A single mutation (V64G) within the RING Domain of Z attenuates Junin virus.

Autor: Steven J Hallam, John T Manning, Junki Maruyama, Alexey Seregin, Cheng Huang, David H Walker, Juan Carlos de la Torre, Slobodan Paessler
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: PLoS Neglected Tropical Diseases, Vol 14, Iss 9, p e0008555 (2020)
Druh dokumentu: article
ISSN: 1935-2727
1935-2735
DOI: 10.1371/journal.pntd.0008555
Popis: Junin virus (JUNV) is a New World arenavirus that is the causative agent of Argentine hemorrhagic fever (AHF). Candid#1 (Can) is a live-attenuated vaccine strain of JUNV that since its introduction has resulted in a marked decrease in AHF incidence within the endemic regions of the Pampas in Argentina. Originally, the viral determinants and mechanisms of Can attenuation were not well understood. Recent work has identified the glycoprotein as the major attenuating factor for Can. The establishment of attenuating strategies based on any of the other viral proteins, however, has not been pursued. Here, we document the role of Can Z resulting in incompatibilities with wild type JUNV that results in decreased growth in vitro. In addition, this incompatibility results in attenuation of the virus in the guinea pig model. Further, we identify a single mutation (V64G) in the Z protein that is able to confer this demonstrated attenuation. By establishing and characterizing a novel attenuation strategy for New World mammarenaviruses, we hope to aid future vaccine development for related emerging pathogens including Machupo virus (MACV), Guanarito virus (GTOV), and Sabia virus (SABV).
Databáze: Directory of Open Access Journals
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