Host cell surface glycans and entry factors for vaccinia virus (VACV entry factors)

Host cell surface glycans and entry factors for vaccinia virus (VACV) comprise a diverse set of molecules that the virus exploits to attach to and enter host cells. Primary attachment is mediated by viral proteins such as D8, A27, and H3 binding to glycosaminoglycans like heparan sulfate and chondroitin sulfate (Schmidt et al., 2012, PLoS Pathogens). Following attachment, the virus utilizes various host proteins, including integrin beta-1, CD98, and the AXL receptor tyrosine kinase, to trigger macropinocytosis or direct membrane fusion (Mercer and Helenius, 2008, Science). These factors are critical for the infection cycle of orthopoxviruses, including variola virus (smallpox) and monkeypox virus (Mpox). The entry process is complex, involving a highly conserved Entry Fusion Complex (EFC) that interacts with the host membrane after initial tethering (Moss, 2012, Virology). While these host factors are essential for viral entry, they also perform vital physiological roles in cell signaling, adhesion, and homeostasis. This dual role makes them challenging therapeutic targets, as inhibition may lead to significant side effects. Nevertheless, research into these factors aims to develop entry inhibitors that can provide broad-spectrum protection against poxvirus infections by blocking the initial stages of the viral life cycle.

Other names

Vaccinia virus receptorsPoxvirus entry factorsVACV attachment factorsHeparan sulfate proteoglycansChondroitin sulfateIntegrin beta-1AXL receptor tyrosine kinaseCD98

Competitive inhibition of viral attachment to cell-surface glycosaminoglycans and pharmacological blockade of host signaling pathways, such as those mediated by AXL or integrins, which are required for viral endocytosis and membrane fusion.