title: Blocking of integrins inhibits HIV-1 infection of human cervical mucosa immune cells with free and complement-opsonized virions.
abstract: The initial interaction between HIV-1 and the host occurs at the mucosa during sexual intercourse. In cervical mucosa, HIV-1 exists both as free and opsonized virions and this might influence initial infection. We used cervical explants to study HIV-1 transmission, the effects of opsonization on infectivity, and how infection can be prevented. Complement opsonization enhanced HIV-1 infection of dendritic cells (DCs) compared with that by free HIV-1, but this increased infection was not observed with CD4(+) T cells. Blockage of the α4-, β7-, and β1-integrins significantly inhibited HIV-1 infection of both DCs and CD4(+) T cells. We found a greater impairment of HIV-1 infection in DCs for complement-opsonized virions compared with that of free virions when αM/β2- and α4-integrins were blocked. Blocking the C-type lectin receptor macrophage mannose receptor (MMR) inhibited infection of emigrating DCs but had no effect on CD4(+) T-cell infection. We show that blocking of integrins decreases the HIV-1 infection of both mucosal DCs and CD4(+) T cells emigrating from the cervical tissues. These findings may provide the basis of novel microbicidal strategies that may help limit or prevent initial infection of the cervical mucosa, thereby reducing or averting systemic HIV-1 infection.
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Veronica
authors.initials: V
authors.lastname: Tjomsland
authors.forename: Rada
authors.initials: R
authors.lastname: Ellegård
authors.forename: Preben
authors.initials: P
authors.lastname: Kjölhede
authors.forename: Ninni Borendal
authors.initials: NB
authors.lastname: Wodlin
authors.forename: Jorma
authors.initials: J
authors.lastname: Hinkula
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002584:Cervix Uteri / Q000166:cytology / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control / Q000635:transmission; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D039441:Integrin alpha4 / Q000378:metabolism; D039641:Integrin beta Chains / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology; D009924:Organ Culture Techniques; D011971:Receptors, Immunologic / Q000378:metabolism
chemical_list: D039641:Integrin beta Chains; D019012:Integrin beta1; D016023:Integrins; D011971:Receptors, Immunologic; C091368:integrin beta7; D039441:Integrin alpha4; D003165:Complement System Proteins
keywords: CD4+ T cells; Complement system; DCs; HIV; Integrins