Structural and biochemical analysis reveals that ASFV protein pB602L is a novel viral molecular chaperone essential for the folding of viral proteins p72 and pS273R, offering potential targets for antiviral strategies.
African swine fever (ASF), caused by the ASF virus (ASFV), is a highly lethal disease in pigs and poses a serious threat to global swine health and the pork industry. The non-structural ASFV protein pB602L has been reported to facilitate the folding of the major capsid protein p72, and its absence leads to the formation of structurally incomplete viral particles. Despite its critical role in ASFV assembly, the structure and molecular mechanism of pB602L remain poorly understood. In this study, we analyzed the three-dimensional structure of pB602L using cryogenic electron microscopy (cryo-EM) and investigated its chaperone activity. Biochemical and cryo-EM analyses revealed that pB602L comprises distinct N- and C-terminal domains and forms a homodimer. The N-terminal domain (residues 1-315) mediates dimerization primarily through hydrophobic interactions, whereas the C-terminal domain (residues 316-530) exhibits ATPase activity and interacts with unfolded client proteins. Both domains are indispensable for the chaperone function of pB602L. Importantly, we identified the ASFV cysteine protease pS273R, essential for core-shell assembly, as a novel client of pB602L. These findings suggest that pB602L represents a new class of viral molecular chaperones that assist in the folding of both p72 and pS273R. Our study enhances the understanding of ASFV molecular pathogenesis and highlights potential targets for antiviral strategies and vaccine development.
Wei et al. (Sun,) studied this question.