Pneumoviruses: Molecular Genetics and Reverse Genetics

78 Abstract Pneumoviruses are responsible for significant respiratory disease in their hosts and represent a major problem for human and animal health. Pneumoviruses are members of the family Paramyxoviridae, subfamily Pneumovirinae and the virus particles consist of a negative-sense, nonsegmented RNA genome within a helical nucleocapsid structure enveloped in a lipid membrane derived from the host cell. Over the past four decades much work has extended our understanding of the molecular biology and pathogenesis of pneumoviruses but despite this only limited treatments and prophylaxis are available. The human pathogen, respiratory syncytial virus (hRSV) which belongs to the genus of Pneumovirus is the best characterized of the subfamily. HRSV is the major cause of hospitalisation of very young children with respiratory disease worldwide. No vaccine is available though new treatments offer some respite for children in the highest risk groups, the immunocompromised and children with congenital heart disease. The recently discovered human pathogen human metapneumovirus (hMPV) belongs to the genus Metapneumovirus and recent data indicates that this virus is second only to hRSV in terms of disease impact. The pneumoviruses also include agents of veterinary importance such as bovine respiratory syncytial virus (bRSV), ovine and caprine RSV, and pneumonia virus of mice (PVM: all in the genus Pneumovirus) and avian metapneumovirus (APV: genus Metapneumovirus). The development of reverse genetics systems for negative strand RNA viruses has opened the possibility of manipulating the virus genomes to identify genes involved in pathogenesis and to explore the biological consequences of specific mutations. This information is informing the rational design of new vaccines. These plasmid-based systems have shown that for all paramyxoviruses the N, P and L proteins are necessary and sufficient for RNA replication. However, the pneumoviruses differ from the other family members in that fully efficient transcription from the virus genome requires the presence of an additional protein encoded by the M2 gene. The present article reviews pneumovirus biology and molecular genetics including a discussion of current concepts of Pneumovirus reverse genetics.