title: APOBEC3A, APOBEC3B, and APOBEC3H haplotype 2 restrict human T-lymphotropic virus type 1.
abstract: The human APOBEC3 family consists of seven cytidine 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 of HTLV-1 restriction by other A3 proteins remains limited. Since HTLV-1, much like HIV, targets CD4(+) T cells, 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 (A3H hapII) acted as potent inhibitors of HTLV-1. Wild-type HIV-1, in contrast, 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 APOBEC3 mutagenesis. 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 indicate that HTLV-1 is a likely target for multiple A3 proteins.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Marcel
authors.initials: M
authors.lastname: Ooms
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Krikoni
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Kress
authors.forename: Viviana
authors.initials: V
authors.lastname: Simon
authors.forename: Carsten
authors.initials: C
authors.lastname: Münk
mesh_terms: D000619:Aminohydrolases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020134:Catalytic Domain; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology; D006239:Haplotypes; D015368:Human T-lymphotropic virus 1 / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D015778:Minor Histocompatibility Antigens; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D015778:Minor Histocompatibility Antigens; D050505:Mutant Proteins; D011506:Proteins; C529313:APOBEC3H protein, human; D000619:Aminohydrolases; C121399:APOBEC3A protein, human; C495794:APOBEC3B protein, human; D003564:Cytidine Deaminase