Details

Autor(en) / Beteiligte

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

Titel

Selection of Unadapted, Pathogenic SHIVs Encoding Newly Transmitted HIV-1 Envelope Proteins

Ist Teil von

• Cell host & microbe, 2014-09, Vol.16 (3), p.412-418

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

ScienceDirect

Beschreibungen/Notizen

• 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. [Display omitted] •Large numbers of SIVMAC expressing transmitted HIV-1 Env proteins (SHIVs) were generated•SHIVs that replicate best in macaques were selected after inoculation with virus pools•Selected SHIVs cause AIDS without requiring adaptation in animals•A broadly neutralizing antibody protects against mucosal challenge with a selected SHIV SIVMAC expressing HIV-1 envelopes (SHIVs) are used to model AIDS in monkeys, but the available SHIVs are extensively adapted. Del Prete et al. generated SHIVs expressing newly transmitted HIV-1 envelope proteins and screened virus pools in monkeys to select unadapted SHIVs that cause AIDS. Their utility for immunoprophylactic studies is demonstrated.