Overview of research interests
Members of the subfamily Pneumovirinae of the family Paramyxoviridae, given the collective name pneumoviruses, are responsible for acute respiratory infections in their hosts. The subfamily is divided into two genera on the basis of differences in genome organisation. The genus pneumovirus contains two members, the respiratory syncytial viruses, of which there are strains which infect humans (RSV), cattle (bovine RSV; BRSV) and goats (caprine RSV), and PVM which infects a wide range of rodents and other animals, including man. RSV is the major cause of hospitalisation of children less than one year of age with respiratory infection worldwide. BRSV is a common infection in cattle which, though not generally life-threatening, is of economic importance. Avian pneumovirus (APV) which has been assigned to a separate genus, the metapneumoviruses, is a significant cause of respiratory disease in domestic poultry, especially turkeys, in which it is of major economic significance. The most recently described pneumovirus, human metapneumovirus (hMPV), is a major respiratory pathogen second in importance to RSV and has a genome organisation similar to that of APV.
The RSV and PVM genomes are single negative sense RNA molecules of approximately 15kb in length. The APV and hMPV genomes are smaller, at approximately 13kb. Replication and transcription of the virus genome occurs in the cytoplasm of the infected cell using virus-encoded proteins. While the minimal RNA polymerase requirements of the pneumoviruses are the ribonucleoprotein (RNA complexed with nucleoprotein, N), the phosphoprotein, P, and the large protein, L, transcription is greatly enhanced by the presence of a further viral protein, M2. The M2 gene is unique to the Pneumovirinae and no similarity with any known transcription factor has been described.
Recently, we have described a novel form of translational regulation, coupled translation, where the expression of a second ORF in a mRNA requires prior translation of the upstream ORF. This phenomenon has been shown to occur in all pneumoviruses, though the degree of coupling varies.