Mechanism and complex roles of HSC70/HSPA8 in viral entry

Abstract

The process of viruses entering host cells is complex, involving multiple aspects of the molecular organization of the cell membrane, viral proteins, the interaction of receptor molecules, and cellular signaling. Most viruses depend on endocytosis for uptake, when viruses reach the appropriate location, they are released from the vesicles, undergo uncoating, and release their genomes. Heat shock cognate protein 70(HSC70): also known as HSPA8, a protein involved in mediating clathrin-mediated endocytosis (CME), is involved in various viral entry processes. In this mini-review, our goal is to provide a summary of the function of HSC70 in viral entry. Understanding the interaction networks of HSC70 with viral proteins helps to provide new directions for targeted therapeutic strategies against viral infections.

Keywords: Function 5; HSC70 1; Interaction 4; Receptor protein 6; Virus entry 2; Virus protein 3.

Fig. 1

The functions of HSC70 in viral entry. As a chaperone protein, HSC70 is hijacked to participate in the process of viral invasion into host cells. Membrane-anchored HSC70 acts as a binding receptor, post-attachment receptor, and potential attachment factor, facilitating the entry of DENV-2, DENV-4, PRRSV, CHIKV, IBV, and rotavirus into host cells. Once inside the host cell, most viruses are encapsulated within endosomes and may penetrate into the cytoplasm at various stages of endosomal maturation. With the assistance of HSC70, JEV penetrates from late endosomes (taking late endosomes as an example) into the cytoplasm and, with the help of HSC70, completes uncoating at the appropriate location.