Saffold virus utilizes sulfated glycosaminoglycans and integrin αvβ8 as cooperative attachment receptors for infection, with double knockout of these pathways conferring complete resistance in HeLa cells.
Saffold virus utilizes both sulfated glycosaminoglycans and integrin αVβ8 as cooperative receptors for cellular entry.
Saffold virus (SAFV), a member of the species Cardiovirus saffoldi within the Picornaviridae family, causes acute respiratory and gastrointestinal illnesses as well as hand, foot, and mouth disease. It is also suspected to be associated with neuronal disorders, such as encephalitis and meningitis, in severe cases. Despite its clinical significance, the virus-host interactions underlying SAFV pathogenicity remain largely unknown. Using a genome-wide CRISPR-Cas9 knockout screen, we identify the following receptors for SAFV infection: sulfated glycosaminoglycans (GAGs) and integrin αVβ8. Single knockouts of SLC35B2, an essential gene for sulfated GAG synthesis, or the integrin genes ITGAV or ITGB8 partially reduce SAFV-3 and SAFV-2 susceptibility in HeLa cells, and a double knockout confers complete resistance. Furthermore, we demonstrate that SAFV-3 virions bind directly to sulfated GAGs and integrin αVβ8. Based on these findings, we propose a model of SAFV infection in which sulfated GAGs and integrin αVβ8 act through dual and cooperative pathways to facilitate viral entry.
Okuwa et al. (Mon,) conducted a other in Saffold virus infection. CRISPR-Cas9 knockout of SLC35B2, ITGAV, or ITGB8 vs. Wild-type cells was evaluated on Viral susceptibility and attachment. Saffold virus utilizes sulfated glycosaminoglycans and integrin αvβ8 as cooperative attachment receptors for infection, with double knockout of these pathways conferring complete resistance in HeLa cells.