reduced apobec3h variant anti-viral activities are associated with altered rna binding activities减少apobec3h变体抗病毒活动与改变rna绑定相关联的活动.pdfVIP

Reduced APOBEC3H Variant Anti-Viral Activities Are Associated with Altered RNA Binding Activities 1 2 1,2 3 1,2 Anjie Zhen , Juan Du , Xiaohong Zhou , Yong Xiong , Xiao-Fang Yu * 1 Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America, 2 First Affiliated Hospital, Jilin University, Jilin, China, 3 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, United States of America Abstract APOBEC3H (A3H) is a member of the APOBEC3 family of proteins with varying activities against retroviruses and retrotransposons. The A3H gene contains several single nucleotide polymorphisms and up to seven haplotypes have been detected in humans. Although variations in anti-viral function among A3H haplotypes are not fully understood, only 15N105R-containing A3H variants are known to have potent activities against Vif-deficient HIV-1. Unique motif RLYY(F/Y)W of APOBEC3G (A3G) and APOBEC3F (A3F) required for 7SL RNA binding and HIV-1 incorporation is also conserved in all A3H variants. Like A3G, A3H HapII also demonstrated high binding affinity to host small RNAs such as 7SL and Y RNAs. Mutation of a critical amino acid, W115A resulted in reduced expression level, decreased affinity for 7SL RNA, impairment of virion packaging and reduced anti-viral activity. By comparison, A3H HapI had lower binding affinities to host small RNAs and reduced efficiency of virion incorporation, resulting in significantly reduced anti-viral activity. The SNP DN15 commonly found in A3H HapIII and HapIV abolished their abilities to associate with RNAs, and A3H HapIID15N failed to