title: Understanding Factors That Modulate the Establishment of HIV Latency in Resting CD4+ T-Cells In Vitro.
abstract: Developing robust in vitro models of HIV latency is needed to better understand how latency is established, maintained and reversed. In this study, we examined the effects of donor variability, HIV titre and co-receptor usage on establishing HIV latency in vitro using two models of HIV latency. Using the CCL19 model of HIV latency, we found that in up to 50% of donors, CCL19 enhanced latent infection of resting CD4+ T-cells by CXCR4-tropic HIV in the presence of low dose IL-2. Increasing the infectious titre of CXCR4-tropic HIV increased both productive and latent infection of resting CD4+ T-cells. In a different model where myeloid dendritic cells (mDC) were co-cultured with resting CD4+ T-cells, we observed a higher frequency of latently infected cells in vitro than CCL19-treated or unstimulated CD4+ T-cells in the presence of low dose IL-2. In the DC-T-cell model, latency was established with both CCR5- and CXCR4-tropic virus but higher titres of CCR5-tropic virus was required in most donors. The establishment of latency in vitro through direct infection of resting CD4+ T-cells is significantly enhanced by CCL19 and mDC, but the efficiency is dependent on virus titre, co-receptor usage and there is significant donor variability.
authors.affiliation: Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Anderson
authors.affiliation: Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Talia M
authors.initials: TM
authors.lastname: Mota
authors.affiliation: Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Evans
authors.affiliation: Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Nitasha
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Simin D
authors.initials: SD
authors.lastname: Rezaei
authors.affiliation: Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Karey
authors.initials: K
authors.lastname: Cheong
authors.affiliation: Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Ajantha
authors.initials: A
authors.lastname: Solomon
authors.affiliation: Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Fiona
authors.initials: F
authors.lastname: Wightman
authors.affiliation: Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.|Department of Infectious Diseases, Monash University and Alfred Hospital, Melbourne, Victoria, Australia.
authors.forename: Paul U
authors.initials: PU
authors.lastname: Cameron
authors.affiliation: Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.|Department of Infectious Diseases, Monash University and Alfred Hospital, Melbourne, Victoria, Australia.
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000276:immunology / Q000494:pharmacology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D018448:Models, Immunological; D019713:Receptors, CCR5 / Q000276:immunology; D019718:Receptors, CXCR4 / Q000276:immunology; D017735:Virus Latency / Q000187:drug effects / Q000276:immunology*
chemical_list: C584933:CCR5 protein, human; C527276:CXCR4 protein, human; D054415:Chemokine CCL19; D007376:Interleukin-2; D019713:Receptors, CCR5; D019718:Receptors, CXCR4