Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
Institute of Health Sciences, Anhui University, Hefei, China.
Front Immunol. 2018 Aug 28;9:1965. doi: 10.3389/fimmu.2018.01965. eCollection 2018.
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-1 successfully infected NPMs and formed a long-term viral reservoir . However, the HIV-1-infected NPMs showed relatively high viremia in the first 6 weeks of infection, which declined thereafter suggesting that HIV-1 infection in these animals was only partly permissive. To optimize HIV-1 infection in NPMs therefore, we generated HIV-1 and stHIV-1sv, and infected NPMs with these viruses. HIV-1 and stHIV-1sv can replicate persistently in NPMs during 41 weeks of acute infection stage. Compared to the HIV-1, 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 showed fewer G-A hyper-mutations in stHIV-1sv, suggesting that gene of SIV could antagonize the antiviral effects of APOBEC3 proteins in NPMs. Taken together, NPMs infected with HIV-1 and stHIV-1sv show distinct virological and immunological features. Furthermore, interferon-related gene expression might play a role in controlling primary HIV-1 and stHIV-1sv replication in NPMs. This result suggests NPM is a potential HIV/AIDS animal model.
北方猪尾猕猴(NPMs)缺乏抗病毒限制因子 TRIM5α,而是具有 TRIM5-CypA。在我们之前的研究中,我们证明了 HIV-1 成功感染了 NPMs 并形成了长期的病毒储存库。然而,HIV-1 感染的 NPMs 在感染的前 6 周内表现出相对较高的病毒血症,此后病毒血症下降,这表明这些动物中的 HIV-1 感染只是部分许可的。为了优化 NPMs 中的 HIV-1 感染,我们生成了 HIV-1 和 stHIV-1sv,并将这些病毒感染了 NPMs。在急性感染阶段的 41 周内,HIV-1 和 stHIV-1sv 可以在 NPMs 中持续复制。与 HIV-1 相比,stHIV-1sv 的复制水平明显更高,感染后者的 NPMs 诱导出更强的中和抗体,但较弱的细胞免疫反应。此外,IFN-I 信号通路随着病毒的复制而显著上调,在感染 stHIV-1sv 的猕猴中更高。因此,在 stHIV-1sv 中,前病毒的序列显示出较少的 G-A 超突变,这表明 SIV 的基因可能在 NPMs 中拮抗 APOBEC3 蛋白的抗病毒作用。总之,感染 HIV-1 和 stHIV-1sv 的 NPMs 表现出不同的病毒学和免疫学特征。此外,干扰素相关基因的表达可能在控制 NPMs 中 HIV-1 和 stHIV-1sv 的原发性复制中发挥作用。这一结果表明 NPM 是一种潜在的 HIV/AIDS 动物模型。