title: APOBEC4 Enhances the Replication of HIV-1.
abstract: APOBEC4 (A4) is a member of the AID/APOBEC family of cytidine deaminases. In this study we found a high mRNA expression of A4 in human testis. In contrast, there were only low levels of A4 mRNA detectable in 293T, HeLa, Jurkat or A3.01 cells. Ectopic expression of A4 in HeLa cells resulted in mostly cytoplasmic localization of the protein. To test whether A4 has antiviral activity similar to that of proteins of the APOBEC3 (A3) subfamily, A4 was co-expressed in 293T cells with wild type HIV-1 and HIV-1 luciferase reporter viruses. We found that A4 did not inhibit the replication of HIV-1 but instead enhanced the production of HIV-1 in a dose-dependent manner and seemed to act on the viral LTR. A4 did not show detectable cytidine deamination activity in vitro and weakly interacted with single-stranded DNA. The presence of A4 in virus producer cells enhanced HIV-1 replication by transiently transfected A4 or stably expressed A4 in HIV-susceptible cells. APOBEC4 was capable of similarly enhancing transcription from a broad spectrum of promoters, regardless of whether they were viral or mammalian. We hypothesize that A4 may have a natural role in modulating host promoters or endogenous LTR promoters.
authors.affiliation: Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.|Division of Medical Biotechnology, Paul-Ehrlich-Institute, Langen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Marino
authors.affiliation: Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.|Division of Medical Biotechnology, Paul-Ehrlich-Institute, Langen, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Perković
authors.affiliation: Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Hain
authors.affiliation: Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors.forename: Ananda A
authors.initials: AA
authors.lastname: Jaguva Vasudevan
authors.affiliation: Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.|Division of Medical Biotechnology, Paul-Ehrlich-Institute, Langen, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Hofmann
authors.affiliation: Biostatistics, Paul-Ehrlich-Institute, Langen, Germany.
authors.forename: Kay-Martin
authors.initials: KM
authors.lastname: Hanschmann
authors.affiliation: Division of Medical Biotechnology, Paul-Ehrlich-Institute, Langen, Germany.|Product Testing of Immunological Medicinal Products for Veterinary Uses, Paul-Ehrlich-Institute, Langen, Germany.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Mühlebach
authors.affiliation: Division of Medical Biotechnology, Paul-Ehrlich-Institute, Langen, Germany.
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Schumann
authors.affiliation: Host-Pathogen Interactions, Paul-Ehrlich-Institute, Langen, Germany.|Sanford Burnham Prebys Medical Discovery Institute, Immunity and Pathogenesis Program, La Jolla, California, United States of America.
authors.forename: Renate
authors.initials: R
authors.lastname: König
authors.affiliation: Division of Medical Biotechnology, Paul-Ehrlich-Institute, Langen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Cichutek
authors.affiliation: Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.affiliation: Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.|Division of Medical Biotechnology, Paul-Ehrlich-Institute, Langen, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Münk
mesh_terms: D002460:Cell Line; D003562:Cytidine / Q000378:metabolism; D003564:Cytidine Deaminase / Q000378:metabolism / Q000502:physiology*; D003641:Deamination; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D013737:Testis / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
chemical_list: D003562:Cytidine; C510823:APOBEC4 protein, human; D003564:Cytidine Deaminase