The maximal similarity between predicted HIV antigens (x) and the set of human 230,460 self-antigens (y) was defined as the selfsimilarity score S self (x) = max(S(x,y)) for HIV peptide x. Self-similarity scores were obtained for all confirmed HIV epitopes and putative HIV antigens. Because no identical matches were found between HIV epitopes and self-antigens, self-similarity scores were always S(x,y),1. Confirmed HIV epitopes and putative non-immunogenic HIV peptides were ranked on maximum self-similarity, and the combined ranking was split in two parts: a) The peptides with a selfsimilarity score greater than 0.85 and b) and peptide with a selfsimilarity score below 0.85. We used Fisher's exact test to compute the significance of the difference in the frequency of putative HIV epitopes in the top versus the bottom. Distinguishing Molecular Features and Clinical Characteristics of a Putative New Rhinovirus Species, Human Rhinovirus C (HRV C) BACKGROUND: Human rhinoviruses (HRVs) are the most frequently detected pathogens in acute respiratory tract infections (ARTIs) and yet little is known about the prevalence, recurrence, structure and clinical impact of individual members. During 2007, the complete coding sequences of six previously unknown and highly divergent HRV strains were reported. To catalogue the molecular and clinical features distinguishing the divergent HRV strains, we undertook, for the first time, in silico analyses of all available polyprotein sequences and performed retrospective reviews of the medical records of cases in which variants of the prototype strain, HRV-QPM, had been detected. METHODOLOGY/PRINCIPLE FINDINGS: Genomic analyses revealed that the six divergent strains, residing within a clade we previously called HRV A2, had the shortest polyprotein of all picornaviruses investigated. Structure-based amino acid alignments identified conserved motifs shared among members of the genus Rhinovirus as well as substantive deletions and insertions unique to the divergent strains. Deletions mostly affected regions encoding proteins traditionally involved in antigenicity and serving as HRV and HEV receptor footprints. Because the HRV A2 strains cannot yet be cultured, we created homology models of predicted HRV-QPM structural proteins. In silico comparisons confirmed that HRV-QPM was most closely related to the major group HRVs. HRV-QPM was most frequently detected in infants with expiratory wheezing or persistent cough who had been admitted to hospital and required supplemental oxygen. It was the only virus detected in 65% of positive individuals. These observations contributed to an objective clinical impact ranging from mild to severe. CONCLUSIONS: The divergent strains did not meet classification requirements for any existing species of the genus Rhinovirus or Enterovirus. HRV A2 strains should be partitioned into at least one new species, putatively called Human rhinovirus C, populated by members detected with high frequency, from individuals with respiratory symptoms requiring hospital admission. Human rhinoviruses (HRVs) are the most frequently detected pathogens in acute respiratory tract infections (ARTIs). HRVs have been associated with lower respiratory tract (LRT) illness and more serious clinical outcomes within pediatric and other vulnerable populations [1] . Despite this, HRV strains continue to be commonly defined, en masse, by their most prolific and currently most well-defined role in causing the 'common cold' [2, 3] .