Novel Phlebovirus with Zoonotic Potential Isolated from Ticks, Australia

Wang, Jianning; Selleck, Paul; Yu, Meng; Ha, Wendy; Rootes, Chrissy; Gales, Rosemary; Wise, Terry G.; Crameri, Sandra; Chen, Honglei; Broz, Ivano; Hyatt, Alex D.; Woods, Rupert; Meehan, Brian; McCullough, Sam; Wang, Lin‐Fa

doi:10.3201/eid2006.140003

Cited by 83 publications

(62 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A novel phlebovirus called Malsoor virus that is phylogenetically related to SFTSV and HRTV has been reported from bats in India (30); whether Malsoor virus is tick borne is not known. Lastly, Hunter Island Group virus has been isolated from ticks associated with shy albatrosses in Australia (31). The zoonotic potential of these viruses (Malsoor and Hunter Island Group viruses) is unknown.…”

mentioning

confidence: 99%

Reverse Genetics System for Severe Fever with Thrombocytopenia Syndrome Virus

Brennan

Zhang

et al. 2015

J Virol

View full text Add to dashboard Cite

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...

show abstract

mentioning

confidence: 99%

Reverse Genetics System for Severe Fever with Thrombocytopenia Syndrome Virus

Brennan

Zhang

et al. 2015

J Virol

View full text Add to dashboard Cite

show abstract

“…Its investigation has led to major insights into many aspects of the phlebovirus life cycle, for example virion structure and morphogenesis, cell entry and viral replication [23][24][25][26][27][28][29][30][31][32]. Recently, a number of novel tick-borne phleboviruses, all closely related to UUKV, have emerged in distinct parts of the world, some of which are highly pathogenic in humans [33][34][35][36][37][38][39][40][41]. Recent illustrations are Heartland virus (HRTV) in North America and severe fever with thrombocytopenia virus (SFTSV) in Asia, latter causing a fatality rate of up to 60% in some outbreaks [33][34][35][36][37]40].…”

Section: A Global Threat To Human and Veterinary Public Healthmentioning

confidence: 99%

Bunyaviruses: From Transmission by Arthropods to Virus Entry into the Mammalian Host First-Target Cells

Léger

Lozach

2015

Future Virol.

View full text Add to dashboard Cite

The Bunyaviridae constitute a large family of animal RNA viruses distributed worldwide, most members of which are transmitted to vertebrate hosts by arthropods and can cause severe pathologies in humans and livestock. With an increasing number of outbreaks, arthropod-borne bunyaviruses (arbo-bunyaviruses) present a global threat to public health and agricultural productivity. Yet transmission, tropism, receptors and cell entry remain poorly characterized. The focus of this review is on the initial infection of mammalian hosts by arbo-bunyaviruses from cellular and molecular perspectives, with particular attention to the human host. We address current knowledge and advances regarding the identity of the first-target cells and the subsequent processes of entry and penetration into the cytosol. Aspects of the vector-to-host switch that influence the early steps of cell infection in mammalian skin, where incoming particles are introduced by infected arthropods, are also highlighted and discussed.

show abstract

“…Although human cases caused by SFTS virus have only been reported in Asia, the recent emergence of another tick-borne phlebovirus, Heartland virus, a close relative of SFTS virus, responsible for serious and fatal cases in the United States (3,42), and the recognition of another tick-borne phlebovirus with zoonotic potential in Australia (43), named Hunter samples were collected at each step of the purification process for evaluation by plaque assay. The sample resulting from the immune-selection step using anti-CD63 beads is depicted in the figure as the CD63 selected, whereas those resulting from the subsequent immune-(negative) selection step are shown as the CD63/SFTSV selected.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Mediate Receptor-Independent Transmission of Novel Tick-Borne Bunyavirus

Silvas

Popov

Paulucci-Holthauzen

et al. 2016

J Virol

View full text Add to dashboard Cite

Severe fever with thrombocytopenia syndrome (SFTS) virus is a newly recognized member of the genus Phlebovirus in the family Bunyaviridae. The virus was isolated from patients presenting with hemorrhagic manifestations and an initial case fatality rate of 12 to 30% was reported. Due to the recent emergence of this pathogen, there is limited knowledge on the molecular virology of SFTS virus. Recently, we reported that the SFTS virus NSs protein inhibited the activation of the beta interferon (IFN-␤) promoter. Furthermore, we also found that SFTS virus NSs relocalizes key components of the IFN response into NSs-induced cytoplasmic structures. Due to the important role these structures play during SFTS virus replication, we conducted live cell imaging studies to gain further insight into the role and trafficking of these cytoplasmic structures during virus infection. We found that some of the SFTS virus NSs-positive cytoplasmic structures were secreted to the extracellular space and endocytosed by neighboring cells. We also found that these secreted structures isolated from NSs-expressing cells and SFTS virus-infected cells were positive for the viral protein NSs and the host protein CD63, a protein associated with extracellular vesicles. Electron microscopy studies also revealed that the isolated CD63-immunoprecipitated extracellular vesicles produced during SFTS virus infection contained virions. The virions harbored within these structures were efficiently delivered to uninfected cells and were able to sustain SFTS virus replication. Altogether, these results suggest that SFTS virus exploits extracellular vesicles to mediate virus receptor-independent transmission to host cells and open the avenue for novel therapeutic strategies against SFTS virus and related pathogens. IMPORTANCESFTS virus is novel bunyavirus associated with hemorrhagic fever illness. Currently, limited information is available about SFTS virus. In the present study, we demonstrated that extracellular vesicles produced by SFTS virus-infected cells harbor infectious virions. We sought to determine whether these "infectious" extracellular vesicles can mediate transmission of the virus and confirmed that the SFTS virions were efficiently transported by these secreted structures into uninfected cells and were able to sustain efficient replication of SFTS virus. These results have significant impact on our understanding of how the novel tick-borne phleboviruses hijack cellular machineries to establish infection and point toward a novel mechanism for virus replication among arthropod-borne viruses. The Bunyaviridae family comprises five genera, including Orthobunyavirus, Phlebovirus, Nairovirus, Hantavirus, and Tospovirus. The majority of viruses within this family (with the exception of Hantaviruses) are considered arthropod-borne viruses and are important causes of morbidity and mortality around the world. These viruses are associated with a range of clinical symptoms characterized by febrile illness and in the most severe cases fatal hepa...

show abstract

Novel Phlebovirus with Zoonotic Potential Isolated from Ticks, Australia

Cited by 83 publications

References 12 publications

Reverse Genetics System for Severe Fever with Thrombocytopenia Syndrome Virus

Reverse Genetics System for Severe Fever with Thrombocytopenia Syndrome Virus

Bunyaviruses: From Transmission by Arthropods to Virus Entry into the Mammalian Host First-Target Cells

Extracellular Vesicles Mediate Receptor-Independent Transmission of Novel Tick-Borne Bunyavirus

Contact Info

Product

Resources

About