Deaminase-Independent Inhibition of Parvoviruses by the APOBEC3A Cytidine Deaminase

PLoS Pathogens

Nathaniel R. Landau¹  Yoshiyuki Hakata¹  Eric Logue¹  David J. Pintel²  Daniel C. Linfesty³  Iñigo Narvaiza³  Benjamin N. Greener³  Matthew D. Weitzman³ 

[1] Department of Microbiology, New York University School of Medicine, New York, New York, United States of America;Department of Molecular Microbiology and Immunology, University of Missouri–Columbia, School of Medicine, Life Sciences Center, Columbia, Missouri, United States of America;Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California, United States of America

关键词: DNA replication;    Viral replication;    Immunoblotting;    293T cells;    Parvoviruses;    Immune system proteins;    Plasmid construction;    Transfection;   

DOI  :  10.1371/journal.ppat.1000439

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 of both wild-type AAV and the autonomous parvovirus minute virus of mice (MVM). In addition, we identify specific residues of A3A that confer activity against AAV when substituted into A3G. In summary, our results demonstrate that deaminase activity is not necessary for the antiviral activity of A3A against parvoviruses.

【 授权许可】

CC BY