. Hulswit, Guido C. Paesen, Thomas A. Bowden and Xiaohong Shi

Viruses 2021, 13(2), 353; https://doi.org/10.3390/v13020353 - 23 Feb 2021

Cited by 41 | Viewed by 6229

Abstract

The Bunyavirales order accommodates related viruses (bunyaviruses) with segmented, linear, single-stranded, negative- or ambi-sense RNA genomes. Their glycoproteins form capsomeric projections or spikes on the virion surface and play a crucial role in virus entry, assembly, morphogenesis. Bunyavirus glycoproteins are encoded by a [...] Read more.

The Bunyavirales order accommodates related viruses (bunyaviruses) with segmented, linear, single-stranded, negative- or ambi-sense RNA genomes. Their glycoproteins form capsomeric projections or spikes on the virion surface and play a crucial role in virus entry, assembly, morphogenesis. Bunyavirus glycoproteins are encoded by a single RNA segment as a polyprotein precursor that is co- and post-translationally cleaved by host cell enzymes to yield two mature glycoproteins, Gn and Gc (or GP1 and GP2 in arenaviruses). These glycoproteins undergo extensive N-linked glycosylation and despite their cleavage, remain associated to the virion to form an integral transmembrane glycoprotein complex. This review summarizes recent advances in our understanding of the molecular biology of bunyavirus glycoproteins, including their processing, structure, and known interactions with host factors that facilitate cell entry. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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21 pages, 1271 KiB

Open AccessReview

A Look into Bunyavirales Genomes: Functions of Non-Structural (NS) Proteins

by Shanna S. Leventhal, Drew Wilson, Heinz Feldmann and David W. Hawman

Viruses 2021, 13(2), 314; https://doi.org/10.3390/v13020314 - 18 Feb 2021

Cited by 40 | Viewed by 6956

Abstract

In 2016, the Bunyavirales order was established by the International Committee on Taxonomy of Viruses (ICTV) to incorporate the increasing number of related viruses across 13 viral families. While diverse, four of the families (Peribunyaviridae, Nairoviridae, Hantaviridae, and Phenuiviridae) contain known [...] Read more.

In 2016, the Bunyavirales order was established by the International Committee on Taxonomy of Viruses (ICTV) to incorporate the increasing number of related viruses across 13 viral families. While diverse, four of the families (Peribunyaviridae, Nairoviridae, Hantaviridae, and Phenuiviridae) contain known human pathogens and share a similar tri-segmented, negative-sense RNA genomic organization. In addition to the nucleoprotein and envelope glycoproteins encoded by the small and medium segments, respectively, many of the viruses in these families also encode for non-structural (NS) NSs and NSm proteins. The NSs of Phenuiviridae is the most extensively studied as a host interferon antagonist, functioning through a variety of mechanisms seen throughout the other three families. In addition, functions impacting cellular apoptosis, chromatin organization, and transcriptional activities, to name a few, are possessed by NSs across the families. Peribunyaviridae, Nairoviridae, and Phenuiviridae also encode an NSm, although less extensively studied than NSs, that has roles in antagonizing immune responses, promoting viral assembly and infectivity, and even maintenance of infection in host mosquito vectors. Overall, the similar and divergent roles of NS proteins of these human pathogenic Bunyavirales are of particular interest in understanding disease progression, viral pathogenesis, and developing strategies for interventions and treatments. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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16 pages, 1253 KiB

Open AccessReview

Entry of Phenuiviruses into Mammalian Host Cells

by Jana Koch, Qilin Xin, Nicole D. Tischler and Pierre-Yves Lozach

Viruses 2021, 13(2), 299; https://doi.org/10.3390/v13020299 - 14 Feb 2021

Cited by 25 | Viewed by 4274

Abstract

Phenuiviridae is a large family of arthropod-borne viruses with over 100 species worldwide. Several cause severe diseases in both humans and livestock. Global warming and the apparent geographical expansion of arthropod vectors are good reasons to seriously consider these viruses potential agents of [...] Read more.

Phenuiviridae is a large family of arthropod-borne viruses with over 100 species worldwide. Several cause severe diseases in both humans and livestock. Global warming and the apparent geographical expansion of arthropod vectors are good reasons to seriously consider these viruses potential agents of emerging diseases. With an increasing frequency and number of epidemics, some phenuiviruses represent a global threat to public and veterinary health. This review focuses on the early stage of phenuivirus infection in mammalian host cells. We address current knowledge on each step of the cell entry process, from virus binding to penetration into the cytosol. Virus receptors, endocytosis, and fusion mechanisms are discussed in light of the most recent progress on the entry of banda-, phlebo-, and uukuviruses, which together constitute the three prominent genera in the Phenuiviridae family. Full article

(This article belongs to the Special Issue Bunyavirus 2020)

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