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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Asmal, M; Luedemann, C; Lavine, CL; Mach, LV; Balachandran, H; Brinkley, C; Denny, TN; Lewis, MG; Anderson, H; Pal, R; Sok, D; Le, K; Pauthner, M; Hahn, BH; Shaw, GM; Seaman, MS; Letvin, NL; Burton, DR; Sodroski, JG; Haynes, BF; Santra, S

Published Date

  • January 2015

Published In

Volume / Issue

  • 475 /

Start / End Page

  • 37 - 45

PubMed ID

  • 25462344

Pubmed Central ID

  • 25462344

Electronic International Standard Serial Number (EISSN)

  • 1096-0341

International Standard Serial Number (ISSN)

  • 0042-6822

Digital Object Identifier (DOI)

  • 10.1016/j.virol.2014.10.032

Language

  • eng