Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins

Gregory Q. Del Prete, Braiden Ailers, Brian Moldt, Brandon F. Keele, Jacob D. Estes, Anthony Rodriguez, Marissa Sampias, Kelli Oswald, Randy Fast, Charles M. Trubey, Elena Chertova, Jeremy Smedley, Celia C. Labranche, David C. Montefiori, Dennis R. Burton, George M. Shaw, Marty Markowitz, Michael Piatak, Vineet N. Kewalramani, Paul D. BieniaszJeffrey D. Lifson, Theodora Hatziioannou

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge.

Original languageEnglish (US)
Pages (from-to)412-418
Number of pages7
JournalCell Host and Microbe
Volume16
Issue number3
DOIs
StatePublished - Sep 10 2014

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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    Del Prete, G. Q., Ailers, B., Moldt, B., Keele, B. F., Estes, J. D., Rodriguez, A., Sampias, M., Oswald, K., Fast, R., Trubey, C. M., Chertova, E., Smedley, J., Labranche, C. C., Montefiori, D. C., Burton, D. R., Shaw, G. M., Markowitz, M., Piatak, M., Kewalramani, V. N., ... Hatziioannou, T. (2014). Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins. Cell Host and Microbe, 16(3), 412-418. https://doi.org/10.1016/j.chom.2014.08.003