Host Restriction Factors APOBEC3G/3F and Other Interferon-Related Gene Expressions Affect Early HIV-1 Infection in Northern Pig-Tailed Macaque (Macaca leonina).

Abstract

The northern pig-tailed macaques (NPMs) lack TRIM5α, an antiviral restriction factor, and instead have TRIM5-CypA. In our previous study, we demonstrated that HIV-1NL4-3 successfully infected NPMs and formed a long-term viral reservoir in vivo. However, the HIV-1-infected NPMs showed relatively high viremia in the first 6 weeks of infection, which declined thereafter suggesting that HIV-1 NL4-3 infection in these animals was only partly permissive. To optimize HIV-1 infection in NPMs therefore, we generated HIV-1NL4-R3A and stHIV-1sv, and infected NPMs with these viruses. HIV-1NL4-R3A and stHIV-1sv can replicate persistently in NPMs during 41 weeks of acute infection stage. Compared to the HIV-1NL4-R3A, stHIV-1sv showed a notably higher level of replication, and the NPMs infected with the latter induced a more robust neutralizing antibody but a weaker cellular immune response. In addition, IFN-I signaling was significantly up-regulated with the viral replication, and was higher in the stHIV-1sv infected macaques. Consequently, the sequences of pro-viral env showed fewer G-A hyper-mutations in stHIV-1sv, suggesting that vif gene of SIV could antagonize the antiviral effects of APOBEC3 proteins in NPMs. Taken together, NPMs infected with HIV-1NL4-R3A and stHIV-1sv show distinct virological and immunological features. Furthermore, interferon-related gene expression might play a role in controlling primary HIV-1NL4-R3A and stHIV-1sv replication in NPMs. This result suggests NPM is a potential HIV/AIDS animal model.

• Authors: Wei Pang, Jia-Hao Song, Ying Lu, Xiao-Liang Zhang, Hong-Yi Zheng, Jin Jiang, Yong-Tang Zheng
• Journal: Frontiers in immunology (Front Immunol) Vol. 9 Pg. 1965 ( 2018) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 30210504 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Restriction Factors
• Carrier Proteins
• Interferon Type I
• Tripartite Motif Proteins
• TRIM5 protein, human
• Ubiquitin-Protein Ligases
• APOBEC-3G Deaminase

Topics

• APOBEC-3G Deaminase (genetics, metabolism)
• Animals
• Antiviral Restriction Factors
• Carrier Proteins (genetics, metabolism)
• Disease Models, Animal
• Female
• Gene Expression
• Genes, vif (genetics)
• HIV Infections (immunology)
• HIV-1 (physiology)
• Humans
• Interferon Type I (genetics, metabolism)
• Macaca
• Male
• Mutation (genetics)
• Simian Acquired Immunodeficiency Syndrome (immunology)
• Simian Immunodeficiency Virus (physiology)
• Tripartite Motif Proteins
• Ubiquitin-Protein Ligases
• Viremia
• Virus Replication