title: Identification of preferential CD4+ T-cell targets for HIV infection in the cervix.
abstract: A better understanding of the cellular targets of HIV infection in the female genital tract may inform HIV prevention efforts. Proposed correlates of cellular susceptibility include the HIV co-receptor CCR5, peripheral homing integrins, and immune activation. We used a CCR5-tropic pseudovirus to quantify HIV entry into unstimulated endocervical CD4(+) T cells collected by cytobrush. Virus entry was threefold higher into cervix-derived CD4(+) T cells than blood, but was strongly correlated between these two compartments. Cervix-derived CD4(+) T cells expressing CD69, α(4)β(7), or α(4)β(1) were preferential HIV targets; this enhanced susceptibility was strongly correlated with increased CCR5 expression in α(4)β(7)(+) and CD69(+) CD4(+) T cells, and to a lesser extent in α(4)β(1)(+) CD4(+) T cells. Direct binding of gp140 to integrins was not observed, integrin inhibitors had no effect on virus entry, and pseudotypes with an env that preferentially binds α(4)β(7) still demonstrated enhanced entry into α(4)β(1)(+) cells. In summary, a rapid and sensitive HIV entry assay demonstrated enhanced susceptibility of activated endocervical CD4(+) T cells, and those expressing α(4)β(7) or α(4)β(1). This may relate to increased CCR5 expression by these cell subsets, but did not appear to be due to direct interaction of α(4)β(7) or α(4)β(1) with HIV envelope.
authors: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors: V R
authors: VR
authors: Joag
authors: Centre for the AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.|Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors: L R
authors: LR
authors: McKinnon
authors: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors: J
authors: J
authors: Liu
authors: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors: S T
authors: ST
authors: Kidane
authors: Department of Obstetrics and Gynecology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
authors: M H
authors: MH
authors: Yudin
authors: Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.
authors: B
authors: B
authors: Nyanga
authors: Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.
authors: S
authors: S
authors: Kimwaki
authors: Department of Obstetrics and Gynecology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
authors: K E
authors: KE
authors: Besel
authors: Kenyan AIDS Vaccine Initiative, Nairobi, Kenya.
authors: J O
authors: JO
authors: Obila
authors: Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors: S
authors: S
authors: Huibner
authors: Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.|Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: J O
authors: JO
authors: Oyugi
authors: Laboratory of Immune Regulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors: J
authors: J
authors: Arthos
authors: Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.|Kenyan AIDS Vaccine Initiative, Nairobi, Kenya.
authors: O
authors: O
authors: Anzala
authors: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: J
authors: J
authors: Kimani
authors: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.|Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.
authors: M A
authors: MA
authors: Ostrowski
authors: Department of Immunology, University of Toronto, Toronto, Ontario, Canada.|Department of Medicine, University of Toronto, Toronto, Ontario, Canada.|Department of Medicine, University Health Network, Toronto, Ontario, Canada.
authors: R
authors: R
authors: Kaul
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002584:Cervix Uteri / Q000276:immunology / Q000821:virology*; D005260:Female; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D018928:Immunity, Mucosal; D039041:Integrin alpha4beta1 / Q000235:genetics / Q000276:immunology*; D016023:Integrins / Q000235:genetics / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D009928:Organ Specificity; D061251:Primary Cell Culture; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology*; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D053586:Virus Internalization; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D039041:Integrin alpha4beta1; D016023:Integrins; D037181:Lectins, C-Type; D019713:Receptors, CCR5; D011991:Receptors, Virus; D054299:env Gene Products, Human Immunodeficiency Virus; D000099192:CD69 Antigens; C584933:CCR5 protein, human; C097729:gp140 envelope protein, Human immunodeficiency virus 1; C071777:integrin alpha4beta7