Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins.
Journal Article (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.
- Del Prete, GQ; Eilers, 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
- September 10, 2014
Volume / Issue
- 16 / 3
Start / End Page
- 412 - 418
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)
- United States