Interaction between three picornaviruses and their common receptor, ICAM-1

Chuan Xiao, Purdue University

Abstract

Coxackievirus A21 (CVA21) and human rhinoviruses (HRVs) are causative pathogens of the common cold. In the family of Picornaviridae , CVA21 and polioviruses belong to the Enterovirus genus, whereas rhinoviruses comprise a distinct genus. Nevertheless, CVA21 and major group HRV serotypes including 14 and 16 recognize intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, whereas polioviruses recognize poliovirus receptor (PVR). ICAM-1 is a cell surface glycoprotein that provides adhesion between leukocytes and endothelial cells. A variant of ICAM-1, ICAM-1Kilifi, cannot form a stable complex with HRV16 but still binds to CVA21 and HRV14. X-ray crystallography and cryo-electron microscope (cryo-EM) image analysis were combined to study the complex structures between ICAM-1 and each of the three viruses, CVA21, HRV14 and HRV16. The crystal structure of CVA21 was determined to 3.2 Å resolution. Three-dimensional structures of CVA21 complexed with ICAM-1Kilifi, of HRV14 and HRV16 each complexed with ICAM-1, and of HRV14 complexed with ICAM-1Kilifi, were determined by cryo-EM image reconstruction to between 8 and 13 Å resolution. The cryo-EM maps were fitted with the crystal structures of ICAM-1 and the corresponding viruses. The binding site of ICAM-1 to CVA21 or HRVs, and that of PVR to polioviruses overlap at the canyon region. Interactions within this common region may be essential for triggering viral destabilization after attachment to susceptible cells. However, the orientation of the receptor molecule relative to the virus surface is different for each virus. Significant differences in the structure of CVA21 with respect to the polioviruses account for the inability of ICAM-1 to bind polioviruses. Many virus/receptor contact residues are conserved within CVAs or HRVs but not between CVAs and HRVs, indicating that these two groups of viruses evolved separately to exploit different recognition modes of ICAM-1. Nevertheless, interfaces between the viruses and ICAM-1 display considerable shape and electrostatic complementarity and contain extensive ionic networks. The interactions between the viruses and ICAM-1Kilifi include one less salt bridge than with ICAM-1. As HRV16 has fewer overall interactions with ICAM-1 than HRV14, the absence of this salt bridge will have a greater impact on the binding of ICAM-1Kilifi to HRV16 than to HRV14.

Degree

Ph.D.

Advisors

Rossman, Purdue University.

Subject Area

Molecular biology|Microbiology|Biophysics

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