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ABSTRACT: The human APOBEC3 family consists of seven deaminases (A3A to A3H), some of which display potent antiretroviral activity against HIV-1 and other retroviruses. Studies that analyzed the effect of A3G on Human T-lymphotropic virus type 1 (HTLV-1) infectivity resulted in conflicting findings and our knowledge on HTLV-1 restriction by other A3 proteins remains limited. Since HTLV-1 targets CD4+ T-cells, much like HIV, we hypothesized that A3 proteins, other than A3G, restrict HTLV-1. All seven human A3 proteins were tested in HTLV-1 reporter and HIV-1 infectivity assays. We show that A3A, A3B and A3H haplotype 2 acted as potent inhibitors of HTLV-1. Wild-type HIV-1, however, was restricted by A3B and A3H hapII, but not by A3A. Catalytic site mutants of A3A, A3B and A3H hapII showed that A3A and A3B restriction of HTLV-1 required deaminase activity. However, A3H hapII acted in a deaminase-independent manner when restricting HTLV-1, while requiring deaminase activity for HIV-1 restriction. We also analyzed A3 editing of HTLV-1 in five T-cell lines obtained from HTLV-1 infected patients. These cell lines contained extensively edited HTLV-1 sequences with G-to-A mutations in dinucleotide contexts suggestive of A3G and other A3 enzyme activities. Comparison of the A3 induced mutations from reporter cells and the patient derived cell lines indicate that A3G but also other A3 members, possibly A3A and A3B, affect HTLV-1 in vivo. Taken together, our data indicates that HTLV-1 is a likely target for multiple A3 proteins.
Journal of Virology 03/2012; · 5.40 Impact Factor
