Human respiratory syncytial virus (HRSV) causes substantial morbidity and mortality in vulnerable patients, such as the very young, the elderly, and immunocompromised individuals of any age. ...Nosocomial transmission of HRSV remains a serious challenge in hospital settings, with intervention strategies largely limited to infection control measures, including isolation of cases, high standards of hand hygiene, cohort nursing, and use of personal protective equipment. No vaccines against HRSV are currently available, and treatment options are largely supportive care and expensive monoclonal antibody or antiviral therapy. The limitations of current animal models for HRSV infection impede the development of new preventive and therapeutic agents, and the assessment of their potential for limiting HRSV transmission, in particular in nosocomial settings. Here, we demonstrate the efficient transmission of HRSV from immunocompromised ferrets to both immunocompromised and immunocompetent contact ferrets, with pathological findings reproducing HRSV pathology in humans. The immunocompromised ferret-HRSV model represents a novel tool for the evaluation of intervention strategies against nosocomial transmission of HRSV.
RNA replication of dengue virus (DENV) requires an RNA-RNA mediated circularization of the viral genome, which includes at least three sets of complementary RNA sequences on both ends of the genome. ...The 5\' and the 3\' untranslated regions form several additional RNA elements that are involved in regulation of translation and required for RNA replication. Communication between the genomic termini results in a structural reorganization of the RNA elements, forming a functional RNA panhandle structure. Here we report that the sequence composition downstream of the 5\' CS element in the capsid gene, designated as downstream CS (dCS) sequence - but not the capsid protein - also influences the ability of the viral genome to circularize and hence replicate by modulating the topology of the 5\' end. These results provide insights for the design of reporter sub-genomic and genomic mosquito-borne flavivirus constructs and contribute to the understanding of viral RNA replication.
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