HIV-1 can infect northern pig-tailed macaques (Macaca leonina) and form viral reservoirs in vivo

Abstract

Viral reservoirs of HIV-1 are a major obstacle for curing AIDS. The novel animal models that can be directly infected with HIV-1 will contribute to develop effective strategies for eradicating infections. Here, we inoculated 4 northern pig-tailed macaques (NPM) with the HIV-1 strain HIV-1 NL4.3 and monitored the infection for approximately 3 years (150 weeks). The HIV-1-infected NPMs showed transient viremia for about 10 weeks after infection. However, cell-associated proviral DNA and viral RNA persisted in the peripheral blood and lymphoid organs for about 3 years. Moreover, replication-competent HIV-1 could be successfully recovered from peripheral blood mononuclear cells (PBMCs) during long-term infection. The numbers of resting CD4 + T cells in HIV-1 infected NPMs harboring proviruses fell within a range of 2-to 3-log 10 per million cells, and these proviruses could be reactivated both ex vivo and in vivo in response to co-stimulation with the latency-reversing agents JQ1 and prostratin. Our results suggested that NPMs can be infected with HIV-1 and a long-term viral reservoir was formed in NPMs, which might serve as a potential model for HIV-1 reservoir research.

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

“…The viral load was quantified by a real-time PCR method based on amplification of a HIV-1 NL4.3 -derived Gag coding sequence as described previously (22). …”

“…The plasma viral RNA was extracted by high pure viral RNA Kit (Roche) according to the manufacturer's instructions. The viral load was quantified by a real-time PCR method based on amplification of a HIV-1 NL4.3 -derived Gag coding sequence as described previously ( 22 ).…”

“…Total cellular DNA was extracted using the QIAmp DNA Blood Mini Kit (Qiagen, German) and eluted in 100 μl. HIV-1 DNA and RNA was quantified by qPCR as previously reported ( 22 ).…”

“…Furthermore, replication-competent HIV-1 could be successfully reactivated both ex vivo and in vivo in response to co-stimulation with the latency-reversing agents JQ1 and prostratin. These results suggest HIV-1 can replicate at a low level and form a long term viral reservoir in NPMs ( 22 ), making them a potential animal model for HIV/AIDS research.…”

寄生虫逃避免疫功能不全宿主

“…Non-human primates (NHPs) are crucial animal models for understanding the pathogenesis of HIV infection ( Karlsson et al, 1997 ; Letvin, 1992 ). Simian immunodeficiency virus (SIV) infections in rhesus macaques and northern pig-tailed macaques (NPMs) result in an immunocompromised and AIDS-like disease similar to that seen in HIV patients, as established in our laboratory ( Pang et al, 2017 ; Zhang et al, 2017a , b ). In this study, NPMs with different parasitic loads after infection with SIVmac239 were used to detect immunological and pathological differences to reveal the relationship between viral infection and parasites.…”