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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Del Prete, GQ; Ailers, B; Moldt, B; Keele, BF; Estes, JD; Rodriguez, A; Sampias, M; Oswald, K; Fast, R; Trubey, CM; Chertova, E; Smedley, J; LaBranche, CC; Montefiori, DC; Burton, DR; Shaw, GM; Markowitz, M; Piatak, M; KewalRamani, VN; Bieniasz, PD; Lifson, JD; Hatziioannou, T

Published Date

  • September 10, 2014

Published In

Volume / Issue

  • 16 / 3

Start / End Page

  • 412 - 418

PubMed ID

  • 25211081

Pubmed Central ID

  • 25211081

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2014.08.003

Language

  • eng

Conference Location

  • United States