Because HIV-1 does not infect most nonhuman primates, animal modeling of human HIV infection and AIDS has primarily consisted of experimentally infecting macaques with related simian immunodeficiency viruses (SIVMAC). However, the usefulness of such models is limited by the substantial divergence between SIVMAC and HIV-1. We derived an HIV-1-based virus that includes only small portions of SIVMAC yet replicates robustly in both transformed and primary rhesus macaque T cells. Derivation of simian-tropic HIV-1 (stHIV-1) has important implications for understanding primate lentivirus zoonosis and should allow the development of improved animal models for studies of AIDS and the evaluation of vaccines and treatments.
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http://dx.doi.org/10.1126/science.1130994 | DOI Listing |
EBioMedicine
September 2023
AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA. Electronic address:
Front Cell Infect Microbiol
October 2020
Department of Microbiology, Tokushima University Graduate School of Medical Science, Tokushima, Japan.
Front Microbiol
May 2020
Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, United States.
The human-specific tropism of Human Immunodeficiency Virus Type 1 (HIV-1) has complicated the development of a macaque model of HIV-1 infection/AIDS that is suitable for preclinical evaluation of vaccines and novel treatment strategies. Several innate retroviral restriction factors, such as APOBEC3 family of proteins, TRIM5α, BST2, and SAMHD1, that prevent HIV-1 replication have been identified in macaque cells. Accessory proteins expressed by Simian Immunodeficiency virus (SIV) such as viral infectivity factor (Vif), viral protein X (Vpx), viral protein R (Vpr), and negative factor (Nef) have been shown to play key roles in overcoming these restriction factors in macaque cells.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
May 2019
Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065;
To replicate in a new host, lentiviruses must adapt to exploit required host factors and evade species-specific antiviral proteins. Understanding how host protein variation drives lentivirus adaptation allowed us to expand the host range of HIV-1 to pigtail macaques. We have previously derived a viral swarm (in the blood of infected animals) that can cause AIDS in this new host.
View Article and Find Full Text PDFAIDS Res Hum Retroviruses
May 2019
1 AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland.
Persistence of replication-competent viral reservoirs during infection remains a barrier to HIV cure, despite the ability of combination antiretroviral therapy (cART) to effectively suppress viral replication. Simian-tropic HIV (stHIV) is a minimally chimeric HIV-1 that is comprised of 94% HIV-1 sequence, contains HIV-1 drug and immunologic targets, and is capable of replicating to high levels and causing authentic HIV-like pathogenesis leading to clinical AIDS in pigtail macaques. Suppression of stHIV replication by cART provides a model for study of viral reservoirs and HIV-specific intervention strategies targeting them.
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