Work

Cellular integrins function as entry receptors for human cytomegalovirus via a highly conserved disintegrin-like domain

Year: 2004

Type: article

Abstract: Human cytomegalovirus (HCMV) is capable of manifesting disease in nearly every organ system in immunocompromised patients. This broad pathogenic tropism correlates with the ability of the virus to infect all tested vertebrate cell types in vitro, a characteristic that has made receptor identification extremely difficult. During virus entry, HCMV induces cellular morphological changes and signaling cascades consistent with engagement of cellular integrins; however, HCMV structural proteins do not possess the widely used RGD integrin-binding motif. We identified an integrin-binding disintegrin-like domain within HCMV envelope glycoprotein B, a protein required for virus entry and fusion throughout the Herpesviridae. Accepted receptor criteria are met through the use of function-blocking integrin Abs, beta1 integrin knockout mouse fibroblasts, and glycoprotein B disintegrin-like peptides, all of which support a critical role for alpha2beta1, alpha6beta1, and alphaVbeta3 integrins as HCMV entry receptors and signaling mediators acting during the penetration stage of the entry pathway. Strikingly, the glycoprotein B disintegrin-like domain is conserved in many human and animal herpesviruses, suggesting that integrins may support entry across this medically important virus family.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.0406821101

Authors: Adam L. Feire, Heidi Koss, Teresa Compton

Institutions: University of Wisconsin–Madison, Northwestern University

Language: English

Topic: Cytomegalovirus and herpesvirus research

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: U.S. Public Health Service