APOBEC3G and APOBEC3F require an endogenous cofactor to block HIV-1 replication.
APOBEC3G (A3G)/APOBEC3F (A3F) are two members of APOBEC3 cytidine deaminase subfamily. Although they potently inhibit the replication of vif-deficient HIV-1, this mechanism is still poorly understood. Initially, A3G/A3F were thought to catalyze C-to-U transitions on the minus-strand viral cDNAs during reverse transcription to disrupt the viral life cycle. Recently, it was found more likely that A3G/A3F directly interrupts viral reverse transcription or integration. In addition, A3G/A3F are both found in the high-molecular-mass complex in immortalized cell lines, where they interact with a number of different cellular proteins. However, there has been no evidence to prove that these interactions are required for A3G/A3F function. Here, we studied A3G/A3F-restricted HIV-1 replication in six different human T cell lines by infecting them with wild-type or vif-deficient HIV-1. Interestingly, in a CEM-derived cell line CEM-T4, which expresses high levels of A3G/A3F proteins, the vif-deficient virus replicated as equally well as the wild-type virus, suggesting that these endogenous antiretroviral genes lost anti-HIV activities. It was confirmed that these A3G/A3F genes do not contain any mutation and are functionally normal. Consistently, overexpression of exogenous A3G/A3F in CEM-T4 cells still failed to restore their anti-HIV activities. However, this activity could be restored if CEM-T4 cells were fused to 293T cells to form heterokaryons. These results demonstrate that CEM-T4 cells lack a cellular cofactor, which is critical for A3G/A3F anti-HIV activity. We propose that a further study of this novel factor will provide another strategy for a complete understanding of the A3G/A3F antiretroviral mechanism.
Han
Yanxing
Y
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, United States of America.
Wang
Xiaojun
X
Dang
Ying
Y
Zheng
Yong-Hui
YH
D000071480:APOBEC-3G Deaminase; D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D003564:Cytidine Deaminase / Q000378:metabolism*; D043525:Cytosine Deaminase / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011817:Rabbits; D012097:Repressor Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D014779:Virus Replication / Q000502:physiology*; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase