African Swine Fever Virus major capsid p72 Trimers function as a pH sensor during uncoating process of virus endocytosis

AbstractAfrican swine fever virus (ASFV) belongs to nucleocytoplasmic large DNA viruses (NCLDVs), the only member of Asfarviridae. So far, it is revealed that the ASFV uncoating is a pH-dependent process undergone in late endosomes. But, the research on how pH affects capsid stability is limited, and which protein plays an essential role in pH sensing remains unknown. In this study, we identified the main component of the ASFV capsid -- major capsid protein p72, as a pH sensitive residue abundance protein, and it is speculated that the conformational change of the p72 trimer is possibly responsible for the ASFV uncoating process. To test this speculation, we obtained recombinant p72 trimers, treated with the acidic environment that simulated endosomes and displayed structural analysis. The results showed that the p72 trimer depolymerized at low pH. The depolymerization of trimers rationally explains the disassembly mechanism of the ASFV icosahedral capsid in endosomes.