Amino Acid Variation at VP1-145 of Enterovirus 71 Determines Attachment Receptor Usage and Neurovirulence in Human Scavenger Receptor B2 Transgenic Mice

Attachment receptors expressed on the host cell surface are thought to enhance EV71 infection by increasing the chance of encountering true receptors. Although this has been confirmed using cell culture for some viruses, the importance of attachment receptors in vivo is unknown. This report provides an unexpected answer to this question. We demonstrated that the VP1-145G virus binds to HS and shows an attenuated phenotype in an hSCARB2-dependent animal infection model. HS is highly expressed in cells that express hSCARB2 at low or undetectable levels. Our data indicate that HS binding directs VP1-145G virus toward abortive infection and keeps virus away from hSCARB2-positive cells. Thus, although the ability of VP1-145G virus to use HS might be an advantage in replication in certain cultured cells, it becomes a serious disadvantage in replication in vivo . This adsorption is thought to be a major mechanism of attenuation associated with attachment receptor usage.