Structure of murine polyomavirus complexed with an oligosaccharide receptor fragment

Abstract

The polyomaviruses are non-enveloped, icosahedrally symmetrical particles with circular double-stranded DNA genomes. The outer shell of the virion contains 360 copies of viral protein VP1 (M(r) approximately 42K) arranged in pentamers. We report here the structure at 3.65 A resolution of murine polyomavirus ('polyoma') complexed with an oligosaccharide receptor fragment. This structure has been determined using the previously described model of simian virus 40 (SV40). Although very similar in structure to SV40, polyoma has interesting biological differences. Cell-surface N-acetyl neuraminic acid (sialic acid) is required for polyoma infectivity, but not for SV40. Polyoma attaches to the surface of susceptible cells by stereospecific recognition of oligosaccharides terminating in (alpha 2,3)-linked sialic acid. Studies of pathogenicity show that the specificity of viral binding to such oligosaccharides is an important determinant of the virus' ability to establish a disseminated infection and to induce tumours in the natural host. The complex described here show how polyoma recognizes the receptor fragment and how strains with different receptor specificities can distinguish between alternative ligands. The results also suggest an explanation for the large disparity in pathogenicity exhibited by strains differing in only one amino-acid residue of VP1.

Mutations in the BC‐loop of the BKV VP1 region do not influence viral load in renal transplant patients

“…Analysis of 38 German BKV sequences from GenBank confirmed this observation (63.16%). In addition to the subtype classification, the polyomavirus VP1 protein determines the specificity and affinity for the cellular receptor [Stehle et al, 1994;Dugan et al, 2005;Dugan et al, 2007]. The VP1 surface is formed by three external loops: the BC-, DE-, and HIloop.…”

“…However, this difference did not reach statistical significance. Single amino acids within the BC-loop of polyomaviruses have been identified to be crucial for the interaction of the viral particle with the sialic acid residue of the cellular receptor [Stehle et al, 1994;Dugan et al, 2005;Gee et al, 2006]. In this study, we analyzed the amino acid sequence of the VP1 region in BKV isolates derived from renal transplant patients.…”

“…The virus replication is influenced by the ability of the viral particle to attach to and enter the target cell. The major capsid protein VP1 is responsible for the interaction of polyomaviruses with the host cell [Freund et al, 1991;Stehle et al, 1994].…”

Use of the baculovirus system to assemble polyomavirus capsid-like particles with different polyomavirus structural proteins: analysis of the recombinant assembled capsid-like particles.

“…This protein possesses the receptor-binding domain Stehle et al, 1994), a nuclear localization signal domain, a DNA-binding domain and a calcium-ion-binding domain Haynes et al, 1993 ;Moreland et al, 1991), which makes it crucial in virus attachment and virion assembly. When expressed in the bacterial system, polyomavirus VP1 could assemble into empty capsid-like structures spontaneously in the presence of calcium ions, with a size and morphology similar to those of the native polyomavirus capsids (Leavitt et al, 1985 ;Salunke et al, 1986 ;Haynes et al, 1993).…”

Replication and Assembly of Human Papillomaviruses

“…These protrusions are morphologically similar to the C-terminal "arm-invading" model of polyomaviruses, which reinforce the invading arms via an interpentameric disulfide bridge(s) (Baker et al, 1989(Baker et al, , 1991Stehle et al, 1994Stehle et al, , 1996Sapp et al, 1998;Jao et al, 1999). While detailed information regarding the intra-and interpentameric molecular interactions between pentamers cannot be garnered from the current atomic structure of HPV16, assumptions can be made from this model.…”