Cell surface heparan sulfate is an attachment receptor for grass carp reovirus

Grass carp reovirus (GCRV) causes hemorrhagic disease in grass carp, leading to significant economic losses in China's aquaculture. However, the cellular receptors responsible for the initiation of GCRV infection remain unclear. This study reveals that cell surface heparan sulfate (HS) acts as a crucial attachment receptor for GCRV. Removing HS with heparinase significantly reduces GCRV attachment and infection. Both HS and its homologue, heparin, inhibit the attachment of GCRV to cells. Altering HS levels in cells affects GCRV attachment and infection accordingly. GCRV outer capsid proteins VP5, VP56, and VP35, as well as purified GCRV virions, directly bind to HS. Pretreating GCRV with heparin or feeding grass carp with feed containing heparin significantly reduces mortality caused by GCRV infection. Collectively, these results highlight the crucial role of HS as an attachment receptor for GCRV and therefore provide a promising target for the prevention and control of this virus.