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Cell Host Microbe. 2014 Sep 10;16(3):412-8. doi: 10.1016/j.chom.2014.08.003.

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

Author information

1
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA.
2
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.
3
Department of Immunology and Microbiology, International AIDS Vaccine Initiative Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
4
Laboratory Animal Sciences Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA.
5
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
6
Department of Immunology and Microbiology, International AIDS Vaccine Initiative Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
7
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
8
HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA.
9
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA; Laboratory of Retrovirology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10016, USA.
10
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA. Electronic address: lifsonj@mail.nih.gov.
11
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA. Electronic address: thatziio@adarc.org.

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.

PMID:
25211081
PMCID:
PMC4268878
DOI:
10.1016/j.chom.2014.08.003
[Indexed for MEDLINE]
Free PMC Article

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