Tumor cell surface receptors for vaccinia virus entry

Tumor cell surface receptors for vaccinia virus entry comprise a diverse set of molecules that facilitate the attachment and internalization of the vaccinia virus (VACV) into host cells, a process central to oncolytic virotherapy. The virus initially attaches to the cell surface via glycosaminoglycans (GAGs), such as heparan sulfate and chondroitin sulfate, which are often upregulated in various cancers (Schmidt et al., 2012). Following attachment, VACV frequently employs 'apoptotic mimicry,' where phosphatidylserine on the viral envelope engages host phosphatidylserine receptors like the TIM and TAM families to trigger macropinocytosis (Mercer & Helenius, 2008). Additionally, specific protein receptors, including integrin beta-1 (ITGB1) and CD98, are required for the activation of the viral entry fusion complex (EFC) to mediate membrane fusion (Izmailyan et al., 2012; Schroeder et al., 2019). These receptors serve as the primary gateway for therapeutic oncolytic viruses, such as Pexastimogene devacirepvec (Pexa-Vec), to selectively infect and lyse tumor cells (Kirn & Thorne, 2009). While the broad expression of these receptors allows for the treatment of diverse tumor types, it also presents challenges for achieving absolute tumor specificity and avoiding off-target effects.

Other names

Vaccinia virus entry factorsVACV receptorsOncolytic vaccinia virus targetsPoxvirus entry mediators

Binding of viral envelope proteins to host cell surface glycosaminoglycans and protein receptors, triggering membrane fusion or macropinocytosis to deliver the viral core into the cytoplasm for replication and subsequent oncolysis.