Heat Shock Cognate Protein 70 Is Involved in Rotavirus Cell Entry

Abstract

In this work, we have identified the heat shock cognate protein (hsc70) as a receptor candidate for rotaviruses. hsc70 was shown to be present on the surface of MA104 cells, and antibodies to this protein blocked rotavirus infectivity, while not affecting the infectivity of reovirus and poliovirus. Preincubation of the hsc70 protein with the viruses also inhibited their infectivity. Triple-layered particles (mature virions), but not double-layered particles, bound hsc70 in a solid-phase assay, and this interaction was blocked by monoclonal antibodies to the virus surface proteins VP4 and VP7. Rotaviruses were shown to interact with hsc70 at a postattachment step, since antibodies to hsc70 and the protein itself did not inhibit the virus attachment to cells. We propose that the functional rotavirus receptor is a complex of several cell surface molecules that include, among others, hsc70.

Integrin-Using Rotaviruses Bind α2β1 Integrin α2 I Domain via VP4 DGE Sequence and Recognize αXβ2 and αVβ3 by Using VP7 during Cell Entry

“…Adenovirus recognition of ␣V␤3 leads to both clathrin-mediated endocytosis and macropinocytosis of virus (37). The ability of heat shock cognate protein 70 to inhibit the infectivity of integrin-using rotaviruses (19) is consistent with usage of the clathrin pathway, as this heat shock protein facilitates vesicle uncoating and clathrin recycling to the cell membrane (25). Alternatively, as caveolin-1 associates with ␣2␤1 and ␣V␤3 (54) and echovirus 1 binding to ␣2␤1 results in virus internalization through caveolae (36), rotavirus recognition of ␣2␤1 and ␣V␤3 could lead to rotavirus entry through caveolae.…”

Virus Infection and Lipid Rafts

“…Group A rotaviruses infect epithelial cells via a complex of several cell molecules, including gangliosdes, glycoproteins, Hsc70 protein, and a V b 3 integrin, that are present in membrane lipid rafts. 13,14) Echovirus type 1 initiates infection by binding to a 2 b 1 -integrin, which induces activation of caveola endocytosis. The involvement of membrane lipid rafts in echovirus type 1 infection has been suggested findings that echovirus type 1 infection is inhibited by treatment with methyl-b-cyclodextrin and by the expression of a dominant negative caveolin.…”

“…The involvement of membrane lipid rafts in entry of nonenveloped viruses has been demonstrated by simian virus 40 (SV40) [6][7][8][9][10][11][12] (belonging to the Papovaviridae family), rotavirus 13,14) (belonging to the Reoviridae family), echovirus type 1 15) (belonging to the Picornaviridae family), enterovirus [16][17][18] (belonging to the Picornaviridae family), species C human adenovirus (HAdV) 19) (belong to the Adenoviridae family), and rhinovirus 20) (belonging to the Picornaviridae family).…”

Expression patterns of two heat-shock cognate 70 genes during immune responses and larval development of the Chinese mitten crab Eriocheir sinensis

“…HSC70s play essential roles in protein metabolism (Park et al, 2001), and they function as molecular chaperones or housekeeping proteins in many cellular physiological processes (Guerrero et al, 2002;Yan et al, 2010;Iwanaga et al, 2014). The identification and characterization of HSC70s may provide valuable information for farming freshwater crabs.…”

“…The cognate forms of HSP70, the heat-shock cognate proteins 70 (HSC70s), are abundantly and ubiquitously expressed in all cells, are present under most conditions, and may or may not be influenced by stress (Daugaard et al, 2007;Zhang and Denlinger, 2010). HSC70s function as molecular chaperons or housekeeping proteins, and have been shown to be involved in many cellular physiological processes, such as protein folding in the cytoplasm, cell survival during neurulation, prevention of apoptosis induced by virus infections, and trafficking of receptors and coated vesicles (Guerrero et al, 2002;Yan et al, 2010;Iwanaga et al, 2014). HSC70s also act as molecular chaperones to regulate MeVg2 expression in the greasyback shrimp (Metapenaeus ensis) (Chan et al, 2014).…”