title: Adaptation of an ICAM-1-tropic enterovirus to the mouse respiratory tract.
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.
authors: Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors: Eric S
authors: ES
authors: Wang
authors: Elena
authors: E
authors: Dobrikova
authors: Christian
authors: C
authors: Goetz
authors: Andrew T
authors: AT
authors: Dufresne
authors: Matthias
authors: M
authors: Gromeier
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D004770:Enterovirus / Q000472:pathogenicity / Q000502:physiology*; D016679:Genome, Viral; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D012367:RNA, Viral / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D012137:Respiratory System / Q000821:virology*; D056189:Viral Tropism
chemical_list: D012367:RNA, Viral; D011991:Receptors, Virus; D018799:Intercellular Adhesion Molecule-1