Development of a reverse genetics system for Sosuga virus allows rapid screening of antiviral compounds

Welch, Stephen R.; Chakrabarti, Ayan K.; Wiggleton Guerrero, Lisa; Jenks, Harley M.; Lo, Michael K.; Nichol, Stuart T.; Spiropoulou, Christina F.; Albariño, César G.

doi:10.1371/journal.pntd.0006326

Development of a reverse genetics system for Sosuga virus allows rapid screening of antiviral compounds

Journal Article · Fri Mar 09 00:00:00 EST 2018 · PLoS Neglected Tropical Diseases (Online)

DOI:https://doi.org/10.1371/journal.pntd.0006326· OSTI ID:1904892

^[1]; Chakrabarti, Ayan K. ^[2]; Wiggleton Guerrero, Lisa ^[2]; Jenks, Harley M. ^[2]; ^[2]; Nichol, Stuart T. ^[2]; ^[2]; Albariño, César G. ^[2]

Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States); OSTI
Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States)

Sosuga virus (SOSV) is a recently discovered zoonotic paramyxovirus isolated from a single human case in 2012; it has been ecologically and epidemiologically associated with transmission by the Egyptian rousette bat (Rousettus aegyptiacus). Bats have long been recognized as sources of novel zoonotic pathogens, including highly lethal paramyxoviruses like Nipah virus (NiV) and Hendra virus (HeV). The ability of SOSV to cause severe human disease supports the need for studies on SOSV pathogenesis to better understand the potential impact of this virus and to identify effective treatments. Here we describe a reverse genetics system for SOSV comprising a minigenome-based assay and a replication-competent infectious recombinant reporter SOSV that expresses the fluorescent protein ZsGreen1 in infected cells. First, we used the minigenome assay to rapidly screen for compounds inhibiting SOSV replication at biosafety level 2 (BSL-2). The antiviral activity of candidate compounds was then tested against authentic viral replication using the reporter SOSV at BSL-3. We identified several compounds with anti-SOSV activity, several of which also inhibit NiV and HeV. Alongside its utility in screening for potential SOSV therapeutics, the reverse genetics system described here is a powerful tool for analyzing mechanisms of SOSV pathogenesis, which will facilitate our understanding of how to combat the potential public health threats posed by emerging bat-borne paramyxoviruses.

View Accepted Manuscript (DOE)

Research Organization:: Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States); Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: Centers for Disease Control and Prevention (CDC); USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 1904892

Journal Information:: PLoS Neglected Tropical Diseases (Online), Journal Name: PLoS Neglected Tropical Diseases (Online) Journal Issue: 3 Vol. 12; ISSN 1935-2735

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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Development of a reverse genetics system for Sosuga virus allows rapid screening of antiviral compounds

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