Human metapneumovirus: Investigation of epidemiology strain diversity and human immune response

Human metapneumovirus (hMPV) is a newly described respiratory virus belonging to the Paramyxoviridae family, first identified in respiratory samples of ·children with acute respiratory tract infection (ARTI). Since its discovery hMPV has been associated with ARTI worldwide, however, important questions remain as to the contribution ofhMPV to respiratory illness, and its impact on public health. Extensive surveillance ofhMPV within different populations of the United Kingdom (UK) demonstrates it is an important cause of ART! in the elderly, and influenza like illness ~ (ILl) in people of all ages in the community. Furthermore it is a frequent cause of hospitalisation in young children. Recombinant baculovirus expressed hMPV nucleocapsid protein (N) proved to be a useful source of antigen for the development of an hMPV specific ELISA. Analysis of age stratified sera from the UK indicates that a majority of children are infected by the age of 6 years with primary infections occurring throughout infancy. Virtually all adults have detectable levels ofhMPV antibody; however, reinfection with hMPV is common, raising questions concerning acquisition and duration of immunity. Sequence analysis of the attachment glycoprotein (0), shows a high degree of nucleotide and amino acid variation and extensive glycosylation. Frequent nucleotide insertions or deletions result in frame shift mutations which can drastically alter the appearance of the protein and often results in premature termination. Antibody recognition of hMPV 0 is likely to be highly strain specific and dependent on the extent of glycosylation, suggesting an involvement of 0 in immune evasion. Phylogenetic analysis of hMPV 0 gene sequence shows that whilst a large degree of variation exists within this gene, strains circulating within the UK are genetically similar to strains circulating elsewhere in the world, and similar strains circulate throughout different years and populations within the UK.EThOS - Electronic Theses Online ServiceGBUnited Kingdo