title: The putative U94 integrase is dispensable for human herpesvirus 6 (HHV-6) chromosomal integration.
abstract: Human herpesvirus 6 (HHV-6) can integrate its genome into the telomeres of host chromosomes and is present in the germline of about 1 % of the human population. HHV-6 encodes a putative integrase U94 that possesses all molecular functions required for recombination including DNA-binding, ATPase, helicase and nuclease activity, and was hypothesized by many researchers to facilitate integration ever since the discovery of HHV-6 integration. However, analysis of U94 in the virus context has been hampered by the lack of reverse-genetic systems and efficient integration assays. Here, we addressed the role of U94 and the cellular recombinase Rad51 in HHV-6 integration. Surprisingly, we could demonstrate that HHV-6 efficiently integrated in the absence of U94 using a new quantitative integration assay. Additional inhibition of the cellular recombinase Rad51 had only a minor impact on virus integration. Our results shed light on this complex integration mechanism that includes factors beyond U94 and Rad51.
authors.affiliation: Institut für Virologie, Freie Universität Berlin, Robert von Ostertag-Straße 7-13, 14163 Berlin, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Wallaschek
authors.affiliation: Division of Infectious Disease and Immunity, CHU de Québec Research Center, Quebec city, Quebec G1V 4G2, Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: Gravel
authors.affiliation: Division of Infectious Disease and Immunity, CHU de Québec Research Center, Quebec city, Quebec G1V 4G2, Canada.|Department of Microbiology, Infectious Disease and Immunology, Faculty of Medicine, Université Laval, Quebec city, Québec, G1V 0A6, Canada.
authors.forename: Louis
authors.initials: L
authors.lastname: Flamand
authors.affiliation: Institut für Virologie, Freie Universität Berlin, Robert von Ostertag-Straße 7-13, 14163 Berlin, Germany.
authors.forename: Benedikt B
authors.initials: BB
authors.lastname: Kaufer
mesh_terms: D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D051135:Rad51 Recombinase / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D016662:Virus Integration
chemical_list: D004268:DNA-Binding Proteins; D014764:Viral Proteins; D019426:Integrases; C495153:RAD51 protein, human; D051135:Rad51 Recombinase