title: HIV latency. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection.
abstract: Antiretroviral treatment (ART) of HIV infection suppresses viral replication. Yet if ART is stopped, virus reemerges because of the persistence of infected cells. We evaluated the contribution of infected-cell proliferation and sites of proviral integration to HIV persistence. A total of 534 HIV integration sites (IS) and 63 adjacent HIV env sequences were derived from three study participants over 11.3 to 12.7 years of ART. Each participant had identical viral sequences integrated at the same position in multiple cells, demonstrating infected-cell proliferation. Integrations were overrepresented in genes associated with cancer and favored in 12 genes across multiple participants. Over time on ART, a greater proportion of persisting proviruses were in proliferating cells. HIV integration into specific genes may promote proliferation of HIV-infected cells, slowing viral decay during ART.
authors.affiliation: Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA. University of Washington, Seattle, WA, USA.
authors.forename: Thor A
authors.initials: TA
authors.lastname: Wagner
authors.affiliation: Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA. University of Washington, Seattle, WA, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: McLaughlin
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Kavita
authors.initials: K
authors.lastname: Garg
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Charles Y K
authors.initials: CY
authors.lastname: Cheung
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: Brendan B
authors.initials: BB
authors.lastname: Larsen
authors.affiliation: Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA.
authors.forename: Sheila
authors.initials: S
authors.lastname: Styrchak
authors.affiliation: Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA.
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Huang
authors.affiliation: University of Washington, Seattle, WA, USA. Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Edlefsen
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.affiliation: Seattle Children's Research Institute, 1900 9th Avenue, Seattle, WA 98101, USA. University of Washington, Seattle, WA, USA. lfrenkel@uw.edu.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Frenkel
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D049109:Cell Proliferation; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D052138:Genes, Neoplasm; D056426:Genetic Loci; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D010802:Phylogeny; D016662:Virus Integration; D017735:Virus Latency; D014779:Virus Replication; D054299:env Gene Products, Human Immunodeficiency Virus / Q000145:classification / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; C491123:BACH2 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D054299:env Gene Products, Human Immunodeficiency Virus