the restriction of zoonotic perv transmission by human apobec3g人类apobec3g传播人畜共患恋物癖的限制.pdfVIP

The Restriction of Zoonotic PERV Transmission by Human APOBEC3G ´ ´ 1,2,3,4. 1,2,3. 1,2,3 3,5 ´ ´ 4 1,2,3 Stefan R. Jonsson , Rebecca S. LaRue , Mark D. Stenglein , Scott C. Fahrenkrug , Valgerdur Andresdottir , Reuben S. Harris * 1 Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, United States of America, 2 Institute for Molecular Virology, University of Minnesota, Minneapolis, Minnesota, United States of America, 3 Arnold and Mabel Beckman Center for Transposon Research, University of Minnesota, Minneapolis, Minnesota, United States of America, 4 Institute for Experimental Pathology, University of ´ Iceland, Reykjavık, Iceland, 5 Department of Animal Sciences, University of Minnesota, St. Paul, Minnesota, United States of America The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus-producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over-expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with