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.

Animal Models in the Evaluation of the Effectiveness of Phage Therapy for Infections Caused by Gram-Negative Bacteria from the ESKAPE Group and the Reliability of Its Use in Humans

“…The ethical reports highlight many of the related problems, including the stressful conditions during the transport of monkeys from their natural environment, and propose replacement variants, such as specially designed cells expressing human proteins that are implanted into smaller animals, such as rodents [76]. Despite this, valuable knowledge on many diseases that threaten humans has been gained through research with macaques, including studies of the immune system during HIV infection/AIDS progression [77,78], and in conjunction with HIV vaccine research [79], as well as through learning the details of the immune response in tuberculosis [80]. Another major problem faced in planning research on vertebrate animals is the inevitability of obtaining approval from an ethics committee to work with animals.…”

Northern pig-tailed macaques (<i>Macaca leonina</i>) infected with SARS-CoV-2 show rapid viral clearance and persistent immune response

“…However, only mild clinical manifestations and temporary cytokine increases have been observed in RMs ( Munster et al, 2020 ; Song et al, 2020 ). Previously, we confirmed that northern pig-tailed macaques ( Macaca leonina , NPMs) are a suitable animal model for acquired immune deficiency syndrome (AIDS) research ( Pang et al, 2018 ; Zhang et al, 2018 ). Different from RMs, NPMs can be infected with HIV-1 and viral reservoirs can form in vivo ( Pang et al, 2017 ).…”

CXCR4- and CCR5-Tropic HIV-1 Clones Are Both Tractable to Grow in Rhesus Macaques

“…This is the first report to demonstrate the capability of CXCR4-tropic and CCR5-tropic HIV-1 derivative viruses to grow in rhesus macaques. Thus far, pig-tailed and cynomolgus macaques have been the only NHPs to perform in vivo infection studies on HIV-1/AIDS using viruses genetically recognizable as HIV-1 ( Igarashi et al, 2007 ; Hatziioannou et al, 2009 , 2014 ; Saito et al, 2011 , 2013 ; Thippeshappa et al, 2011 ; Otsuki et al, 2014 ; Peng et al, 2018 ). The rhesus macaque is by far the best suited NHP species for HIV-1 model studies from various points of views as described above.…”