Pneumoviruses: Molecular Genetics and Reverse Genetics

Pneumoviruses are responsible for significant respiratory disease in their hosts and represent a major problemfor human and animal health. Pneumoviruses are members of the family Paramyxoviridae, subfamilyPneumovirinae 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 fourdecades 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 thesubfamily. 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 riskgroups, the immunocompromised and children with congenital heart disease. The recently discoveredhuman pathogen human metapneumovirus (hMPV) belongs to the genus Metapneumovirus and recentdata indicates that this virus is second only to hRSV in terms of disease impact. The pneumoviruses alsoinclude agents of veterinary importance such as bovine respiratory syncytial virus (bRSV), ovine andcaprine 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 RNAviruses 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 differfrom the other family members in that fully efficient transcription from the virus genome requires the presenceof an additional protein encoded by the M2 gene. The present article reviews pneumovirus biology andmolecular genetics including a discussion of current concepts of Pneumovirus reverse genetics.