TY - JOUR
T1 - Evolutionarily conserved pressure for the existence of distinct g2/m cell cycle arrest and a3h inactivation functions in hiv-1 vif
AU - Zhao, Ke
AU - Du, Juan
AU - Rui, Yajuan
AU - Zheng, Wenwen
AU - Kang, Jian
AU - Hou, Jingwei
AU - Wang, Kang
AU - Zhang, Wenyan
AU - Simon, Viviana A.
AU - Yu, Xiao Fang
N1 - Publisher Copyright:
© 2015 Taylor & Francis Group, LLC
PY - 2015/3/15
Y1 - 2015/3/15
N2 - HIV-1 Vif assembles the Cul5-EloB/C E3 ubiquitin ligase to induce proteasomal degradation of the cellular antiviral APOBEC3 proteins. Detailed structural studies have confirmed critical functional domains in Vif that we have previously identified as important for the interaction of EloB/C, Cul5, and CBFb. However, the mechanism by which Vif recognizes substrates remains poorly understood. Specific regions of Vif have been identified as being responsible for binding and depleting APOBEC3G and APOBEC3F. Interestingly, we have now identified distinct yet overlapping domains that are required for HIV-1 Vif-mediated G2/M-phase cell cycle arrest and APOBEC3H degradation, but not for the inactivation of APOBEC3G or APOBEC3F. Surprisingly, Vif molecules from primary HIV-1 variants that caused G2/M arrest were unable to inactivate APOBEC3H; on the other hand, HIV-1 Vif variants that could inactivate APOBEC3H were unable to induce G2/M arrest. All of these Vif variants still maintained the ability to inactivate APOBEC3G/F. Thus, primary HIV-1 variants have evolved to possess distinct functional activities that allow them to suppress APOBEC3H or cause G2 cell cycle arrest, using mutually exclusive interface domains. APOBEC3H depletion and G2 arrest are apparently evolutionary selected features that cannot co-exist on a single Vif molecule. The existence and persistence of both types of HIV-1 Vif variant suggests the importance of APOBEC3H suppression and cell cycle regulation for HIV-1’s survival in vivo.
AB - HIV-1 Vif assembles the Cul5-EloB/C E3 ubiquitin ligase to induce proteasomal degradation of the cellular antiviral APOBEC3 proteins. Detailed structural studies have confirmed critical functional domains in Vif that we have previously identified as important for the interaction of EloB/C, Cul5, and CBFb. However, the mechanism by which Vif recognizes substrates remains poorly understood. Specific regions of Vif have been identified as being responsible for binding and depleting APOBEC3G and APOBEC3F. Interestingly, we have now identified distinct yet overlapping domains that are required for HIV-1 Vif-mediated G2/M-phase cell cycle arrest and APOBEC3H degradation, but not for the inactivation of APOBEC3G or APOBEC3F. Surprisingly, Vif molecules from primary HIV-1 variants that caused G2/M arrest were unable to inactivate APOBEC3H; on the other hand, HIV-1 Vif variants that could inactivate APOBEC3H were unable to induce G2/M arrest. All of these Vif variants still maintained the ability to inactivate APOBEC3G/F. Thus, primary HIV-1 variants have evolved to possess distinct functional activities that allow them to suppress APOBEC3H or cause G2 cell cycle arrest, using mutually exclusive interface domains. APOBEC3H depletion and G2 arrest are apparently evolutionary selected features that cannot co-exist on a single Vif molecule. The existence and persistence of both types of HIV-1 Vif variant suggests the importance of APOBEC3H suppression and cell cycle regulation for HIV-1’s survival in vivo.
KW - Apobec3h
KW - Cell cycle regulation
KW - Evolutionary selection
KW - Proteasomal degradation
KW - Vif
UR - http://www.scopus.com/inward/record.url?scp=84928137477&partnerID=8YFLogxK
U2 - 10.1080/15384101.2014.1000212
DO - 10.1080/15384101.2014.1000212
M3 - Article
C2 - 25590520
AN - SCOPUS:84928137477
SN - 1538-4101
VL - 14
SP - 838
EP - 847
JO - Cell Cycle
JF - Cell Cycle
IS - 6
ER -