Characterization of the Bhanja Serogroup Viruses (Bunyaviridae): a Novel Species of the Genus Phlebovirus and Its Relationship with Other Emerging Tick-Borne Phleboviruses

Matsuno, Keita; Weisend, Carla; Rosa, A.P.A. Travassos da; Anzick, Sarah L.; Dahlstrom, Eric; Porcella, Stephen F.; Dorward, David W.; Yu, Xue‐Jie; Tesh, Robert B.; Ebihara, Hideki

doi:10.1128/jvi.02845-12

Cited by 100 publications

(79 citation statements)

References 37 publications

(40 reference statements)

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“…SFTSV is most closely related to the Heartland virus, recently isolated from patients in the USA, with nearly 70% RNA sequence homology. SFTSV is next closely related to the Uukuniemi virus and Bhanja virus [3,8,9].…”

Section: Sftsv and Its Molecular Biologymentioning

confidence: 99%

An emerging hemorrhagic fever in China caused by a novel bunyavirus SFTSV

Zhang

Liu

Zhao

et al. 2013

Sci. China Life Sci.

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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in rural areas of China and is caused by a new bunyavirus, SFTSV, named after the disease. The transmission vectors and animal hosts of SFTSV are unclear. Ticks are the most likely transmission vectors and domestic animals, including goats, dogs, and cattle, are potential amplifying hosts of SFTSV. The clinical symptoms of SFTS are nonspecific, but major symptoms include fever, gastrointestinal symptoms, myalgia, dizziness, joint pain, chills, and regional lymphadenopathy. The most common abnormalities in laboratory test results are thrombocytopenia (95%), leukocytopenia (86%), and elevated levels of serum alanine aminotransferase, aspartate aminotransferase, creatine kinase, and lactate dehydrogenase. The fatality rate for SFTS is 12% on average, and the annual incidence of the disease is approximately five per 100000 of the rural population.

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Section: Sftsv and Its Molecular Biologymentioning

confidence: 99%

An emerging hemorrhagic fever in China caused by a novel bunyavirus SFTSV

Zhang

Liu

Zhao

et al. 2013

Sci. China Life Sci.

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“…A few cases of febrile illness in humans have been described, and serological surveys in Eastern Europe suggest that BHAV is endemic in that region and may cause undetected human infection (6,25). Two recent papers report nucleotide sequence determination of Bhanja group viruses (26,27) and show that they are related to SFTSV and HRTV. Lone Star virus (LSV) was originally isolated from A. americanum (the lone star tick) in Kentucky in 1967 (28) and, like BHAV, was an unclassified member of the Bunyaviridae.…”

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confidence: 99%

Reverse Genetics System for Severe Fever with Thrombocytopenia Syndrome Virus

Brennan

Zhang

et al. 2015

J Virol

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Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen that was first reported in China in 2009. Phylogenetic analysis of the viral genome showed that SFTS virus represents a new lineage within the Phlebovirus genus, distinct from the existing sandfly fever and Uukuniemi virus groups, in the family Bunyaviridae. SFTS disease is characterized by gastrointestinal symptoms, chills, joint pain, myalgia, thrombocytopenia, leukocytopenia, and some hemorrhagic manifestations with a case fatality rate of about 2 to 15%. Here we report the development of reverse genetics systems to study STFSV replication and pathogenesis. We developed and optimized functional T7 polymerase-based M-and S-segment minigenome assays, which revealed errors in the published terminal sequences of the S segment of the Hubei 29 strain of SFTSV. We then generated recombinant viruses from cloned cDNAs prepared to the antigenomic RNAs both of the minimally passaged virus (HB29) and of a cell culture-adapted strain designated HB29pp. The growth properties, pattern of viral protein synthesis, and subcellular localization of viral N and NSs proteins of wild-type HB29pp (wtHB29pp) and recombinant HB29pp viruses were indistinguishable. We also show that the viruses fail to shut off host cell polypeptide production. The robust reverse genetics system described will be a valuable tool for the design of therapeutics and the development of killed and attenuated vaccines against this important emerging pathogen. IMPORTANCESFTSV and related tick-borne phleboviruses such as Heartland virus are emerging viruses shown to cause severe disease in humans in the Far East and the United States, respectively. Study of these novel pathogens would be facilitated by technology to manipulate these viruses in a laboratory setting using reverse genetics. Here, we report the generation of infectious SFTSV from cDNA clones and demonstrate that the behavior of recombinant viruses is similar to that of the wild type. This advance will allow for further dissection of the roles of each of the viral proteins in the context of virus infection, as well as help in the development of antiviral drugs and protective vaccines.T he family Bunyaviridae is one of the largest taxonomic groupings of RNA viruses, containing over 350 named isolates that are classified into five genera: Hantavirus, Nairovirus, Orthobunyavirus, Phlebovirus, and Tospovirus (1). All viruses share a genome structure that comprises three segments of negative-sense or ambisense RNA, named small (S), medium (M), and large (L). The S segment encodes the nucleocapsid (N) protein; the M segment encodes the virion glycoproteins Gn and Gc; and the L segment encodes the L protein, the viral RNA-dependent RNA polymerase. Some viruses also encode nonstructural proteins on the S and M segments. Viruses that impinge on human health, either directly by causing human disease or indirectly by causing economic losses of domestic animals or crop plants, are found in each of the five gener...

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“…At present, there are three distinct genetic groups of TBPVs within the genus Phlebovirus, family Bunyaviridae (the SFTS group, the Bhanja group, and the Uukuniemi group) (3,4). The global distribution of these viruses is poorly understood, except for the local distributions of SFTSV and HRTV in their respective geographic areas where they are endemic (5)(6)(7)(8).…”

mentioning

confidence: 99%

“…Another reason why the TBPVs have been neglected could be the genetic divergence among different groups of TBPVs; for example, nucleotide sequence identities are 40 to 45% between the SFTS and Bhanja groups and only about 35% between the Uukuniemi group and the two other groups (3). This has hampered our ability to develop a single diagnostic tool for all TBPVs and has made it difficult to detect novel TBPVs using the existing tools.…”

mentioning

confidence: 99%

“…Recent advancements and increased availability of next-generation sequencing (NGS) technologies, which can read nucleotide sequences using sequence-independent amplification, allowed us to easily determine the genome sequences of several novel TBPVs. While all the complete genome sequences of TBPVs reported since the initial description of SFTSV in 2011 (1), HRTV (2), BHAV (3,21), Lone Star virus (22), Malsoor virus (23), Hunter Island virus (24), Khasan virus (25), Komandory virus (26), American dog tick phlebovirus, and blacklegged tick phlebovirus (27) were done using NGS, it would be technically difficult to apply this approach for largescale screening and field material, because of the cost and labor needed to produce sufficient reads of unknown pathogen sequences. Therefore, a detection system based on conventional reverse transcription-PCR (RT-PCR) that targets a wide range of TBPVs would be required for initial screening of samples prior to NGS.…”

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confidence: 99%

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Comprehensive Molecular Detection of Tick-Borne Phleboviruses Leads to the Retrospective Identification of Taxonomically Unassigned Bunyaviruses and the Discovery of a Novel Member of the Genus Phlebovirus

Matsuno

Weisend

Kajihara

et al. 2015

J Virol

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Until the recent emergence of two human-pathogenic tick-borne phleboviruses (TBPVs) (severe fever with thrombocytopenia syndrome virus [SFTSV] and Heartland virus), TBPVs have been neglected as causative agents of human disease. In particular, no studies have addressed the global distribution of TBPVs, and consequently, our understanding of the mechanism(s) underlying their evolution and emergence remains poor. In order to provide a useful tool for the ecological and epidemiological study of TBPVs, we have established a simple system that can detect all known TBPVs, based on conventional reverse transcription-PCR (RT-PCR) with degenerate primer sets targeting conserved regions of the viral L genome segment. Using this system, we have determined that several viruses that had been isolated from ticks decades ago but had not been taxonomically identified are novel TBPVs. Full-genome sequencing of these viruses revealed a novel fourth TBPV cluster distinct from the three known TBPV clusters (i.e., the SFTS, Bhanja, and Uukuniemi groups) and from the mosquito/sandfly-borne phleboviruses. Furthermore, by using tick samples collected in Zambia, we confirmed that our system had enough sensitivity to detect a new TBPV in a single tick homogenate. This virus, tentatively designated Shibuyunji virus after the region of tick collection, grouped into a novel fourth TBPV cluster. These results indicate that our system can be used as a first-line screening approach for TBPVs and that this kind of work will undoubtedly lead to the discovery of additional novel tick viruses and will expand our knowledge of the evolution and epidemiology of TBPVs. IMPORTANCETick-borne phleboviruses (TBPVs) have been largely neglected until the recent emergence of two virulent viruses, severe fever with thrombocytopenia syndrome virus and Heartland virus. Little is known about the global distribution of TBPVs or how these viruses evolved and emerged. A major hurdle to study the distribution of TBPVs is the lack of tools to detect these genetically divergent phleboviruses. In order to address this issue, we have developed a simple, rapid, and cheap RT-PCR system that can detect all known TBPVs and which led to the identification of several novel phleboviruses from previously uncharacterized tick-associated virus isolates. Our system can detect virus in a single tick sample and novel TBPVs that are genetically distinct from any of the known TBPVs. These results indicate that our system will be a useful tool for the surveillance of TBPVs and will facilitate understanding of the ecology of TBPVs. U ntil the recent emergence of two highly virulent humanpathogenic tick-borne phleboviruses (TBPVs), severe fever with thrombocytopenia syndrome virus (SFTSV) (1) and Heartland virus (HRTV) (2), the TBPVs were largely neglected as causative agents of human disease, whereas the mosquito-or sandflyborne phleboviruses, such as Rift Valley fever virus or Toscana virus, have been well studied. At present, there are three distinct genetic groups of TBPVs w...

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Characterization of the Bhanja Serogroup Viruses (Bunyaviridae): a Novel Species of the Genus Phlebovirus and Its Relationship with Other Emerging Tick-Borne Phleboviruses

Cited by 100 publications

References 37 publications

An emerging hemorrhagic fever in China caused by a novel bunyavirus SFTSV

An emerging hemorrhagic fever in China caused by a novel bunyavirus SFTSV

Reverse Genetics System for Severe Fever with Thrombocytopenia Syndrome Virus

Comprehensive Molecular Detection of Tick-Borne Phleboviruses Leads to the Retrospective Identification of Taxonomically Unassigned Bunyaviruses and the Discovery of a Novel Member of the Genus Phlebovirus

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