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Macaque-tropic human immunodeficiency virus type 1: breaking out of the host restriction factors
Akatsuki Saito1, Hirofumi Akari
1Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University Inuyama, Japan ; Japan Foundation for AIDS Prevention Chiyoda-ku, Japan.
Abstract:
Macaque monkeys serve as important animal models for understanding the pathogenesis of lentiviral infections. Since human immunodeficiency virus type 1 (HIV-1) hardly replicates in macaque cells, simian immunodeficiency virus (SIV) or chimeric viruses between HIV-1 and SIV (SHIV) have been used as challenge viruses in this research field. These viruses, however, are genetically distant from HIV-1. Therefore, in order to evaluate the efficacy of anti-HIV-1 drugs and vaccines in macaques, the development of a macaque-tropic HIV-1 (HIV-1mt) having the ability to replicate efficiently in macaques has long been desired. Recent studies have demonstrated that host restriction factors, such as APOBEC3 family and TRIM5, impose a strong barrier against HIV-1 replication in macaque cells. By evading these restriction factors, others and we have succeeded in developing an HIV-1mt that is able to replicate in macaques. In this review, we have attempted to shed light on the role of host factors that affect the susceptibility of macaques to HIV-1mt infection, especially by focusing on TRIM5-related factors.
Insights
Researchers developed macaque-tropic human immunodeficiency virus type 1 (HIV-1mt) for better vaccine and drug testing. This breakthrough overcomes host restriction factors, enabling efficient HIV-1 replication in macaques.
Area of Science:
- Virology
- Immunology
- Primatology
Background:
- Macaque models are crucial for lentiviral infection studies.
- Human immunodeficiency virus type 1 (HIV-1) poorly replicates in macaques, limiting research.
- Simian immunodeficiency virus (SIV) and SHIV are used but are genetically distant from HIV-1.
Purpose of the Study:
- To develop a macaque-tropic HIV-1 (HIV-1mt) for efficient replication in macaques.
- To enable better evaluation of anti-HIV-1 drugs and vaccines in macaque models.
- To investigate host factors influencing macaque susceptibility to HIV-1mt.
Main Methods:
- Overcoming host restriction factors like APOBEC3 and TRIM5.
- Developing genetically modified HIV-1 strains (HIV-1mt) for macaque tropism.
- Analyzing host-pathogen interactions in macaque lentiviral infection models.
Main Results:
- Successfully created an HIV-1mt capable of efficient replication in macaques.
- Demonstrated that evasion of host restriction factors is key to macaque tropism.
- Identified TRIM5-related factors as significant in macaque susceptibility to HIV-1mt.
Conclusions:
- The developed HIV-1mt is a valuable tool for preclinical studies of HIV-1 therapies.
- Understanding host restriction factors like TRIM5 is critical for lentiviral vector development.
- This advancement facilitates more accurate assessment of HIV-1 interventions in a relevant animal model.
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