研究成果

ヒトウイルスのサル感染馴化メカニズムの解明

Development of a novel macaque-tropic HIV-1 adapted to cynomolgus macaques

22/10/16

Hirotaka Ode, Akatsuki Saito, Ayaka Washizaki, Yohei Seki, Takeshi Yoshida, Shigeyoshi Harada, Hiroshi Ishii, Tatsuo Shioda, Yasuhiro Yasutomi, Tetsuro Matano, Tomoyuki Miura, Hirofumi Akari, Yasumasa Iwatani Development of a novel macaque-tropic HIV-1 adapted to cynomolgus macaques  Journal of General Virology 103(10), 2022

We previously reported that a macaque-tropic HIV-1 efficiently replicates in peripheral blood mononuclear cells of cynomolgus macaques; However, the macaques infected with the HIV-1 displayed low viral loads during the acute phase with subsequent short-term viremia. These virological phenotypes in vivo differed from those observed in most HIV-1-infected humans.

In this study, we found that serial in vivo passages of a CCR5-tropic HIV-1mt, AS38 resulted in higher viral loads during the acute phase and prolonged periods of persistent viremia. Whole-genome sequencing in the in vivo-growing HIV-1 demonstrated that the emergence of a unique 15-nt deletion within the vif gene, which resulted in a significant increase in Vpr protein expression without affecting Vif-mediated function to antagonize antiretroviral host factors APOBEC3s. These results indicate that Vpr may play a critical role for HIV-1 replication in the macaques.

Hirotaka Ode, Akatsuki Saito, Ayaka Washizaki, Yohei Seki, Takeshi Yoshida, Shigeyoshi Harada, Hiroshi Ishii, Tatsuo Shioda, Yasuhiro Yasutomi, Tetsuro Matano, Tomoyuki Miura, Hirofumi Akari, Yasumasa Iwatani Development of a novel macaque-tropic HIV-1 adapted to cynomolgus macaques Journal of General Virology 103(10), 2022