Cellular Entry of Polyomaviruses

Abstract

Polyomaviruses (Pys) are nonenveloped DNA tumor viruses that include the murine polyomavirus (mPy), simian virus 40 (SV40), and the human BK, JC, KI, WU, and Merkel Cell viruses. To cause infection, Pys must enter host cells and navigate through various intracellular compartments, where they undergo sequential conformational changes enabling them to uncoat and deliver the DNA genome into the nucleus. The ensuing transcription and replication of the genome leads to lytic infection or cell transformation. In recent years, a more coherent understanding of how Pys are transported from the plasma membrane to the nucleus is starting to emerge. This review will focus on the decisive steps of Py entry, including engagement of the host cell receptor, targeting to the endoplasmic reticulum (ER), penetration across the ER membrane, nuclear entry, and genome release. Strikingly, a number of these steps resemble the intoxication pathway of the AB(5) bacterial toxins. Thus, as Pys and bacterial toxins hijack similar cellular machineries during infection, a general principle appears to guide their entry into host cells.

Insights into the mechanism of action of cidofovir and other acyclic nucleoside phosphonates against polyoma- and papillomaviruses and non-viral induced neoplasia

“…Lactoseries tetrasaccharide c (LSTc) which terminates in a2,6-linked sialic acid was identified as the specific receptor for JCPyV and the presence of a2,6-linked sialic acid correlates with JCPyV cell and tissue infection, including B lymphocytes, kidney, and the glial cells astrocytes and oligodendrocytes Maginnis et al, 2013). PyVs enter into the host cell via a caveolae-mediated endocytic pathway (Tsai and Qian, 2010). In contrast to most PyVs, JCPyV internalization relies on clathrin-dependent receptor-mediated endocytosis and is then sorted to caveosomes.…”

Imperfect Symmetry of Sp1 and Core Promoter Sequences Regulates Early and Late Virus Gene Expression of the Bidirectional BK Polyomavirus Noncoding Control Region

“…HPyV seroprevalence data obtained using the major capsid protein Vp1 as pentamers or virus-like particles indicate that HPyVs infect 50% to 90% of the general human population without known specific signs or symptoms of disease (2)(3)(4)(5)(6)(7). As information about the virology and pathology of the 13 human PyVs is only emerging (8,9), we focused on BK polyomavirus (BKPyV) as a model (10). After primary infection in early childhood, BKPyV persists latently in the renourinary tract with periods of low-level shedding into urine (4,11,12).…”

Role of Cell-Type-Specific Endoplasmic Reticulum-Associated Degradation in Polyomavirus Trafficking

“…The major capsid protein, VP1, oligomerizes into pentamers during virion production and makes up the outer shell of the particle, with 72 pentamers stabilized by inter-and intra-disulfide bonds (10). It is believed that these disulfide bonds become reduced and/or isomerized by host disulfide reductases and isomerases when the virus infects a naive cell and traffics through the ER (9,11). One molecule of either minor capsid protein, VP2 or VP3, is associated with each pentamer and is concealed by VP1 from antibody detection until disassembly begins in the ER (12,13).…”