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The New England Journal of Medicine Apr 2011Heightened surveillance of acute febrile illness in China since 2009 has led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with an...
BACKGROUND
Heightened surveillance of acute febrile illness in China since 2009 has led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with an unknown cause. Infection with Anaplasma phagocytophilum has been suggested as a cause, but the pathogen has not been detected in most patients on laboratory testing.
METHODS
We obtained blood samples from patients with the case definition of SFTS in six provinces in China. The blood samples were used to isolate the causal pathogen by inoculation of cell culture and for detection of viral RNA on polymerase-chain-reaction assay. The pathogen was characterized on electron microscopy and nucleic acid sequencing. We used enzyme-linked immunosorbent assay, indirect immunofluorescence assay, and neutralization testing to analyze the level of virus-specific antibody in patients' serum samples.
RESULTS
We isolated a novel virus, designated SFTS bunyavirus, from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction. RNA sequence analysis revealed that the virus was a newly identified member of the genus phlebovirus in the Bunyaviridae family. Electron-microscopical examination revealed virions with the morphologic characteristics of a bunyavirus. The presence of the virus was confirmed in 171 patients with SFTS from six provinces by detection of viral RNA, specific antibodies to the virus in blood, or both. Serologic assays showed a virus-specific immune response in all 35 pairs of serum samples collected from patients during the acute and convalescent phases of the illness.
CONCLUSIONS
A novel phlebovirus was identified in patients with a life-threatening illness associated with fever and thrombocytopenia in China. (Funded by the China Mega-Project for Infectious Diseases and others.).
Topics: Adult; Aged; Aged, 80 and over; Animals; Antibodies, Viral; Bunyaviridae Infections; China; Communicable Diseases, Emerging; Female; Fever; Genome, Viral; Humans; Ixodidae; Male; Microscopy, Electron, Transmission; Middle Aged; Orthobunyavirus; Phylogeny; RNA, Viral; Reverse Transcriptase Polymerase Chain Reaction; Thrombocytopenia
PubMed: 21410387
DOI: 10.1056/NEJMoa1010095 -
Autophagy Jul 2022Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging negatively stranded enveloped RNA bunyavirus that causes SFTS with a high case fatality rate of...
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging negatively stranded enveloped RNA bunyavirus that causes SFTS with a high case fatality rate of up to 30%. Macroautophagy/autophagy is an evolutionarily conserved process involved in the maintenance of host homeostasis, which exhibits anti-viral or pro-viral responses in reaction to different viral challenges. However, the interaction between the bunyavirus SFTSV and the autophagic process is still largely unclear. By establishing various autophagy-deficient cell lines, we found that SFTSV triggered RB1CC1/FIP200-BECN1-ATG5-dependent classical autophagy flux. SFTSV nucleoprotein induced BECN1-dependent autophagy by disrupting the BECN1-BCL2 association. Importantly, SFTSV utilized autophagy for the viral life cycle, which not only assembled in autophagosomes derived from the ERGIC and Golgi complex, but also utilized autophagic vesicles for exocytosis. Taken together, our results suggest a novel virus-autophagy interaction model in which bunyavirus SFTSV induces classical autophagy flux for viral assembly and egress processes, suggesting that autophagy inhibition may be a novel therapy for treating or releasing SFTS.
Topics: Autophagy; Humans; Orthobunyavirus; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Virus Assembly
PubMed: 34747299
DOI: 10.1080/15548627.2021.1994296 -
Viruses Nov 2014The Bunyaviridae family is comprised of more than 350 viruses, of which many within the Hantavirus, Orthobunyavirus, Nairovirus, Tospovirus, and Phlebovirus genera are... (Review)
Review
The Bunyaviridae family is comprised of more than 350 viruses, of which many within the Hantavirus, Orthobunyavirus, Nairovirus, Tospovirus, and Phlebovirus genera are significant human or agricultural pathogens. The viruses within the Orthobunyavirus, Nairovirus, and Phlebovirus genera are transmitted by hematophagous arthropods, such as mosquitoes, midges, flies, and ticks, and their associated arthropods not only serve as vectors but also as virus reservoirs in many cases. This review presents an overview of several important emerging or re-emerging bunyaviruses and describes what is known about bunyavirus-vector interactions based on epidemiological, ultrastructural, and genetic studies of members of this virus family.
Topics: Animals; Arthropod Vectors; Arthropods; Bunyaviridae Infections; Host-Pathogen Interactions; Humans; Orthobunyavirus
PubMed: 25402172
DOI: 10.3390/v6114373 -
Viruses May 2022Dozens of orthobunyaviruses have been isolated in Brazil, and at least thirteen have been associated with human disease. The Oropouche virus has received most attention... (Review)
Review
Dozens of orthobunyaviruses have been isolated in Brazil, and at least thirteen have been associated with human disease. The Oropouche virus has received most attention for having caused explosive epidemics with hundreds of thousands of cases in the north region between the 1960sand the 1980s, and since then has been sporadically detected elsewhere in the country. Despite their importance, little is known about their enzootic cycles of transmission, amplifying hosts and vectors, and biotic and abiotic factors involved in spillover events to humans. This overview aims to combine available data of neglected orthobunyaviruses of several serogroups, namely, Anopheles A, Anopheles B, Bunyamwera, California, Capim, Gamboa, Group C, Guama, Simbu and Turlock, in order to evaluate the current knowledge and identify research gaps in their natural transmission cycles in Brazil to ultimately point to the future direction in which orthobunyavirus research should be guided.
Topics: Animals; Anopheles; Brazil; Humans; Mosquito Vectors; Orthobunyavirus; Serogroup
PubMed: 35632729
DOI: 10.3390/v14050987 -
Viruses Sep 2022Bunyaviruses represent the largest group of RNA viruses and are the causative agent of a variety of febrile and hemorrhagic illnesses. Originally characterized as a... (Review)
Review
Bunyaviruses represent the largest group of RNA viruses and are the causative agent of a variety of febrile and hemorrhagic illnesses. Originally characterized as a single serotype in Africa, the number of described bunyaviruses now exceeds over 500, with its presence detected around the world. These predominantly tri-segmented, single-stranded RNA viruses are transmitted primarily through arthropod and rodent vectors and can infect a wide variety of animals and plants. Although encoding for a small number of proteins, these viruses can inflict potentially fatal disease outcomes and have even developed strategies to suppress the innate antiviral immune mechanisms of the infected host. This short review will attempt to provide an overall description of the order , describing the mechanisms behind their infection, replication, and their evasion of the host immune response. Furthermore, the historical context of these viruses will be presented, starting from their original discovery almost 80 years ago to the most recent research pertaining to viral replication and host immune response.
Topics: Animals; Bunyaviridae; Orthobunyavirus; Virus Replication; RNA Viruses; Antiviral Agents
PubMed: 36298693
DOI: 10.3390/v14102139 -
Current Opinion in Virology Dec 2022The Bunyavirales order is the largest grouping of RNA viruses, comprising emerging and re-emerging human, plant and animal pathogens. Bunyaviruses have a global... (Review)
Review
The Bunyavirales order is the largest grouping of RNA viruses, comprising emerging and re-emerging human, plant and animal pathogens. Bunyaviruses have a global distribution and many members of the order are transmitted by arthropods. They have evolved a plethora of mechanisms to manipulate the regulatory processes of the infected cell to facilitate their own replicative cycle, in hosts of disparate phylogenies. Interest in virus-vector interactions is growing rapidly. However, current understanding of tick-borne bunyavirus cellular interaction is heavily biased to studies conducted in mammalian systems. In this short review, we summarise current understandings of how tick-borne bunyaviruses utilise major cellular pathways (innate immunity, apoptosis and RNAi responses) in mammalian or tick cells to facilitate virus replication.
Topics: Animals; Humans; Orthobunyavirus; Host Microbial Interactions; Bunyaviridae; Tick-Borne Diseases; Ticks; Bunyaviridae Infections; Mammals
PubMed: 36375406
DOI: 10.1016/j.coviro.2022.101278 -
PLoS Pathogens Jan 2023Bunyaviruses are negative sense, single-strand RNA viruses that infect a wide range of vertebrate, invertebrate and plant hosts. WHO lists three bunyavirus diseases as... (Review)
Review
Bunyaviruses are negative sense, single-strand RNA viruses that infect a wide range of vertebrate, invertebrate and plant hosts. WHO lists three bunyavirus diseases as priority diseases requiring urgent development of medical countermeasures highlighting their high epidemic potential. While the viral large (L) protein containing the RNA-dependent RNA polymerase is a key enzyme in the viral replication cycle and therefore a suitable drug target, our knowledge on the structure and activities of this multifunctional protein has, until recently, been very limited. However, in the last few years, facilitated by the technical advances in the field of cryogenic electron microscopy, many structures of bunyavirus L proteins have been solved. These structures significantly enhance our mechanistic understanding of bunyavirus genome replication and transcription processes and highlight differences and commonalities between the L proteins of different bunyavirus families. Here, we provide a review of our current understanding of genome replication and transcription in bunyaviruses with a focus on the viral L protein. Further, we compare within bunyaviruses and with the related influenza virus polymerase complex and highlight open questions.
Topics: Bunyaviridae; Orthobunyavirus; RNA; Viral Proteins; Virus Replication
PubMed: 36634042
DOI: 10.1371/journal.ppat.1011060 -
PLoS Neglected Tropical Diseases Oct 2020The Orthobunyavirus genus comprises a wide range of arthropod-borne viruses which are prevalent worldwide and commonly associated with central nervous system (CNS)... (Review)
Review
The Orthobunyavirus genus comprises a wide range of arthropod-borne viruses which are prevalent worldwide and commonly associated with central nervous system (CNS) disease in humans and other vertebrates. Several orthobunyaviruses have recently emerged and increasingly more will likely do so in the future. Despite this large number, an overview of these viruses is currently lacking, making it challenging to determine importance from a One Health perspective. Causality is a key feature of determining importance, yet classical tools are unfit to evaluate the causality of orthobunyaviral CNS disease. Therefore, we aimed to provide an overview of orthobunyaviral CNS disease in vertebrates and objectify the causality strength of each virus. In total, we identified 27 orthobunyaviruses described in literature to be associated with CNS disease. Ten were associated with disease in multiple host species of which seven included humans. Seven viruses were associated with both congenital and postnatal CNS disease. CNS disease-associated orthobunyaviruses were spread across all known Orthobunyavirus serogroups by phylogenetic analyses. Taken together, these results indicate that orthobunyaviruses may have a common tendency to infect the CNS of vertebrates. Next, we developed six tailor-made causality indicators and evaluated the causality strength of each of the identified orthobunyaviruses. Nine viruses had a 'strong' causality score and were deemed causal. Eight had a 'moderate' and ten a 'weak' causality score. Notably, there was a lack of case-control studies, which was only available for one virus. We, therefore, stress the importance of proper case-control studies as a fundamental aspect of proving causality. This comprehensible overview can be used to identify orthobunyaviruses which may be considered causal, reveal research gaps for viruses with moderate to low causality scores, and provide a framework to evaluate the causality of orthobunyaviruses that may newly emerge in the future.
Topics: Animals; Bunyaviridae Infections; Central Nervous System Diseases; Communicable Diseases, Emerging; Humans; Orthobunyavirus
PubMed: 33112863
DOI: 10.1371/journal.pntd.0008856 -
Virus Genes Apr 2020The viruses historically implicated or currently considered as candidates for misuse in bioterrorist events are poxviruses, filoviruses, bunyaviruses, orthomyxoviruses,... (Review)
Review
The viruses historically implicated or currently considered as candidates for misuse in bioterrorist events are poxviruses, filoviruses, bunyaviruses, orthomyxoviruses, paramyxoviruses and a number of arboviruses causing encephalitis, including alpha- and flaviviruses. All these viruses are of concern for public health services when they occur in natural outbreaks or emerge in unvaccinated populations. Recent events and intelligence reports point to a growing risk of dangerous biological agents being used for nefarious purposes. Public health responses effective in natural outbreaks of infectious disease may not be sufficient to deal with the severe consequences of a deliberate release of such agents. One important aspect of countermeasures against viral biothreat agents are the antiviral treatment options available for use in post-exposure prophylaxis. These issues were adressed by the organizers of the 16th Medical Biodefense Conference, held in Munich in 2018, in a special session on the development of drugs to treat infections with viruses currently perceived as a threat to societies or associated with a potential for misuse as biothreat agents. This review will outline the state-of-the-art methods in antivirals research discussed and provide an overview of antiviral compounds in the pipeline that are already approved for use or still under development.
Topics: Antiviral Agents; Arboviruses; Bioterrorism; Filoviridae; Humans; Orthobunyavirus; Orthomyxoviridae; Paramyxovirinae; Poxviridae; Virus Diseases
PubMed: 32076918
DOI: 10.1007/s11262-020-01737-5 -
Trends in Microbiology Apr 2020In common with all segmented negative-sense RNA viruses, bunyavirus transcripts contain heterologous sequences at their 5' termini originating from capped host cell... (Review)
Review
In common with all segmented negative-sense RNA viruses, bunyavirus transcripts contain heterologous sequences at their 5' termini originating from capped host cell RNAs. These heterologous sequences are acquired by a so-called cap-snatching mechanism. Whereas for nuclear replicating influenza virus the source of capped primers as well as the cap-binding and endonuclease activities of the viral polymerase needed for cap snatching have been functionally and structurally well characterized, our knowledge on the expected counterparts of cytoplasmic replicating bunyaviruses is still limited and controversial. This review focuses on the cap-snatching mechanism of bunyaviruses in the light of recent structural and functional data.
Topics: Endonucleases; Orthobunyavirus; Orthomyxoviridae; RNA Caps; RNA, Viral; Transcription, Genetic; Viral Proteins; Virus Replication
PubMed: 31948728
DOI: 10.1016/j.tim.2019.12.006