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Evidence of human infection by a new mammarenavirus endemic to Southeastern Asia.

ABSTRACT: Southeastern Asia is a recognised hotspot for emerging infectious diseases, many of which have an animal origin. Mammarenavirus infections contribute significantly to the human disease burden in both Africa and the Americas, but little data exists for Asia. To date only two mammarenaviruses, the widely spread lymphocytic choriomeningitis virus and the recently described W?nzh?u virus have been identified in this region, but the zoonotic impact in Asia remains unknown. Here we report the presence of a novel mammarenavirus and of a genetic variant of the W?nzh?u virus and provide evidence of mammarenavirus-associated human infection in Asia. The association of these viruses with widely distributed mammals of diverse species, commonly found in human dwellings and in peridomestic habitats, illustrates the potential for widespread zoonotic transmission and adds to the known aetiologies of infectious diseases for this region.

SUBMITTER: Blasdell KR

PROVIDER: S-EPMC4900801 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Evidence of human infection by a new mammarenavirus endemic to Southeastern Asia.

Blasdell Kim R KR Duong Veasna V Eloit Marc M Chretien Fabrice F Ly Sowath S Hul Vibol V Deubel Vincent V Morand Serge S Buchy Philippe P

eLife 20160609

Southeastern Asia is a recognised hotspot for emerging infectious diseases, many of which have an animal origin. Mammarenavirus infections contribute significantly to the human disease burden in both Africa and the Americas, but little data exists for Asia. To date only two mammarenaviruses, the widely spread lymphocytic choriomeningitis virus and the recently described Wēnzhōu virus have been identified in this region, but the zoonotic impact in Asia remains unknown. Here we report the presence ...[more]

PMID: 27278118

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Project description:The New World mammarenavirus Tacaribe virus (TCRV) has been isolated from fruit bats, mosquitoes, and ticks, whereas all other known New World mammarenaviruses are maintained in rodents. TCRV has not been linked to human disease, but it has been shown to protect against Argentine hemorrhagic fever-like disease in marmosets infected with the New World mammarenavirus Junín virus (JUNV), indicating the potential of TCRV as a live-attenuated vaccine for the treatment of Argentine hemorrhagic fever. Implementation of TCRV as a live-attenuated vaccine or a vaccine vector would be facilitated by the establishment of reverse genetics systems for the genetic manipulation of the TCRV genome. In this study, we developed, for the first time, reverse genetics approaches for the generation of recombinant TCRV (rTCRV). We successfully rescued a wild-type (WT) rTCRV (a trisegmented form of TCRV expressing two reporter genes [r3TCRV]) and a bisegmented TCRV expressing a single reporter gene from a bicistronic viral mRNA (rTCRV/GFP). These reverse genetics approaches represent an excellent tool to investigate the biology of TCRV and to explore its potential use as a live-attenuated vaccine or a vaccine vector for the treatment of other viral infections. Notably, we identified a 39-nucleotide (nt) deletion (?39) in the noncoding intergenic region (IGR) of the viral large (L) segment that is required for optimal virus multiplication. Accordingly, an rTCRV containing this 39-nt deletion in the L-IGR (rTCRV/?39) exhibited decreased viral fitness in cultured cells, suggesting the feasibility of using this deletion in the L-IGR as an approach to attenuate TCRV, and potentially other mammarenaviruses, for their implementation as live-attenuated vaccines or vaccine vectors.IMPORTANCE To date, no Food and Drug Administration (FDA)-approved vaccines are available to combat hemorrhagic fever caused by mammarenavirus infections in humans. Treatment of mammarenavirus infections is limited to the off-label use of ribavirin, which is partially effective and associated with significant side effects. Tacaribe virus (TCRV), the prototype member of the New World mammarenaviruses, is nonpathogenic in humans but able to provide protection against Junín virus (JUNV), the causative agent of Argentine hemorrhagic fever, demonstrating the feasibility of using TCRV as a live-attenuated vaccine vector for the treatment of JUNV and potentially other viral infections. Here, we describe for the first time the feasibility of generating recombinant TCRV (rTCRV) using reverse genetics approaches, which paves the way to study the biology of TCRV and also its potential use as a live-attenuated vaccine or a vaccine vector for the treatment of mammarenavirus and/or other viral infections in humans.

Dataset Information

Evidence of human infection by a new mammarenavirus endemic to Southeastern Asia.

Publications

Evidence of human infection by a new mammarenavirus endemic to Southeastern Asia.

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