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Molecular cloning and anti-HIV-1 activities of APOBEC3s from northern pig-tailed macaques (Macaca leonina)
Xiao-Liang Zhang1, Jia-Hao Song2, Wei Pang3
1Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming Yunnan 650223, China;Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming Yunnan 650500, China.
Abstract:
Northern pig-tailed macaques (NPMs, Macaca leonina) are susceptible to HIV-1 infection largely due to the loss of HIV-1-restricting factor TRIM5α. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host. The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences (CDSs) showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques. We further analyzed the anti-HIV-1 activities of the A3A-A3H genes, and found that A3G and A3F had the greatest anti-HIV-1 activity compared with that of other members. The results of this study indicate that A3G and A3F might play critical roles in limiting HIV-1 replication in NPMs in vivo. Furthermore, this research provides valuable information for the optimization of monkey models of HIV-1 infection.
Insights
Northern pig-tailed macaques (Macaca leonina) possess APOBEC3G and APOBEC3F, which significantly inhibit HIV-1 replication. These findings are crucial for developing better HIV-1 monkey models.
Area of Science:
- Virology
- Immunology
- Primatology
Background:
- Northern pig-tailed macaques (Macaca leonina) are susceptible to HIV-1 due to TRIM5α deficiency.
- Despite TRIM5α loss, persistent HIV-1 replication suggests other host restriction factors are present.
- The role of APOBEC3 proteins in restricting HIV-1 in Macaca leonina was previously unknown.
Purpose of the Study:
- To investigate the anti-HIV-1 activity of APOBEC3 proteins in Northern pig-tailed macaques.
- To identify specific APOBEC3 members that inhibit HIV-1 replication in this primate model.
Main Methods:
- Cloning of Northern pig-tailed macaque APOBEC3A-APOBEC3H genes.
- BLAST analysis to compare coding sequences with related macaque species.
- Assessment of anti-HIV-1 activities of cloned APOBEC3 genes.
Main Results:
- The coding sequences of NPM APOBEC3 genes showed 99% identity to those of rhesus and southern pig-tailed macaques.
- APOBEC3G and APOBEC3F exhibited the most potent anti-HIV-1 activity among the tested APOBEC3 members.
- Other APOBEC3 members demonstrated less significant inhibition of HIV-1 replication.
Conclusions:
- APOBEC3G and APOBEC3F likely play a significant role in limiting in vivo HIV-1 replication in Northern pig-tailed macaques.
- This study provides essential data for refining macaque models used in HIV-1 research.
- Understanding these host restriction factors can aid in the development of novel HIV-1 therapies.
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