Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins.
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.
Duke Scholars
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- env Gene Products, Human Immunodeficiency Virus
- Virus Cultivation
- Simian immunodeficiency virus
- Simian Immunodeficiency Virus
- Simian Acquired Immunodeficiency Syndrome
- Macaca
- Immunology
- Humans
- HIV-1
- HIV Infections
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- env Gene Products, Human Immunodeficiency Virus
- Virus Cultivation
- Simian immunodeficiency virus
- Simian Immunodeficiency Virus
- Simian Acquired Immunodeficiency Syndrome
- Macaca
- Immunology
- Humans
- HIV-1
- HIV Infections