title: Asymmetric HIV-1 co-receptor use and replication in CD4(+) T lymphocytes.
abstract: Susceptibility to infection by the human immunodeficiency virus type-1 (HIV-1), both in vitro and in vivo, requires the interaction between its envelope (Env) glycoprotein gp120 Env and the primary receptor (R), CD4, and Co-R, either CCR5 or CXCR4, members of the chemokine receptor family. CCR5-dependent (R5) viruses are responsible for both inter-individual transmission and for sustaining the viral pandemics, while CXCR4-using viruses, usually dualtropic R5X4, emerge in ca. 50% of individuals only in the late, immunologically suppressed stage of disease. The hypothesis that such a major biological asymmetry is explained exclusively by the availability of cells expressing CCR5 or CXCR4 is challenged by several evidences. In this regard, binding of the HIV-1 gp120 Env to the entry R complex, i.e. CD4 and a chemokine R, leads to two major events: virion-cell membrane fusion and a cascade of cell signaling. While the fusion/entry process has been well defined, the role of R/Co-R signaling in the HIV-1 life cycle has been less characterized. Indeed, depending on the cellular model studied, the capacity of HIV-1 to trigger a flow of events favoring either its own latency or replication remains a debated issue. In this article, we will review the major findings related to the role of HIV R/Co-R signaling in the steps following viral entry and leading to viral spreading in CD4(+) T lymphocytes.
authors.affiliation: AIDS Immunopathogenesis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Samanta A
authors.initials: SA
authors.lastname: Mariani
authors.forename: Elisa
authors.initials: E
authors.lastname: Vicenzi
authors.forename: Guido
authors.initials: G
authors.lastname: Poli
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007107:Immune System; D015847:Interleukin-4 / Q000378:metabolism; D009154:Mutation; D019713:Receptors, CCR5 / Q000737:chemistry; D019718:Receptors, CXCR4 / Q000737:chemistry; D019707:Receptors, Chemokine / Q000378:metabolism*; D015398:Signal Transduction; D015302:Simian Immunodeficiency Virus / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism
chemical_list: D018925:Chemokines; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D015847:Interleukin-4