Studies based on the above considerations should focus on processes that initiate MS years or a decade before manifestation of the disease. Subsequently, a better understanding of the highly complex immunopathology of MS will, hopefully, lead to the eventual development of vaccination strategies for the prevention or correction of anomalies in immune function. Such vaccines could well work by preventing or correcting hygiene-related immune dysregulation [64] . It has previously been postulated that a vaccine based on EBV should afford a high level of protection against MS [16] , but the exact nature of an efficient and safe vaccine would depend on the nature of the relationship between EBV and MS. If the framework presented in this study is in principle confirmed, the appropriate vaccine is most likely to be a living attenuated one that induces a strong T cell response to EBV epitopes but is not expressing EBV EBNA1 in latency. Evidence of Recombination and Genetic Diversity in Human Rhinoviruses in Children with Acute Respiratory Infection BACKGROUND: Human rhinoviruses (HRVs) are a highly prevalent cause of acute respiratory infection in children. They are classified into at least three species, HRV-A, HRV-B and HRV-C, which are characterized by sequencing the 5′ untranslated region (UTR) or the VP4/VP2 region of the genome. Given the increased interest for novel HRV strain identification and their worldwide distribution, we have carried out clinical and molecular diagnosis of HRV strains in a 2-year study of children with acute respiratory infection visiting one district hospital in Shanghai. METHODOLOGY/FINDINGS: We cloned and sequenced a 924-nt fragment that covered part of the 5′UTR and the VP4/VP2 capsid genes. Sixty-four HRV-infected outpatients were diagnosed amongst 827 children with acute low respiratory tract infection. Two samples were co-infected with HRV-A and HRV-B or HRV-C. By comparative analysis of the VP4/VP2 sequences of the 66 HRVs, we showed a high diversity of strains in HRV-A and HRV-B species, and a prevalence of 51.5% of strains that belonged to the recently identified HRV-C species. When analyzing a fragment of the 5′ UTR, we characterized at least two subspecies of HRV-C: HRV-Cc, which clustered differently from HRV-A and HRV-B, and HRV-Ca, which resulted from previous recombination in this region with sequences related to HRV-A. The full-length sequence of one strain of each HRV-Ca and HRV-Cc subspecies was obtained for comparative analysis. We confirmed the close relationship of their structural proteins but showed apparent additional recombination events in the 2A gene and 3′UTR of the HRV-Ca strain. Double or triple infections with HRV-C and respiratory syncytial virus and/or bocavirus were diagnosed in 33.3% of the HRV-infected patients, but no correlation with severity of clinical outcome was observed. CONCLUSION: Our study showed a high diversity of HRV strains that cause bronchitis and pneumonia in children. A predominance of HRV-C over HRV-A and HRV-B was observed, and two subspecies of HRV-C were identified, the diversity of which seemed to be related to recombination with former HRV-A strains. None of the HRV-C strains appeared to have a higher clinical impact than HRV-A or HRV-B on respiratory compromise. Human rhinoviruses (HRVs) are a highly p revalent cause of the acute respiratory infection (ARI) defined as the common cold [1, 2, 3] , which is frequently associated in children with bronchitis, bronchiolitis, wheezing, pneumonia, asthma and otitis [4, 5, 6, 7, 8, 9] . HRVs are classified in genus Enterovirus (HEVs) in family Picornaviridae [10] . HRVs are non-enveloped, single-stranded, positive-sense RNA viruses of approximately 7200 nt, composed of a 59 untranslated region (UTR), followed by a long open reading frame coding for capsid proteins VP4, VP2, VP3 and VP1, and seven non-structural proteins 2A, 2B, 2C, 3A, 3B, 3C and 3D, and terminated by a short 39UTR and poly A tract.