Peptide inhibition of human cytomegalovirus infection

Melnik, Lilia I; Garry, Robert F; Morris, Cindy A

HCMV has a double-stranded DNA genome of 235 kb encoding approximately 165 genes [7] . It has a very broad cellular tropism resulting in potential infection of nearly every organ system. The ability of HCMV to enter a wide range of cell types involves a complex interaction between several viral envelope glycoproteins and host cell surface receptors, although the entry of herpesviruses into host cells is still poorly understood. The HCMV virion envelope contains at least 20 virusencoded glycoproteins that are involved in cell attachment and penetration [8] . Of these, glycoprotein B (gB) is the most abundant glycoprotein [9] and is highly conserved among the Herpesviridae [10] . Glycoprotein B plays a critical role in the HCMV entry process. Initially, gB along with gM/gN, is involved in tethering of virions to heparan sulfate proteoglycans (HSPG) on the surface of host cells. The short interaction of HCMV with HSPG is followed by more stable interactions with one or more viral cellular receptors, namely epidermal growth factor receptor (EGFR) [11] , platelet-derived growth factor receptor (PDGFR) [12] , and toll-like receptor TLR-2 [13] . Glycoprotein B also interacts with integrin αvβ3, a coreceptor that enhances HCMV entry [14] . Integrins are known to synergise with EGFR as well as with other receptors to activate signal transduction pathways [15] [16] [17] . To complete the entry process, both viral and cellular membranes fuse, allowing the release of virion-associated tegument and capsid proteins into the cytoplasm. This final step of viral entry into host cells requires gB and the gH/gL complex [18] [19] [20] [21] .