title: Upregulation of human cytomegalovirus by HIV type 1 in human lymphoid tissue ex vivo.
abstract: HIV-1 copathogens are believed to play a critical role in progression to AIDS. Human cytomegalovirus (HCMV) has a high prevalence in the general population and is a common copathogen in HIV-1-infected individuals. Important events in copathogen interactions with HIV-1 take place in lymphoid tissue where critical events in HIV-1 disease occur. Here, we used an experimental system of human lymphoid tissue ex vivo to investigate interactions of HCMV with HIV-1. We inoculated ex vivo blocks of human lymphoid tissue with a recombinant strain of HCMV, expressing the green fluorescent protein, and HIV-1 and monitored viral replication and the phenotype of productively infected cells. HCMV readily replicated in tissue blocks as revealed by the release of HCMV viral DNA and an increasing number of viral-positive cells. Immunophenotyping of HCMV-infected cells showed a preferential infection of activated lymphocytes. The number of these cells significantly increased in HIV-1-coinfected tissues. Accordingly, HCMV replication was enhanced 2- to-3 fold. This upregulation occurred in tissues infected with either CXCR4- or CCR5-utilizing HIV-1. Thus, HIV-1 creates new targets for HCMV, which may explain the strong association of HCMV with HIV-1 infection in vivo. Ex vivo-infected human lymphoid tissue constitutes a model to study the mechanisms of HCMV tissue pathogenesis and its interactions with HIV-1 and this model may provide new targets for anti-HIV-1 therapy.
authors.affiliation: Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. biancoa@mail.nih.gov
authors.forename: Angélique
authors.initials: A
authors.lastname: Biancotto
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Iglehart
authors.forename: Andrea
authors.initials: A
authors.lastname: Lisco
authors.forename: Christophe
authors.initials: C
authors.lastname: Vanpouille
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Grivel
authors.forename: Nell S
authors.initials: NS
authors.lastname: Lurain
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Reichelderfer
authors.forename: Leonid B
authors.initials: LB
authors.lastname: Margolis
mesh_terms: D003587:Cytomegalovirus / Q000235:genetics / Q000254:growth & development*; D004279:DNA, Viral / Q000378:metabolism; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D008214:Lymphocytes / Q000821:virology; D008221:Lymphoid Tissue / Q000821:virology*; D009924:Organ Culture Techniques; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D049452:Green Fluorescent Proteins