A chimeric measles virus with a lentiviral envelope replicates exclusively in CD4+/CCR5+ cells

Virology. 2011 Oct 25;419(2):117-25. doi: 10.1016/j.virol.2011.08.007. Epub 2011 Sep 3.

Abstract

We generated a replicating chimeric measles virus in which the hemagglutinin and fusion surface glycoproteins were replaced with the gp160 envelope glycoprotein of simian immunodeficiency virus (SIVmac239). Based on a previously cloned live-attenuated Schwarz vaccine strain of measles virus (MV), this chimera was rescued at high titers using reverse genetics in CD4+ target cells. Cytopathic effect consisted in the presence of large cell aggregates evolving to form syncytia, as observed during SIV infection. The morphology of the chimeric virus was identical to that of the parent MV particles. The presence of SIV gp160 as the only envelope protein on chimeric particles surface altered the cell tropism of the new virus from CD46+ to CD4+ cells. Used as an HIV candidate vaccine, this MV/SIVenv chimeric virus would mimic transient HIV-like infection, benefiting both from HIV-like tropism and the capacity of MV to replicate in dendritic cells, macrophages and lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Line
  • Chlorocebus aethiops
  • Fluorescent Antibody Technique
  • Gene Products, env / genetics*
  • Gene Products, env / metabolism
  • Giant Cells
  • Hemagglutinins, Viral / genetics
  • Humans
  • Macaca mulatta
  • Measles virus / genetics*
  • Measles virus / physiology*
  • Receptors, CCR5 / immunology
  • Receptors, CCR5 / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Simian Immunodeficiency Virus / genetics*
  • Simian Immunodeficiency Virus / metabolism
  • Viral Fusion Proteins / genetics
  • Virus Replication*

Substances

  • Gene Products, env
  • Hemagglutinins, Viral
  • Receptors, CCR5
  • Recombinant Fusion Proteins
  • SIV envelope glycoprotein gp160
  • Viral Fusion Proteins