title: KSHV attachment and entry are dependent on αVβ3 integrin localized to specific cell surface microdomains and do not correlate with the presence of heparan sulfate.
abstract: Cellular receptors for KSHV attachment and entry were characterized using tyramide signal amplification (TSA)-enhanced confocal microscopy. Integrins αVβ3, αVβ5 and α3β1 were detected on essentially all the actin-based cell surface microdomains that initially bind KSHV, while the presence of CD98 and heparan sulfate (HS), the putative attachment receptor, was more variable. KSHV bound to the same cell surface microdomains with and without HS indicating that initial attachment of KSHV is not dependent on HS and that receptors other than HS can mediate attachment. A human salivary gland (HSG) epithelial line was identified, which lacks αVβ3 but expresses high levels of HS, α3β1 and other putative KSHV receptors. These cells were resistant to KSHV binding and infection. Reconstitution of cell surface αVβ3 rendered HSG cells highly susceptible to KSHV infection, demonstrating a critical role for αVβ3 in the binding and entry of KSHV that is not shared with other proposed receptors.
authors: Seattle Children׳s Research Institute, 1900 Ninth Avenue, 8th Floor, Seattle, WA 98101, USA. Electronic address: Jacques.garrigues@seattlechildrens.org.
authors: H Jacques
authors: HJ
authors: Garrigues
authors: Seattle Children׳s Research Institute, 1900 Ninth Avenue, 8th Floor, Seattle, WA 98101, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA. Electronic address: demaster@mail.med.upenn.edu.
authors: Laura K
authors: LK
authors: DeMaster
authors: Seattle Children׳s Research Institute, 1900 Ninth Avenue, 8th Floor, Seattle, WA 98101, USA. Electronic address: yrubinchikova@pnwu.edu.
authors: Yelena E
authors: YE
authors: Rubinchikova
authors: Seattle Children׳s Research Institute, 1900 Ninth Avenue, 8th Floor, Seattle, WA 98101, USA; Department of Pediatrics, University of Washington, Seattle, WA 98195, USA. Electronic address: timothy.rose@seattlechildrens.org.
authors: Timothy M
authors: TM
authors: Rose
mesh_terms: D006497:Heparan Sulfate / Q000378:metabolism*; D006566:Herpesviridae Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism / Q000821:virology*; D021381:Protein Transport; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D006497:Heparan Sulfate; D039302:Integrin alphaVbeta3; D011991:Receptors, Virus
keywords: Cell surface microdomains; Integrin αVβ3; KSHV; Kaposi׳s sarcoma-associated herpesvirus; Tyramide signal amplification; Virus attachment; Virus binding; Virus entry