Interaction of Human Tumor Viruses with Host Cell Surface Receptors and Cell Entry

Abstract

Currently, seven viruses, namely Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpes virus (KSHV), high-risk human papillomaviruses (HPVs), Merkel cell polyomavirus (MCPyV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T cell lymphotropic virus type 1 (HTLV-1), have been described to be consistently associated with different types of human cancer. These oncogenic viruses belong to distinct viral families, display diverse cell tropism and cause different malignancies. A key to their pathogenicity is attachment to the host cell and entry in order to replicate and complete their life cycle. Interaction with the host cell during viral entry is characterized by a sequence of events, involving viral envelope and/or capsid molecules as well as cellular entry factors that are critical in target cell recognition, thereby determining cell tropism. Most oncogenic viruses initially attach to cell surface heparan sulfate proteoglycans, followed by conformational change and transfer of the viral particle to secondary high-affinity cell- and virus-specific receptors. This review summarizes the current knowledge of the host cell surface factors and molecular mechanisms underlying oncogenic virus binding and uptake by their cognate host cell(s) with the aim to provide a concise overview of potential target molecules for prevention and/or treatment of oncogenic virus infection.

Human papillomavirus molecular biology

“…Virions bind initially to heparan sulfate proteoglycans (HSPGs), which serve as primary attachment receptors on basal cells or exposed basement membrane resulting from epithelial trauma or permeabilization [39]. Initial L1 attachment to HSPGs induces conformational changes in the virus capsid ultimately resulting in loss of affinity for the primary receptor and transfer of the virus to an as of yet poorly characterized entry receptor.…”

CIB1: a small protein with big ambitions

“…Another interesting study describes a role for CIB1 in the regulation of macropinocytosis and cellular entry of Kaposi's sarcoma-associated herpes virus (KSHV; also k n o w na sh u m a nh e r p e sv i r u s8 )( 6 4 ) .K S H Vh a sb e e n linked to several cancers, including Kaposi'ss a r c o m a , primary effusion lymphoma, and multicentric Castleman's disease. To gain entry into host cells, KSHV binds to several cell-surface receptors, including aVintegrinsandtyrosine kinase receptor family member EphA2, which results in activation of intracellular signaling events that promote macropinocytosis and internalization of the virus (78). Of interest, the researchers found that CIB1 directly interacts with EphA2 and that CIB1 depletion significantly reduces KSHV entry and infection of endothelial cells (64).…”

The liver throws the skeleton a bone (resorption factor)

“…The molecular mechanism of hepatitis C virus (HCV) entry has been revealed by genomic and proteomic technologies. (1) First, HCV infection is mediated by HCV complexing with lipoproteins, which interact with heparan sulphate proteoglycans (HSPGs) on the surface of hepatocytes. Following attachment to HSPGs, in the second phase of infection, HCV associates with several specific entry coreceptors, such as CD81, scavenger receptor class B type 1 (SRB1) and claudin 1 (CLDN-1), to prepare the virus for hepatocyte entry.…”