Amino-terminal region of the human immunodeficiency virus type 1 nucleocapsid is required for human APOBEC3G packaging.
APOBEC3G exerts its antiviral activity by targeting to retroviral particles and inducing viral DNA hypermutations in the absence of Vif. However, the mechanism by which APOBEC3G is packaged into virions remains unclear. We now report that viral genomic RNA enhances but is not essential for human APOBEC3G packaging into human immunodeficiency virus type 1 (HIV-1) virions. Packaging of APOBEC3G was also detected in HIV-1 Gag virus-like particles (VLP) that lacked all the viral genomic RNA packaging signals. Human APOBEC3G could be packaged efficiently into a divergent subtype HIV-1, as well as simian immunodeficiency virus, strain mac, and murine leukemia virus Gag VLP. Cosedimentation of human APOBEC3G and intracellular Gag complexes was detected by equilibrium density and velocity sucrose gradient analysis. Interaction between human APOBEC3G and HIV-1 Gag was also detected by coimmunoprecipitation experiments. This interaction did not require p6, p1, or the C-terminal region of NCp7. However, the N-terminal region, especially the first 11 amino acids, of HIV-1 NCp7 was critical for HIV-1 Gag and APOBEC3G interaction and virion packaging. The linker region flanked by the two active sites of human APOBEC3G was also important for efficient packaging into HIV-1 Gag VLP. Association of human APOBEC3G with RNA-containing intracellular complexes was observed. These results suggest that the N-terminal region of HIV-1 NC, which is critical for binding to RNA and mediating Gag-Gag oligomerization, plays an important role in APOBEC3G binding and virion packaging.
Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205, USA.
Kun
K
Luo
Bindong
B
Liu
Zuoxiang
Z
Xiao
Yunkai
Y
Yu
Xianghui
X
Yu
Robert
R
Gorelick
Xiao-Fang
XF
Yu
D000071480:APOBEC-3G Deaminase; D000595:Amino Acid Sequence; D003564:Cytidine Deaminase; D015685:Fusion Proteins, gag-pol / Q000502:physiology; D015683:Gene Products, gag / Q000502:physiology; D015497:HIV-1 / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D019251:Nucleocapsid / Q000737:chemistry* / Q000502:physiology; D009700:Nucleoside Deaminases; D011506:Proteins / Q000502:physiology*; D012097:Repressor Proteins; D014771:Virion / Q000502:physiology; D019065:Virus Assembly
D015685:Fusion Proteins, gag-pol; D015683:Gene Products, gag; D011506:Proteins; D012097:Repressor Proteins; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase