beta 1 Integrin Mediates Internalization of Mammalian Reovirus

• Published in: Journal of virology Vol. 80; no. 6; pp. 2760 - 2770
• Main Authors: Maginnis, Melissa S, rest, JCraig, Kopecky-Bromberg, Sarah A, Dickeson, SKent, Santoro, Samuel A, Zutter, Mary M, Nemerow, Glen R, Bergelson, Jeffrey M, Dermody, Terence S
• Format: Journal Article
• Language: English
• Published: 01-03-2006
• Subjects: Reovirus
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/JVI.80.6.2760-2770.2006

Reovirus infection is initiated by interactions between the attachment protein sigma 1 and cell surface carbohydrate and junctional adhesion molecule A (JAM-A). Expression of a JAM-A mutant lacking a cytoplasmic tail in nonpermissive cells conferred full susceptibility to reovirus infection, suggesting that cell surface molecules other than JAM-A mediate viral internalization following attachment. The presence of integrin-binding sequences in reovirus outer capsid protein lambda 2, which serves as the structural base for sigma 1, suggests that integrins mediate reovirus endocytosis. A beta 1 integrin-specific antibody, but not antibodies specific for other integrin subunits, inhibited reovirus infection of HeLa cells. Expression of a beta 1 integrin cDNA, along with a cDNA encoding JAM-A, in nonpermissive chicken embryo fibroblasts conferred susceptibility to reovirus infection. Infectivity of reovirus was significantly reduced in beta 1-deficient mouse embryonic stem cells in comparison to isogenic cells expressing beta 1. However, reovirus bound equivalently to cells that differed in levels of beta 1 expression, suggesting that beta 1 integrins are involved in a postattachment entry step. Concordantly, uptake of reovirus virions into beta 1-deficient cells was substantially diminished in comparison to viral uptake into beta 1-expressing cells. These data provide evidence that beta 1 integrin facilitates reovirus internalization and suggest that viral entry occurs by interactions of reovirus virions with independent attachment and entry receptors on the cell surface.