Affiliation:
1. Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710
Abstract
ABSTRACT
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.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Cited by
5 articles.
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