Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections

Mohammed Asmal, Sophie Lane, Meijuan Tian, Gabrielle Nickel, Colin Venner, Brennan Dirk, Jimmy Dikeakos, Corinne Luedemann, Linh Mach, Harikrishnan Balachandran, Adam Buzby, Srinivas Rao, Norman Letvin, Yong Gao, Eric J. Arts

Research output: Contribution to journalArticle

Abstract

For studies on vaccines and therapies for HIV disease, SIV-HIV chimeric viruses harboring the HIV-1 env gene (SHIVenv) remain the best virus in non-human primate models. However, there are still very few SHIVenv viruses that can cause AIDS in non-CD8-depleted animals. In the present study, a recently created CCR5-using SHIVenv_B3 virus with env gene derived from acute/early HIV-1 infections (AHI) successfully established pathogenic infection in macaques. Through a series of investigations on the evolution, mutational profile, and phenotype of the virus and the resultant humoral immune response in infected rhesus macaques, we found that the E32K mutation in the Env C1 domain was associated with macaque pathogenesis, and that the electrostatic interactions in Env may favor E32K at the gp120 N terminus and “lock” the binding to heptad repeat 1 of gp41 in the trimer and produce a SHIVenv with increased fitness and pathogenesis during macaque infections.

Original languageEnglish (US)
Pages (from-to)298-312
Number of pages15
JournalVirology
Volume499
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

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Macaca mulatta
HIV Infections
HIV-1
HIV
Viruses
Macaca
env Genes
Infection
Genes
Active Immunotherapy
Humoral Immunity
Static Electricity
Primates
Acquired Immunodeficiency Syndrome
Phenotype
Mutation

Keywords

  • Envelope
  • Pathogenesis
  • Rhesus macaque
  • SIV-HIV chimeric viruses

ASJC Scopus subject areas

  • Virology

Cite this

Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. / Asmal, Mohammed; Lane, Sophie; Tian, Meijuan; Nickel, Gabrielle; Venner, Colin; Dirk, Brennan; Dikeakos, Jimmy; Luedemann, Corinne; Mach, Linh; Balachandran, Harikrishnan; Buzby, Adam; Rao, Srinivas; Letvin, Norman; Gao, Yong; Arts, Eric J.

In: Virology, Vol. 499, 01.12.2016, p. 298-312.

Research output: Contribution to journalArticle

Asmal, M, Lane, S, Tian, M, Nickel, G, Venner, C, Dirk, B, Dikeakos, J, Luedemann, C, Mach, L, Balachandran, H, Buzby, A, Rao, S, Letvin, N, Gao, Y & Arts, EJ 2016, 'Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections', Virology, vol. 499, pp. 298-312. https://doi.org/10.1016/j.virol.2016.09.021
Asmal, Mohammed ; Lane, Sophie ; Tian, Meijuan ; Nickel, Gabrielle ; Venner, Colin ; Dirk, Brennan ; Dikeakos, Jimmy ; Luedemann, Corinne ; Mach, Linh ; Balachandran, Harikrishnan ; Buzby, Adam ; Rao, Srinivas ; Letvin, Norman ; Gao, Yong ; Arts, Eric J. / Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections. In: Virology. 2016 ; Vol. 499. pp. 298-312.
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