Amino acid domains 280-297 of VP6 and 531-554 of VP4 are implicated in heat shock cognate protein hsc70-mediated rotavirus infection.
The rotavirus infection mechanism seems to be a multi-step process which is still not fully understood. The heat shock cognate protein hsc70 has been proposed as being a co-receptor molecule for rotavirus entry into susceptible cells. In this work, an attempt was made to determine the existence of possible domains for VP4 and VP6 binding to hsc70. We selected amino acid sequences 531-554 from VP4 and 280-297 from VP6 on the basis of already recognized sequences for binding to hsc70. This study determined that DLPs and synthetic peptides from VP6 (aa 280-297) and VP4 (aa 531-554), individually or in combination, inhibited rotavirus RRV, YM and WA entry into MA104 and Caco-2 cells in an additive and dose-dependent manner. Hyperimmune sera against these synthetic peptides blocked infection by infectious TLPs. Capture ELISA results showed that DLPs interact with hsc70, probably through VP6 as the specific interaction between hcs70 and DLPs was disrupted by a VP6 peptide. These results suggest that VP6 takes part during rotavirus cell entry by binding to hsc70. This, as well as previous work, provides insight concerning the function of hsc70 within a multi-step model of rotavirus entry.
Gualtero
D F
DF
Departamento de Ciencias Fisiológicas, Facultad de Medicina-Instituto de Biotecnología, Universidad Nacional de Colombia, Bogotá, Colombia.
Guzmán
F
F
Acosta
O
O
Guerrero
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry / Q000378:metabolism; D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor / Q000821:virology; D004847:Epithelial Cells / Q000821:virology; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000821:virology; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D012401:Rotavirus / Q000472:pathogenicity*
D000956:Antigens, Viral; D036022:Capsid Proteins; D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D010455:Peptides; C060339:VP4 protein, Rotavirus; C061332:VP6 protein, Rotavirus