title: R5 and X4 HIV envelopes induce distinct gene expression profiles in primary peripheral blood mononuclear cells.
abstract: HIV envelope binds to and signals through its primary cellular receptor, CD4, and through a coreceptor, either CC chemokine receptor 5 (CCR5) or CXC chemokine receptor 4 (CXCR4). Here, we evaluate the response of peripheral blood mononuclear cells to a panel of genetically diverse R5 and X4 envelope proteins. Modulation of gene expression was evaluated by using oligonucleotide microarrays. Activation of transcription factors was evaluated by using an array of oligonucleotides encoding transcription factor binding sites. Responses were strongly influenced by coreceptor specificity. Treatment of cells from CCR5delta32 homozygous donors with glycoprotein (gp)120 derived from an R5 virus demonstrated that the majority of responses elicited by R5 envelopes required engagement of CCR5. R5 envelopes, to a greater extent than X4 envelopes, induced the expression of genes belonging to mitogen-activated protein kinase signal transduction pathways and genes regulating the cell cycle. A number of genes induced by R5, but not X4, envelopes were also up-regulated in the resting CD4+ T cell population of HIV-infected individuals. These results suggest that R5 envelope facilitates replication of HIV in the pool of resting CD4+ T cells. Additionally, signaling by R5 gp120 may facilitate the transmission of R5 viruses by inducing a permissive environment for HIV replication.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ccicala@niaid.nih.gov
authors.forename: Claudia
authors.initials: C
authors.lastname: Cicala
authors.forename: James
authors.initials: J
authors.lastname: Arthos
authors.forename: Elena
authors.initials: E
authors.lastname: Martinelli
authors.forename: Nina
authors.initials: N
authors.lastname: Censoplano
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Cruz
authors.forename: Eva
authors.initials: E
authors.lastname: Chung
authors.forename: Sara M
authors.initials: SM
authors.lastname: Selig
authors.forename: Donald
authors.initials: D
authors.lastname: Van Ryk
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Shyla
authors.initials: S
authors.lastname: Jagannatha
authors.forename: Tae Wook
authors.initials: TW
authors.lastname: Chun
authors.forename: Ping
authors.initials: P
authors.lastname: Ren
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D014779:Virus Replication
chemical_list: D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014157:Transcription Factors