A role for gorilla APOBEC3G in shaping lentivirus evolution including transmission to humans

Nakano, Yusuke; Yamamoto, Keisuke; Ueda, Mahoko Takahashi; Soper, Andrew; Konno, Yoriyuki; Kimura, Izumi; Uriu, Keiya; Kumata, Ryuichi; Aso, Hirofumi; Misawa, Naoko; Nagaoka, Shumpei; Shimizu, Soma; Mitsumune, Keito; Kosugi, Yusuke; Juarez-Fernandez, Guillermo; Ito, Jumpei; Nakagawa, So; Ikeda, Terumasa; Koyanagi, Yoshio; Harris, Reuben S.; Sato, Kei

The APOBEC3 deaminases are potent inhibitors of virus replication and barriers to cross-species transmission. For simian immunodeficiency virus (SIV) to transmit to a new primate host, as happened multiple times to seed the ongoing HIV-1 epidemic, the viral infectivity factor (Vif) must be capable of neutralizing the APOBEC3 enzymes of the new host. Although much is known about current interactions of HIV-1 Vif and human APOBEC3s, the evolutionary changes in SIV Vif required for transmission from chimpanzees to gorillas and ultimately to humans are poorly understood. Here, we demonstrate that gorilla APOBEC3G is a factor with the potential to hamper SIV transmission from chimpanzees to gorillas. Gain-of-function experiments using SIVcpzPtt Vif revealed that this barrier could be overcome by a single Vif acidic amino acid substitution (M16E). Moreover, degradation of gorilla APOBEC3F is induced by Vif through a mechanism that is distinct from that of human APOBEC3F. Thus, our findings identify virus adaptations in gorillas that preceded and may have facilitated transmission to humans.