Reverse genetics of Mononegavirales: How they work, new vaccines, and new cancer therapeutics

Virology. 2015 May:479-480:331-44. doi: 10.1016/j.virol.2015.01.029. Epub 2015 Feb 18.

Abstract

The order Mononegavirales includes five families: Bornaviridae, Filoviridae, Nyamaviridae, Paramyxoviridae, and Rhabdoviridae. The genome of these viruses is one molecule of negative-sense single strand RNA coding for five to ten genes in a conserved order. The RNA is not infectious until packaged by the nucleocapsid protein and transcribed by the polymerase and co-factors. Reverse genetics approaches have answered fundamental questions about the biology of Mononegavirales. The lack of icosahedral symmetry and modular organization in the genome of these viruses has facilitated engineering of viruses expressing fluorescent proteins, and these fluorescent proteins have provided important insights about the molecular and cellular basis of tissue tropism and pathogenesis. Studies have assessed the relevance for virulence of different receptors and the interactions with cellular proteins governing the innate immune responses. Research has also analyzed the mechanisms of attenuation. Based on these findings, ongoing clinical trials are exploring new live attenuated vaccines and the use of viruses re-engineered as cancer therapeutics.

Keywords: Attenuation; Cancer therapy; Innate immunity; Mononegavirales; Pathology; Receptors; Reverse genetics; Tropism; Vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Host-Pathogen Interactions
  • Humans
  • Mononegavirales / genetics*
  • Mononegavirales / pathogenicity
  • Mononegavirales / physiology*
  • Neoplasms / therapy
  • Oncolytic Virotherapy / methods
  • Reverse Genetics*
  • Vaccines, Attenuated / immunology
  • Vaccines, Attenuated / isolation & purification
  • Viral Tropism
  • Viral Vaccines / immunology
  • Viral Vaccines / isolation & purification
  • Virus Assembly
  • Virus Replication

Substances

  • Vaccines, Attenuated
  • Viral Vaccines