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

PLoS Negl Trop Dis. 2018 Mar 9;12(3):e0006326. doi: 10.1371/journal.pntd.0006326. eCollection 2018 Mar.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Chiroptera / virology
  • Humans
  • Paramyxoviridae / genetics*
  • Paramyxoviridae / physiology
  • Paramyxoviridae Infections / virology
  • Reverse Genetics / methods*
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents

Grants and funding

The study was funded by CDC (HHS, US Government). Stephen Welch holds a fellowship supported by ORISE through an interagency agreement between the U.S. DOE and CDC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.