title: Integrins as Herpesvirus Receptors and Mediators of the Host Signalosome.
abstract: The repertoire of herpesvirus receptors consists of nonintegrin and integrin molecules. Integrins interact with the conserved glycoproteins gH/gL or gB. This interaction is a conserved biology across the Herpesviridae family, likely directed to promote virus entry and endocytosis. Herpesviruses exploit this interaction to execute a range of critical functions that include (a) relocation of nonintegrin receptors (e.g., herpes simplex virus nectin1 and Kaposi's sarcoma-associated herpesvirus EphA2), or association with nonintegrin receptors (i.e., human cytomegalovirus EGFR), to dictate species-specific entry pathways; (b) activation of multiple signaling pathways (e.g., Ca2+release, c-Src, FAK, MAPK, and PI3K); and (c) association with Rho GTPases, tyrosine kinase receptors, Toll-like receptors, which result in cytoskeletal remodeling, differential cell type targeting, and innate responses. In turn, integrins can be modulated by viral proteins (e.g., Epstein-Barr virus LMPs) to favor spread of transformed cells. We propose that herpesviruses evolved a multipartite entry system to allow interaction with multiple receptors, including integrins, required for their sophisticated life cycle.
authors: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy; email: gabriella.campadelli@unibo.it.
authors: Gabriella
authors: G
authors: Campadelli-Fiume
authors: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, and Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130; email: ayuroc@lsuhsc.edu.
authors: Donna
authors: D
authors: Collins-McMillen
authors: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy; email: gabriella.campadelli@unibo.it.
authors: Tatiana
authors: T
authors: Gianni
authors: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, and Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130; email: ayuroc@lsuhsc.edu.|Feist-Weiller Cancer Center and Center for Excellence in Arthritis and Rheumatology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130.
authors: Andrew D
authors: AD
authors: Yurochko
mesh_terms: D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D015398:Signal Transduction; D018139:Simplexvirus / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D016023:Integrins; D011991:Receptors, Virus
keywords: EBV; HCMV; HSV; KSHV; integrins; signal transduction