Distinct viral determinants for the packaging of human cytidine deaminases APOBEC3G and APOBEC3C.
Human APOBEC3G and other APOBEC3 cytidine deaminases inhibit a variety of retroviruses, including Vif-deficient HIV-1. These host proteins are packaged into viral particles and inhibit the replication of virus in new target cells. A3G and A3F are known to be efficiently packaged into HIV-1 virions by binding to 7SL RNA through the Gag NC domain; however, the packaging mechanisms of other APOBEC3 proteins are poorly defined. We have now demonstrated that APOBEC3C (A3C) can be efficiently packaged into HIV-1 virions that are deficient for viral genomic RNA. Inhibition of the encapsidation of 7SL RNA into HIV-1 virions blocked the packaging of A3G, but not A3C. While the NC domain is required for efficient packaging of A3G, deletion of this domain had little effect on A3C packaging into HIV-1 Gag particles. A3C interacted with HIV-1 Gag which was MA domain-dependent and RNA-dependent. Deletion of the MA domain of HIV-1 Gag inhibited A3C but not A3G packaging into HIV-1 Gag particles. Thus, A3G and A3C have evolved to use distinct mechanisms for targeting retroviruses.
Wang
Tao
T
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Zhang
Wenyan
W
Tian
Chunjuan
C
Liu
Bindong
B
Yu
Yunkai
Y
Ding
Lingmei
L
Spearman
Paul
P
Yu
Xiao-Fang
XF
D000071480:APOBEC-3G Deaminase; D001483:Base Sequence; D002460:Cell Line; D003564:Cytidine Deaminase / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D015750:Genes, gag; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011485:Protein Binding; D012367:RNA, Viral / Q000235:genetics; D017384:Sequence Deletion; D019065:Virus Assembly / Q000235:genetics / Q000502:physiology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000502:physiology
D017931:DNA Primers; D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus; D000071480:APOBEC-3G Deaminase; C495795:APOBEC3C protein, human; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase