Elsevier

Virology

Volume 476, February 2015, Pages 85-91
Virology

Brief Communication
Recombinant Marburg viruses containing mutations in the IID region of VP35 prevent inhibition of Host immune responses

https://doi.org/10.1016/j.virol.2014.12.002Get rights and content
Under a Creative Commons license
open access

Highlights

  • Recombinant Marburg viruses carrying mutations in the CBP of VP35 were rescued

  • Mutant MARVs exhibit attenuated growth in interferon-competent cells

  • Mutant MARVs were unable to inhibit expression of various antiviral genes

  • A common VP35-mediated immune-modulatory strategy is suggested for filoviruses.

Abstract

Previous in vitro studies have demonstrated that Ebola and Marburg virus (EBOV and MARV) VP35 antagonize the host cell immune response. Moreover, specific mutations in the IFN inhibitory domain (IID) of EBOV and MARV VP35 that abrogate their interaction with virus-derived dsRNA, lack the ability to inhibit the host immune response. To investigate the role of MARV VP35 in the context of infectious virus, we used our reverse genetics system to generate two recombinant MARVs carrying specific mutations in the IID region of VP35. Our data show that wild-type and mutant viruses grow to similar titers in interferon deficient cells, but exhibit attenuated growth in interferon-competent cells. Furthermore, in contrast to wild-type virus, both MARV mutants were unable to inhibit expression of various antiviral genes. The MARV VP35 mutants exhibit similar phenotypes to those previously described for EBOV, suggesting the existence of a shared immune-modulatory strategy between filoviruses.

Keywords

Filovirus
Marburg virus
Bat virus
VP35
IFN-antagonism
Central basic
Patch
Immune-modulatory
Ebola virus

Cited by (0)

The findings and conclusions in this report are ours and do not necessarily represent the views of the Centers for Disease Control and Prevention.