Non-enveloped virus infection probed with host cellular molecules : a structural study (2002)

<p>Early steps in virus replication require binding of the virus to its target cell, entry into the cell, and delivery of the viral genome into the cell in order to gain access to the cellular macromolecular synthesis machinery. This infectious process can only be initiated if the virus successfully attaches to a specific receptor on the plasma membrane of the target cell. Receptor specificity is one important factor for determining the target cell tropism of a virus.</p><p>Picornaviruses are a group of small non-enveloped viruses belonging to a well- characterized virus family. The prototypic picornavirus consists of a singlestranded positive-sense RNA molecule that is encased by a protein capsid approximately 50Å thick and 300Å in diameter. The capsid is composed of 60 copies of four virus proteins, arranged in a T=1 icosahedral lattice. The three larger proteins (VP1-3) form the outer surface and share a common eight-antiparallel-beta-barrel structural motif. The smallest viral protein (VP4) is located at the interface between the capsid protein and viral genomic RNA. The canyon, the surface depression around each of the twelve icosahedral fivefold axes, is the most dominant structural feature among the picornaviruses.</p><p>Although similarities in structure and sequence suggest that picornaviruses were derived from a common ancestor, they have evolved to use different cellular receptors for infection. For instance, the human rhinovirus major group viruses use intercellular adhesion molecule-1 (ICAM-1) while poliovirus uses the poliovirus receptor (PVR). These receptors belong to the immunoglobulin (Ig) superfamily and are composed of five and three Ig domains, respectively. Cryo-electron microscopy and image reconstruction analysis has revealed that while ICAM-1 and PVR bind to the canyon region of the virus, they bind in different orientations. Specifically, ICAM-1 stretches deeply into the canyon and interacts with the residues on the canyon floor. Importantly, the residues in the canyon rim region are hypervariable among rhinovirus serotypes, indicating that rhinoviruses mutate the exposed residues as a strategy to escape host immune surveillance. By comparison, PVR interacts with the exposed canyon rim region and partially covers the antigenic epitope of poliovirus. This may partially explain why poliovirus has only three serotypes while the rhinovirus major group has nearly 90 serotypes. A third prototypic picornavirus, echovirus 1, uses alpha2beta1 integrin as its cellular receptor. The binding of echovirus I to alpha2beta1 integrin has been mapped to the I-domain, a domain inserted into the alpha2 subunit. The I-domain, a globular shaped protein, was bound to the exposed canyon region of the virus. Presently, only two serotypes of echovirus are reported to bind to alpha2beta1 integrin. All picornaviruses studied to date recognize the binding receptor by means of complementary electrostatic interactions.</p><p>After binding to the specific cell surface receptor, picornaviruses are required to uncoat in order to release the viral genome into the target cell. Two uncoating intermediates of human rhinovirus serotype 3, containing different amounts of RNA, appeared after incubation with ICAM-1 at 37°C. The capsid underwent an expansion step to externalize the peptides, which is account for the density located at the region between the receptor-binding sites and viral fivefold plateau. This increased density could be due to externalized viral peptide. There was no density channel in the capsid but lower density was observed at the canyon region, suggesting the exit of internal components during uncoating.</p><h3>List of scientific papers</h3><p>I. Xing L, Kato K, Li T, Takeda N, Miyamura T, Hammar L, Cheng RH (1999). Recombinant hepatitis E capsid protein self-assembles into a dual-domain T = 1 particle presenting native virus epitopes. Virology. 265(1): 35-45. <br><a href="https://pubmed.ncbi.nlm.nih.gov/10603315">https://pubmed.ncbi.nlm.nih.gov/10603315</a><br><br></p><p>II. Xing L, Tjarnlund K, Lindqvist B, Kaplan GG, Feigelstock D, Cheng RH, Casasnovas JM (2000). Distinct cellular receptor interactions in poliovirus and rhinoviruses. EMBO J. 19(6): 1207-16. <br><a href="https://pubmed.ncbi.nlm.nih.gov/10716921">https://pubmed.ncbi.nlm.nih.gov/10716921</a><br><br></p><p>III. Forsell K, Xing L, Kozlovska T, Cheng RH, Garoff H (2000). Membrane proteins organize a symmetrical virus. EMBO J. 19(19): 5081-91. <br><a href="https://pubmed.ncbi.nlm.nih.gov/11013211">https://pubmed.ncbi.nlm.nih.gov/11013211</a><br><br></p><p>IV. Wu B, Hammar L, Xing L, Markarian S, Yan J, Iwasaki K, Fujiyoshi Y, Omura T, Cheng RH (2000). Phytoreovirus T = 1 core plays critical roles in organizing the outer capsid of T = 13 quasi-equivalence. Virology. 271(1): 18-25. <br><a href="https://pubmed.ncbi.nlm.nih.gov/10814566">https://pubmed.ncbi.nlm.nih.gov/10814566</a><br><br></p><p>V. Haag L, Garoff H, Xing L, Hammar L, Kan ST, Cheng RH (2002). Acid-induced movements in the glycoprotein shell of an alphavirus turn the spikes into membrane fusion mode. EMBO J. 21(17): 4402-10. <br><a href="https://pubmed.ncbi.nlm.nih.gov/12198142">https://pubmed.ncbi.nlm.nih.gov/12198142</a><br><br></p><p>VI. Xing L, Casasnovas J, Cheng RH (2002). Structures of human rhinovirus complex with intercellular adhesion molecule-1 uncover the dynamics of receptor-mediated virus uncoating. [Submitted]</p><p>VII. Xing L, Huhtala M, Pietiainen V, Kapyla J, Heino J, Johnson M, Hyypia T, Cheng RH (2002). The srtuctural basis of intergrin action as a virus receptor. [Submitted]</p>