Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder clade C HIV-1 envelopes

Virology. 2015 Jan 15:475:37-45. doi: 10.1016/j.virol.2014.10.032. Epub 2014 Nov 22.

Abstract

Simian-human immunodeficiency viruses (SHIVs) that mirror natural transmitted/founder (T/F) viruses in man are needed for evaluation of HIV-1 vaccine candidates in nonhuman primates. Currently available SHIVs contain HIV-1 env genes from chronically-infected individuals and do not reflect the characteristics of biologically relevant HIV-1 strains that mediate human transmission. We chose to develop clade C SHIVs, as clade C is the major infecting subtype of HIV-1 in the world. We constructed 10 clade C SHIVs expressing Env proteins from T/F viruses. Three of these ten clade C SHIVs (SHIV KB9 C3, SHIV KB9 C4 and SHIV KB9 C5) replicated in naïve rhesus monkeys. These three SHIVs are mucosally transmissible and are neutralized by sCD4 and several HIV-1 broadly neutralizing antibodies. However, like natural T/F viruses, they exhibit low Env reactivity and a Tier 2 neutralization sensitivity. Of note, none of the clade C T/F SHIVs elicited detectable autologous neutralizing antibodies in the infected monkeys, even though antibodies that neutralized a heterologous Tier 1 HIV-1 were generated. Challenge with these three new clade C SHIVs will provide biologically relevant tests for vaccine protection in rhesus macaques.

Keywords: HIV-1 Clade C; Mucosal transmission; SHIV; Transmitted/founder Env.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation, Viral / physiology
  • HEK293 Cells
  • HIV-1 / genetics*
  • Humans
  • Mutation
  • Phylogeny
  • Simian Acquired Immunodeficiency Syndrome / virology*
  • Simian Immunodeficiency Virus / genetics*
  • Viral Envelope Proteins / metabolism*
  • Viremia

Substances

  • Viral Envelope Proteins