Adaptation of an ICAM-1-tropic enterovirus to the mouse respiratory tract.

Published

Journal Article

Respiratory tract (RT) infections by members of the enterovirus (EV) genus of the Picornaviridae family are the most frequent cause for the common cold and a major factor in the exacerbation of chronic pulmonary diseases. The lack of a practical small-animal model for these infections has obstructed insight into pathogenic mechanisms of the common cold and their role in chronic RT illness and has hampered preclinical evaluation of antiviral strategies. Despite significant efforts, it has been difficult to devise rodent models that exhibit viral replication in the RT. This is due mainly to well-known intracellular host restrictions of EVs with RT tropism in rodent cells. We report the evolution of variants of the common-cold-causing coxsackievirus A21, an EV with tropism for the human intercellular adhesion molecule 1 (hICAM-1), through serial passage in the lungs of mice transgenic for the hICAM-1 gene. This process was accompanied by multiple changes in the viral genome, suggesting exquisite adaptation of hICAM-1-tropic enteroviruses to the specific growth conditions within the RT. In vivo mouse RT-adapted, variant coxsackievirus A21 exhibited replication competence in the lungs of hICAM-1 transgenic mice, providing a basis for unraveling EV-host interactions in the mouse RT.

Full Text

Duke Authors

Cited Authors

  • Wang, ES; Dobrikova, E; Goetz, C; Dufresne, AT; Gromeier, M

Published Date

  • June 2011

Published In

Volume / Issue

  • 85 / 11

Start / End Page

  • 5606 - 5617

PubMed ID

  • 21450825

Pubmed Central ID

  • 21450825

Electronic International Standard Serial Number (EISSN)

  • 1098-5514

Digital Object Identifier (DOI)

  • 10.1128/JVI.01502-10

Language

  • eng

Conference Location

  • United States