title: Molecular basis of cell cycle dependent HIV-1 replication. Implications for control of virus burden.
abstract: Research is beginning to yield insight into determinants which govern cell cycle dependence of provirus establishment by the onco-retroviruses. In the case of HIV-1, nucleophilic components associated with the viral preintegration complex facilitate mitosis independent nuclear localization of viral DNA and provirus establishment. Differences in the metabolic activity between G0 T cells and macrophages, the two primary targets for HIV-1 infection, lead to significantly different outcomes with regards to provirus establishment following infection of these cells. Thus, macrophages appear fully permissive to productive HIV-1 replication while non-dividing (G0 T cells) restrict virus replication at a step which proceeds nuclear import of viral DNA. The requirement for T cell activation in productive HIV-1 replication has important implications for the relationship between immune activation and virus burden. It remains to be determined whether modulating the immune activation status of the infected individual may provide an opportunity for modulating virus burden and influencing disease course.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-5120, USA.
authors.forename: M
authors.initials: M
authors.lastname: Stevenson
authors.forename: B
authors.initials: B
authors.lastname: Brichacek
authors.forename: N
authors.initials: N
authors.lastname: Heinzinger
authors.forename: S
authors.initials: S
authors.lastname: Swindells
authors.forename: S
authors.initials: S
authors.lastname: Pirruccello
authors.forename: E
authors.initials: E
authors.lastname: Janoff
authors.forename: M
authors.initials: M
authors.lastname: Emerman
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000503:physiopathology*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008938:Mitosis / Q000276:immunology; D009696:Nucleic Acids / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication
chemical_list: D009696:Nucleic Acids