title: β5 integrin is the major contributor to the αVintegrin-mediated blockade of HIV-1 replication.
abstract: Monocytes and macrophages are targets of HIV-1 infection and play critical roles in multiple aspects of viral pathogenesis. During the differentiation of monocytes to macrophages, adhesion molecules such as integrins are upregulated; therefore, they provide signals that control the process and subsequently may render macrophages more susceptible to HIV-1 infection. Previous work demonstrated that blocking α(v)-containing integrins triggered a signal transduction pathway leading to the inhibition of NF-κB-dependent HIV-1 transcription. In this paper, we show the influence of the different α(v)-coupled β integrins in HIV-1 replication in macrophages. Inhibition of β integrins, either by specific mAbs, small arginine-glycine-aspartic acid (RGD) mimetic compounds, or RNA interference, showed that integrin β(5) was the major contributor to the integrin-mediated blockade of HIV-1 replication. Importantly, such inhibition did not induce changes in cell adhesion to the substrate. In conclusion, our results reveal a significant role of the integrin dimer α(v)β(5) in HIV-1 infection of macrophages.
authors.affiliation: IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Ballana
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pauls
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Françoise
authors.initials: F
authors.lastname: Perron-Sierra
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Tucker
authors.forename: José A
authors.initials: JA
authors.lastname: Esté
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D039641:Integrin beta Chains / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000821:virology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D055503:Protein Multimerization / Q000235:genetics / Q000276:immunology*; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*
chemical_list: D000998:Antiviral Agents; D039641:Integrin beta Chains; D021122:Protein Subunits; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; C084344:integrin beta5