-
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 -
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 -
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 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 -
Cell Reports Mar 2023La Crosse virus, responsible for pediatric encephalitis in the United States, and Schmallenberg virus, a highly teratogenic veterinary virus in Europe, belong to the...
La Crosse virus, responsible for pediatric encephalitis in the United States, and Schmallenberg virus, a highly teratogenic veterinary virus in Europe, belong to the large Orthobunyavirus genus of zoonotic arthropod-borne pathogens distributed worldwide. Viruses in this under-studied genus cause CNS infections or fever with debilitating arthralgia/myalgia syndromes, with no effective treatment. The main surface antigen, glycoprotein Gc (∼1,000 residues), has a variable N-terminal half (Gc) targeted by the patients' antibody response and a conserved C-terminal moiety (Gc) responsible for membrane fusion during cell entry. Here, we report the X-ray structure of post-fusion La Crosse and Schmallenberg virus Gc, revealing the molecular determinants for hairpin formation and trimerization required to drive membrane fusion. We further experimentally confirm the role of residues in the fusion loops and in a vestigial endoplasmic reticulum (ER) translocation sequence at the Gc-Gc junction. The resulting knowledge provides essential molecular underpinnings for future development of potential therapeutic treatments and vaccines.
Topics: Humans; Child; Orthobunyavirus; Membrane Glycoproteins; Membrane Fusion; Glycoproteins; La Crosse virus
PubMed: 36827185
DOI: 10.1016/j.celrep.2023.112142 -
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 -
Viruses Aug 2022Batai virus (BATV) is a zoonotic orthobunyavirus transmitted by a wide range of mosquito vectors. The virus is distributed throughout Asia and parts of Africa and has... (Review)
Review
Batai virus (BATV) is a zoonotic orthobunyavirus transmitted by a wide range of mosquito vectors. The virus is distributed throughout Asia and parts of Africa and has been sporadically detected in several European countries. There is increasing evidence that BATV is emerging in Europe as a potential threat to both animal and human health, having been detected in mosquitoes, mammals, birds and humans. In recent years, serological surveillance in cattle, sheep and goats has suggested an antibody prevalence of up to 46% in European livestock, although human serological prevalence remains generally low. However, the recent and continued spread of invasive mosquito species into Europe may facilitate the establishment of competent populations of mosquitoes leading to increased BATV transmission. Migratory birds may also potentially facilitate the emergence of BATV in geographical locations where it was previously undetected. Although BATV has the potential to cause disease in humans and livestock, our understanding of the impact in wild animal populations is extremely limited. Therefore, there is a need for increased surveillance for BATV in mosquitoes, livestock, wild mammals and birds in Europe to understand the true impact of this virus.
Topics: Animals; Bunyamwera virus; Cattle; Culicidae; Europe; Goats; Humans; Orthobunyavirus; Phylogeny; Sheep
PubMed: 36146674
DOI: 10.3390/v14091868 -
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 -
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 -
Revue Scientifique Et Technique... Aug 2015Akabane virus is a Culicoides-borne orthobunyavirus that is teratogenic to the fetus of cattle and small ruminant species. Depending upon the stage of gestation atwhich...
Akabane virus is a Culicoides-borne orthobunyavirus that is teratogenic to the fetus of cattle and small ruminant species. Depending upon the stage of gestation atwhich infection occurs, and the length of gestation of the mammalian host, a range of congenital defects may be observed. The developing central nervous system is usually the most severely affected, with hydranencephaly and arthrogryposis most frequently observed. Less commonly, some strains of Akabane virus can cause encephalitis in the neonate or, rarely, adult cattle. Akabane viruses are known to be widespread in temperate and tropical regions of Australia, Southeast Asia, the Middle East and some African countries. Disease is infrequently observed in regions where this virus is endemic and the presence of the virus remains unrecognised in the absence of serological surveillance. In some Asian countries, vaccines are used to minimise the occurrence of disease.
Topics: Animals; Bunyaviridae Infections; Orthobunyavirus
PubMed: 26601444
DOI: 10.20506/rst.34.2.2366