We report the first atomic resolution structure of an animal virus, human rhinovirus 14. It is strikingly similar to known icosahedral plant RNA viruses. Four neutralizing immunogenic regions have been identified. These, and corresponding antigenic sequences of polio and foot-and-mouth disease viruses, reside on external protrusions. A large cleft on each icosahedral face is probably the host cell receptor binding site.

Although rhinovirus (RV) infections can cause asthma exacerbations and alter lower airway inflammation and physiology, it is unclear how important bronchial infection is to these processes. To study the kinetics, location, and frequency of RV appearance in lower airway tissues during an acute infection, immunohistochemistry and quantitative polymerase chain reaction analysis were used to analyze the presence of virus in cells from nasal lavage, sputum, bronchoalveolar lavage, bronchial brushings, and biopsy specimens from 19 subjects with an experimental RV serotype 16 (RV16) cold. RV was detected by polymerase chain reaction analysis on cells from nasal lavage and induced sputum samples from all subjects after RV16 inoculation, as well as in 5 of 19 bronchoalveolar lavage cell samples and in 5 of 18 bronchial biopsy specimens taken 4 days after virus inoculation. Immunohistochemistry detected RV16 in 39 and 36% of all biopsy and brushing samples taken 4 and 15 days, respectively, after inoculation. Infected cells were primarily distributed in discrete patches on the epithelium. These results confirm that infection of lower airway tissues is a frequent finding during a cold and further demonstrate a patchy distribution of infected cells, a pattern similar to that reported in upper airway tissues.

Rhinovirus (RV) infections can alter lower airway physiology and inflammation, yet the characteristics of RV replication in lower airway cells are incompletely understood. An RV serotype 16 (RV16)-specific monoclonal antibody was identified. Immunohistochemistry and an infectious center assay were used to quantitate the infectivity of RV16 in primary bronchial and adenoidal epithelial cells. The proportion of infectible epithelial cells increased with the inoculum but did not exceed 10%. Analysis of bronchial tissue samples infected ex vivo demonstrated a small subset of RV-infected cells in the epithelial layer. These data confirm previous reports that RV infects only a small subset of epithelial cells in upper airway tissues and indicate that lower airway epithelial cells have a similar susceptibility to RV infection. In confirming that RV can infect cells in the lower airway, these results suggest that lower airway dysfunction occurs through this mechanism in susceptible persons.

A collection of 35 mouse monoclonal antibodies, raised against human rhinovirus 14 (HRV-14), was used to isolate 62 neutralization-resistant mutants. When cross-tested against the antibodies in a neutralization assay, the mutants fell into four antigenic groups, here called neutralization immunogens: NIm-IA,-IB,-II, and-III. Sequencing the mutant RNA in segments corresponding to serotype-variable regions revealed that the amino acid substitutions segregated into clusters, which correlated exactly with the immunogenic groups (NIm-IA mutants at VP1 amino acid residue 91 or 95; NIm-Il mutants at VP2 residue 158, 159, 161, or 162; NIm-Ill mutants at VP3 residue 72, 75, or 78; and NIm-IB mutants at two sites, either VP1 residue 83 or 85, or residue 138 or 139). Examination of the three-dimensional structure of the virus (M.

Antigenic mutants of poliovirus (Sabin strain, serotype 1) were isolated by the resistance of the virus to anti-Sabin neutralizing monoclonal antibodies. The amino acid replacements within the capsid protein sequence causing the altered antigenicity were identified for each of 63 isolates. The mutations cluster into distinct nonoverlapping peptide segments that group into three general immunological phenotypes on the basis of cross-neutralization analyses with 15 neutralizing anti-Sabin monoclonal antibodies. Location of the mutated amino acid residues within the three-dimensional structure of the virion indicates that the majority of these amino acid residues are highly exposed and located within prominent structural features of the viral surface. Those mutated amino acid residues that are less accessible to antibody interaction are often involved in hydrogen bonds or salt bridges that would stabilize the local tertiary structure of the antigenic site. The interactions of the peptide segments that form these neutralizing sites suggest specific models for the generation of neutralization-resistant variants and for the interaction between the viral surface and antibody.