title: HIV-1 compartmentalization in diverse leukocyte populations during antiretroviral therapy.
abstract: CD4+ T lymphocytes are the primary target of human immunodeficiency virus type 1 (HIV-1), but there is increasing evidence that other immune cells in the blood, including CD8+ T lymphocytes and monocytes, are also productively infected. The extent to which these additional cellular reservoirs contribute to ongoing immunodeficiency and viral persistence during therapy remains unclear. In this study, we conducted a detailed investigation of HIV-1 diversity and genetic structure in CD4+ T cells, CD8+ T cells, and monocytes of 13 patients receiving highly active antiretroviral therapy (HAART). Analysis of molecular variance and nonparametric tests performed on HIV-1 envelope sequences provided statistically significant evidence of viral compartmentalization in different leukocyte populations. Signature pattern analysis and predictions of coreceptor use provided no evidence that selection arising from viral tropism was responsible for the genetic structure observed. Analysis of viral genetic variation in different leukocyte populations demonstrated the action of founder effects as well as significant variation in the extent of genetic differentiation between subpopulations among patients. In the absence of evidence for leukocyte-specific selection, these features were supportive of a metapopulation model of HIV-1 replication as described previously among HIV-1 populations in the spleen. Compartmentalization of the virus in different leukocytes may have significant implications for current models of HIV-1 population genetics and contribute to the highly variable way in which drug resistance evolves in different individuals during HAART.
authors.affiliation: Center for Virus Research, Westmead Millennium Institute, Westmead Hospital, The University of Sydney, Darcy Road, Westmead, Sydney NSW 2145, Australia.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Potter
authors.forename: Philippe
authors.initials: P
authors.lastname: Lemey
authors.forename: Guillaume
authors.initials: G
authors.lastname: Achaz
authors.forename: Choo Beng
authors.initials: CB
authors.lastname: Chew
authors.forename: Anne-Mieke
authors.initials: AM
authors.lastname: Vandamme
authors.forename: Dominic E
authors.initials: DE
authors.lastname: Dwyer
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Saksena
mesh_terms: D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002451:Cell Compartmentation / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D014644:Genetic Variation / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: D044966:Anti-Retroviral Agents; D014759:Viral Envelope Proteins