deaminase-independent inhibition of parvoviruses by the apobec3a cytidine deaminasedeaminase-independent细小病毒的抑制apobec3a胞嘧啶核苷脱氨酶.pdf

Deaminase-Independent Inhibition of Parvoviruses by the APOBEC3A Cytidine Deaminase ˜ 1 1 1¤ 2 3 Inigo Narvaiza , Daniel C. Linfesty , Benjamin N. Greener , Yoshiyuki Hakata , David J. Pintel , Eric 2 2 1 Logue , Nathaniel R. Landau , Matthew D. Weitzman * 1 Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California, United States of America, 2 Department of Microbiology, New York University School of Medicine, New York, New York, United States of America, 3 Department of Molecular Microbiology and Immunology, University of Missouri–Columbia, School of Medicine, Life Sciences Center, Columbia, Missouri, United States of America Abstract The APOBEC3 proteins form a multigene family of cytidine deaminases with inhibitory activity against viruses and retrotransposons. In contrast to APOBEC3G (A3G), APOBEC3A (A3A) has no effect on lentiviruses but dramatically inhibits replication of the parvovirus adeno-associated virus (AAV). To study the contribution of deaminase activity to the antiviral activity of A3A, we performed a comprehensive mutational analysis of A3A. By mutation of non-conserved residues, we found that regions outside of the catalytic active site contribute to both deaminase and antiviral activities. Using A3A point mutants and A3A/A3G chimeras, we show that deaminase activity is not required for inhibition of recombinant AAV production. We also found that deaminase-deficient A3A mutants block replication