The incorporation of APOBEC3 proteins into murine leukemia viruses.
APOBEC3 proteins represent a group of potent intrinsic inhibitors of retroviral replication. Murine APOBEC3 (mA3) is able to inhibit HIV-1, whereas it is inactive against Moloney murine leukemia virus (MLV). In this work, we present evidence showing that mA3, compared to hA3G, is incorporated inefficiently into MLV, while the abilities of mA3 and hA3G to be packaged into HIV-1 are similar. The nucleocapsid (NC) domain of HIV-1 is capable of facilitating the interaction of mA3 with HIV-1 Gag, and thereby the incorporation of mA3 into HIV-1. Swapping studies of the NC domains in HIV-1 and MLV indicate that MLV NC domain is responsible for viral exclusion of mA3, due to its inability to facilitate the mA3/Gag interaction. The interaction between mA3 and HIV-1 Gag is mediated by the linker region between two zinc coordination motifs in mA3, similar to what has been found for the incorporation of hA3G into both HIV-1 and MLV. These results suggest that the interaction between NC domains and the linker regions might represent a common mechanism for viral incorporation of APOBEC3 proteins, and the inefficient incorporation of endogenous mA3 appears to be a strategy by which MLV escapes the inhibitory effect of mA3.
Zhang
Li
L
Department of Virology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing 100050, China.
Li
Xiaoyu
X
Ma
Jing
J
Yu
Liyan
L
Jiang
Jiandong
J
Cen
Shan
S
D000071480:APOBEC-3G Deaminase; D000818:Animals; D002460:Cell Line; D003564:Cytidine Deaminase / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D051379:Mice; D008979:Moloney murine leukemia virus / Q000378:metabolism / Q000472:pathogenicity*; D041681:NIH 3T3 Cells; D019251:Nucleocapsid / Q000737:chemistry / Q000378:metabolism*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
D054301:gag Gene Products, Human Immunodeficiency Virus; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; C503504:Apobec3 protein, mouse; D003564:Cytidine Deaminase