Indeed, some reports have demonstrated that the cleavage of the carboxyl-terminal KDEL motif is critical for secretory transport of GRP78 toward the cell surface [15]; our results indicated that the cleavage of the KDEL, an ER-retention signal, is required for cytoplasmic GRP78 to participate in the folding, assembly and transport of viral particles during the virus infection cycle. This evidence concerns the gene HSPA5 and viral infectious disease.