Human rhinoviruses (HRVs) cause the common cold and often induce lower airway symptoms such as cough and wheezing. Although HRV infection is presumed to involve primarily ciliated epithelial cells, this has not been confirmed in vivo, and the cellular distribution and spread of infection as well as the pathogenesis of cold related nasal and chest symptoms remain speculative. We have developed in situ hybridization (ISH) to explore localization of the virus to airway tissues, employing HRV 16-derived oligonucleotide probes after sequencing part of the genome of this serotype. A reverse transcription-polymerase chain reaction was used to generate DNA from HRV 16 for sequencing; this yielded 305 nucleotide bases that showed considerable homology to other HRVs. The HRV 16 sequence was used to design oligonucleotides functioning as antisense and sense probes. These probes as well as random sequence and pathogen control oligonucleotides were applied to HRV-infected cell-clot complexes and finally to sections fr...