| Rhinoviruses (RVs) are plus-sense, single-stranded RNA viruses in the family Picornaviridae that are causative agents of the majority of upper respiratory tract infections, or "common colds," in humans. RVs infect both the upper and lower respiratory tract, and in addition to the common cold may also cause pneumonia in infants and the elderly, complications in cystic fibrosis patients, and asthma exacerbations. Despite the medical importance of human rhinoviruses, the pathogenesis of rhinovirus-induced illness is poorly understood. An animal model to study rhinovirus pathogenesis would greatly augment efforts to study possible means of preventing or treating RV infections. The major group rhinovirus serotypes bind human intercellular adhesion molecule-1 (ICAM1) for cell entry. While mice also express a homolog of ICAM-1, it is not sufficiently similar to the human ICAM-1 to bind major group RVs. A transgenic mouse expressing human ICAM-1 was developed and infected with mouse-adapted RV16/L and RV39/L. Because the human ICAM-1 transgene was not expressed on the cell surface, however, these mice were not susceptible to infection. The minor group rhinovirus serotypes bind the low-density lipoprotein receptor (LDLR) for cell entry, and can bind mouse LDLR. However, as with the major group serotypes, a post-entry block to replication has been observed in mouse cells. By serial passage through mouse embryonic fibroblasts and mouse lung epithelial cells, variants of RV1A that replicate in mouse cells were selected. The adaptation to growth in mouse cells was mediated by amino acid changes in the 3A non-structural protein. Following chemical permeabilization of the airway, mouse cell-adapted RV1A was capable of infecting mice and producing DC responses to infection in vivo. The availability of a mouse model for RV infection and pathogenesis will permit detailed studies on RV pathogenesis and may identify targets for therapeutic intervention. |
