Article

Ganglioside GT1b is a putative host cell receptor for the Merkel cell polyomavirus

Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, 347 UCB, Boulder, CO 80309, USA.
Journal of Virology (Impact Factor: 4.65). 08/2009; 83(19):10275-9. DOI: 10.1128/JVI.00949-09
Source: PubMed

ABSTRACT The Merkel cell polyomavirus (MCPyV) was identified recently in human Merkel cell carcinomas, an aggressive neuroendocrine skin cancer. Here, we identify a putative host cell receptor for MCPyV. We found that recombinant MCPyV VP1 pentameric capsomeres both hemagglutinated sheep red blood cells and interacted with ganglioside GT1b in a sucrose gradient flotation assay. Structural differences between the analyzed gangliosides suggest that MCPyV VP1 likely interacts with sialic acids on both branches of the GT1b carbohydrate chain. Identification of a potential host cell receptor for MCPyV will aid in the elucidation of its entry mechanism and pathophysiology.

Download full-text

Full-text

Available from: Kimberly D. Erickson, Oct 13, 2014
0 Followers
 · 
99 Views
  • Source
    • "A possible explanation for the broad migration profile is that the viral DNA is protected within virions that are heterogeneously complexed with relatively buoyant compounds , such as skin-derived lipids or cosmetics. This concept is consistent with recent observations showing that recombinant MCV VP1 capsomers can bind buoyant glycosphingolipids in the setting of sucrose gradients (Erickson et al., 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mounting evidence indicates that Merkel cell polyomavirus (MCV), a circular double-stranded DNA virus, is a causal factor underlying a highly lethal form of skin cancer known as Merkel cell carcinoma. To explore the possibility that MCV and other polyomaviruses commonly inhabit healthy human skin, we developed an improved rolling circle amplification (RCA) technique to isolate circular DNA viral genomes from human skin swabs. Complete MCV genomes were recovered from 40% of healthy adult volunteers tested, providing full-length, apparently wild-type cloned MCV genomes. RCA analysis also identified two previously unknown polyomavirus species that we name human polyomavirus-6 (HPyV6) and HPyV7. Biochemical experiments show that polyomavirus DNA is shed from the skin in the form of assembled virions. A pilot serological study indicates that infection or coinfection with these three skin-tropic polyomaviruses is very common. Thus, at least three polyomavirus species are constituents of the human skin microbiome.
    Cell host & microbe 06/2010; 7(6):509-15. DOI:10.1016/j.chom.2010.05.006 · 12.19 Impact Factor
  • Source
    • "However, it is generally thought that polyomaviruses are internalized by the interaction of VP1 with specific cellular receptors and co-receptors. It is known that BKV uses gangliosides GD1b and GT1b (Low et al., 2006); JCV uses GT1b and the serotonin receptor, 5HT2AR (Elphick et al., 2004); and GT1b has been proposed as a putative host cell receptor for MCV (Erickson et al., 2009). Virus then traffics through caveolae and the endoplasmic reticulum to the nucleus, where it is uncoated and the early message is transcribed. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Over 50 years of polyomavirus research has produced a wealth of insights into not only general biologic processes in mammalian cells, but also, how conditions can be altered and signaling systems tweaked to produce transformation phenotypes. In the past few years three new members (KIV, WUV, and MCV) have joined two previously known (JCV and BKV) human polyomaviruses. In this review, we present updated information on general virologic features of these polyomaviruses in their natural host, concentrating on the association of MCV with human Merkel cell carcinoma. We further present a discussion on advances made in SV40 as the prototypic model, which has and will continue to inform our understanding about viruses and cancer.
    Advances in Cancer Research 01/2010; 106:1-51. DOI:10.1016/S0065-230X(10)06001-X · 4.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The non-enveloped murine polyomavirus (Py) binds to receptors on the cell surface to gain entry into host cells. The virus then traffics to the endoplasmic reticulum (ER) where it penetrates the membrane and enters the cytosol, finally reaching the nucleus to cause infection. How Py is transported from the plasma membrane to the ER, however, is not clear. The sialic acid-galactose containing gangsliosides GD1a and GT1b have been reported to be the functional receptors for Py to stimulate Py infection in host cells. Many glycoproteins, which also contain terminal sialic acid-galactose moiety, can in principle engage Py to be Py’s receptors. However, how these glycolipid and glycoprotein receptors guide Py intracellular transport and regulate Py infection are poorly understood. We show that GD1a is the functional entry receptor for Py. GD1a binds to Py on the plasma membrane, and the GD1a-Py complex is internalized and transported to the endolysosomes where the low pH triggers a conformational change that promotes the subsequent ER-to-cytosol membrane penetration of Py. GD1a then sorts Py from the endolysosomes to the ER, leading Py to the infectious pathway. By contrast, glycoproteins act as decoy receptors. They compete with GD1a on the cell surface and interact with Py, guiding Py to the endolysosomes where the virus is trapped and infection is restricted. Therefore, glycolipids and glycoproteins, two major constituents of the plasma membrane, act in opposing manners to control Py infection.
Show more