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.

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.1130994DOI Listing

Publication Analysis

Top Keywords

simian-tropic hiv-1
8
generation simian-tropic
4
hiv-1
4
hiv-1 restriction
4
restriction factor
4
factor evasion
4
evasion hiv-1
4
hiv-1 infect
4
infect nonhuman
4
nonhuman primates
4

Similar Publications

Long-acting lenacapavir protects macaques against intravenous challenge with simian-tropic HIV.

EBioMedicine

September 2023

AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA. Electronic address:

Article Synopsis
  • - The study investigates the efficacy of long-acting lenacapavir (LEN), an FDA-approved HIV capsid inhibitor, for pre-exposure prophylaxis (PrEP) using a simian model of HIV infection in pigtail macaques.
  • - Experimentation revealed that LEN demonstrated strong antiviral activity in vitro and maintained effective plasma levels in vivo, providing protection against HIV infection when administered before exposure.
  • - The results suggest that LEN could be a valuable option for PrEP in humans, reinforcing the relevance of the simian model in HIV research.
View Article and Find Full Text PDF

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 PDF

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 PDF

Short Communication: Ultrasensitive Immunoassay for Assessing Residual Simian-Tropic HIV in Nonhuman Primate Models of AIDS.

AIDS 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.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!