The Polyomaviridae: Contributions of virus structure to our understanding of virus receptors and infectious entry

Abstract

This review summarizes the fields major findings related to the characterization of polyomavirus structures and to the characterization of virus receptors and mechanisms of host cell invasion. Four members of the family that have received the most attention in this regard are the mouse polyomavirus (mPyV), the monkey polyomavirus SV40, and the two human polyomaviruses, JCV and BKV. The structures of both the mPyV and SV40 alone and in complex with receptor fragments have been solved to high resolution. The majority of polyomaviruses recognize terminal sialic acid in either an α 2,3 linkage or an α 2,6 linkage to the underlying galactose. Studies on virus structure, receptor utilization and mechanisms of entry have led to new insights into how these viruses interact in an active way with cells to ensure the nuclear delivery and expression of their genomes. Critical work on virus entry has led to the discovery of a pH neutral endocytic compartment that accepts cargo from caveolae and to novel roles for endoplasmic reticulum (ER) associated factors in virus uncoating and penetration of ER membranes. This review will summarize the major findings and compare and contrast the mechanisms used by these viruses to infect cells.

Lipid-Mediated Endocytosis

“…The crystal structures available for the toxins and viruses in association with their receptors show that 2-3 of the saccharides in the glycosphingolipid contact the protein subunit directly (Merritt et al 1994;Stehle et al 1994;Neu et al 2008Neu et al , 2009. Although the affinity of glycosphingolipid binding is often relatively low, the avidity of toxin and virus binding to membrane bilayers and cells is high because of the multivalency of binding (Mammen et al 1998).…”

Gangliosides Have a Functional Role during Rotavirus Cell Entry

“…Besides these important biological functions they are also used as receptors for many viruses, including different members of the Polyomaviridae family (simian virus 40, murine polyomavirus, BK virus, JC virus, Merkel cell polyomavirus) (14,15), paramyxoviruses (Newcastle disease virus and Sendai virus) (16), bovine adeno-associated virus (17), influenza virus (18), murine norovirus (19), and rotavirus (10,20).…”

Abl Family Tyrosine Kinases Regulate Sialylated Ganglioside Receptors for Polyomavirus

“…Abl family kinases regulate cell surface sialidase activity. Primate, murine, and human PyVs bind to receptors with a terminal sialic acid(s) linked to galactose (37). The sialylation state of plasma membrane glycolipids and glycoproteins is regulated by sialyltransferases within the Golgi apparatus that add sialic acid moieties to precursors and by sialidases in the plasma membrane, lysosome, and cytosol that remove them (33-35, 55, 56).…”