Cytidine deaminases APOBEC3G and APOBEC3F interact with human immunodeficiency virus type 1 integrase and inhibit proviral DNA formation.
APOBEC3G (A3G) is a single-stranded DNA cytidine deaminase that targets retroviral minus-strand DNA and has potent antiviral activity against diverse retroviruses. However, the mechanisms of A3G antiviral functions are incompletely understood. Here we demonstrate that A3G, A3F, and, to a lesser extent, the noncatalytic A3GC291S block human immunodeficiency virus type 1 (HIV-1) replication by interfering with proviral DNA formation. In HIV-1 virions, A3G interacted with HIV-1 integrase and nucleocapsid, key viral factors for reverse transcription and integration. Unlike A3G, the weak antiviral A3C cytidine deaminase did not interact with either of these factors and did not affect viral reverse transcription or proviral DNA formation. Thus, multiple steps of the HIV-1 replication cycle, most noticeably the formation of proviral DNA, are inhibited by both cytidine deamination-dependent and -independent mechanisms.
Luo
Kun
K
Department of Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
Wang
Tao
T
Liu
Bindong
B
Tian
Chunjuan
C
Xiao
Zuoxiang
Z
Kappes
John
J
Yu
Xiao-Fang
XF
D000071480:APOBEC-3G Deaminase; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000378:metabolism*; D004279:DNA, Viral; D019427:HIV Integrase / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009700:Nucleoside Deaminases / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D048348:Reverse Transcription / Q000502:physiology; D016662:Virus Integration / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*
D004279:DNA, Viral; D012097:Repressor Proteins; D019427:HIV Integrase; D009700:Nucleoside Deaminases; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase