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.
Highlights
Non-human primates (NHPs) are the preferred experimental animals for HIV-1/AIDS research
We investigated the early virological, humoral and cellular immune responses, and the interferon-related gene expression profiles in northern pig-tailed macaques (NPMs) following HIV-1NL4−R3A and stHIV-1sv infection
NPMs can permit HIV-1NL4−R3A and stHIV-1sv persistently replicate 41 weeks in the observing times of acute infection stage, with only modest fluctuations but no obvious decrease of main immune cells during the primary infection of both viruses, indicating that HIV-1NL4−R3A and stHIV-1sv infection were partly inhibited by the host immune system
Summary
Non-human primates (NHPs) are the preferred experimental animals for HIV-1/AIDS research. Previous studies have reported that most macaques can be infected by SIV, of which the rhesus macaque (Macaca mulatta), cynomolgus macaque (Macaca fascularis) and pig-tailed macaque (Macaca nemestrina) are widely used as the animal models of AIDS [1]. Pig-tailed macaques can be infected with HIV-1, as they lack the HIV-1 blocking protein TRIM5α [3,4,5,6,7]. Based on their geographical distribution and morphology differences, pig-tailed macaques are divided into three species: sunda pig-tailed macaque (M. nemestrina), northern pig-tailed macaque (M. leonina), and mentawai macaque (M. pagensis) [8]. The sunda pig-tailed macaques (SPMs) are the most frequently used species for HIV-1 infection [9,10,11,12,13,14,15,16,17,18]
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