Virology and clinical textbooks and virtually all web-based information sources generally describe human rhinoviruses (HRVs) as the most frequent cause of the common cold. In this light, HRVs are important pathogens because common colds are so widespread and annoying, and from an economic perspective, supplying symptomatic-relief medications is a huge industry. A 2003 study estimated that expenditures on common cold medications in the United States exceeded 4 billion dollars, including 1.1 billion dollars spent on inappropriate prescriptions for antibiotics (18
). Finding a cure for the common cold has been a much-publicized goal ever since HRVs were first discovered in the 1950s and 1960s. The basic biology of the replication cycle was soon described, and most HRVs were found to replicate best at 33° to 35°C (88
), which is consistent with their role as upper airway pathogens. HRVs were found to have tremendous diversity, and approximately 100 serotypes in two groups (A and B) had been identified by 1990, when it was presumed that all, or nearly all, HRVs had been identified. These HRVs were found to bind to one of two main receptors: ICAM-1 (major group) (30
) and the low-density-lipoprotein receptor (most of the minor group) (35
). Despite advances in understanding HRV genetics and the picornavirus replication cycle, efforts toward developing specific antivirals have fallen short due to modest efficacy, side effects, drug interactions, and economic considerations (16
). Consequently, enthusiasm for pursuing a common cold cure has waned, and the pharmaceutical industry has refocused attention on viruses that cause more-significant illnesses. This failure is a bit embarrassing. As summarized by White and Fenner, “In this era of organ transplantation, genetic engineering, and other dramatic demonstrations of the wonders of medical science, the man in the street perceives a certain irony in the inability of modern medicine to make the slightest impact on that most trivial of all human ailments, the common cold” (119
In addition to relaying a sense of irony, this statement also sums up an opinion held by many that HRV infection causes a trivial illness, and among viruses, HRV is afforded little respect by clinicians and even by many virologists. However, this opinion may be based on incomplete information and some historic assumptions about HRV that have since been disproven. In fact, there is now convincing evidence that HRVs (i) can replicate in the lower airways, (ii) play a critical role in causing exacerbations of asthma and other chronic lung diseases, (iii) can cause bronchiolitis and pneumonia, and (iv) are a common cause of hospitalization. In addition, since the discovery of a unique HRV strain in 2006, over 50 additional strains of HRV have been identified, the majority of which are members of the newly designated HRV-C species, with distinct biologic features, including receptor specificity. In this review, recent information concerning the role of HRVs as important respiratory pathogens, especially related to asthma and lower airway illnesses, will be discussed.