Risk analysis of inter-species reassortment through a Rift Valley fever phlebovirus MP-12 vaccine strain

PLoS One. 2017 Sep 19;12(9):e0185194. doi: 10.1371/journal.pone.0185194. eCollection 2017.

Abstract

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula. The causative agent, Rift Valley fever phlebovirus (RVFV), belongs to the genus Phlebovirus in the family Phenuiviridae and causes high rates of abortions in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral maintenance by mosquito vectors has led to sporadic RVF outbreaks in ruminants and humans in endemic countries, and effective vaccination of animals and humans may minimize the impact of this disease. A live-attenuated MP-12 vaccine strain is one of the best characterized RVFV strains, and was conditionally approved as a veterinary vaccine in the U.S. Live-attenuated RVF vaccines including MP-12 strain may form reassortant strains with other bunyavirus species. This study thus aimed to characterize the occurrence of genetic reassortment between the MP-12 strain and bunyavirus species closely related to RVFV. The Arumowot virus (AMTV) and Gouleako goukovirus (GOLV), are transmitted by mosquitoes in Africa. The results of this study showed that GOLV does not form detectable reassortant strains with the MP-12 strain in co-infected C6/36 cells. The AMTV also did not form any reassortant strains with MP-12 strain in co-infected C6/36 cells, due to the incompatibility among N, L, and Gn/Gc proteins. A lack of reassortant formation could be due to a functional incompatibility of N and L proteins derived from heterologous species, and due to a lack of packaging via heterologous Gn/Gc proteins. The MP-12 strain did, however, randomly exchange L-, M-, and S-segments with a genetic variant strain, rMP12-GM50, in culture cells. The MP-12 strain is thus unlikely to form any reassortant strains with AMTV or GOLV in nature.

MeSH terms

  • Animals
  • Base Sequence
  • Chlorocebus aethiops
  • Genotype
  • Humans
  • Phlebovirus / genetics
  • Phlebovirus / physiology*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Reassortant Viruses / genetics
  • Reassortant Viruses / physiology
  • Rift Valley Fever / prevention & control
  • Rift Valley Fever / virology
  • Rift Valley fever virus / genetics
  • Rift Valley fever virus / physiology*
  • Vero Cells
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism
  • Virus Replication

Substances

  • RNA, Viral
  • Viral Nonstructural Proteins

Grants and funding

This study was made possible by the generous support of the subcontract 26-3002-6062 from the American people through the United States Agency for International Development (USAID, AID-OAA-A-13-00084, http://research.utep.edu/Default.aspx?alias=research.utep.edu/riftvalleyfeverinnovationlab). The study was also partially supported by the Kansas Bioscience Authority (http://www.kansasbioauthority.org/) grant subcontract S13027, the NIH/NIAID (https://www.niaid.nih.gov/) grant R01 AI08764301-A1, and the funding from the Sealy Center for Vaccine Development at the University of Texas Medical Branch at Galveston (https://www.utmb.edu/scvd/). SN was supported by the James W. McLaughlin Postdoctoral Fellowship at UTMB (https://www.utmb.edu/mclaughlin/index.htm). The contents do not necessarily reflect the views of USAID or the United States Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.