Phylogenetic analysis of MPV genes consistently identifies four genetic clades, two major groups designated A and B, each with two minor groups designated A1, A2, B1, and B2 [180, 198C203]. among human paramyxoviruses in that the attachment protein does not contribute to protective antibodies. Further, the G protein exhibits a high degree of genetic variability between subgroups, with as low as 29 % amino acid identity between the major A and B subgroups and a minimum 60 %60 % identity within subgroups [202, 215C218]. The selective GLYX-13 (Rapastinel) pressure for this diversity is unclear. In contrast to G, the F protein is usually conserved, with a minimum 94 % amino acid identity between A and B subgroups and a minimum 98 % identity within subgroups [179, 202, 203]. Presumably you will find functional constraints around the diversity of F, since the mutation rate of MPV is usually high, much like other RNA viruses. The major question regarding the diversity between major or minor subgroups is usually whether it contributes to antigenic variance or escape in human populations. Cross-neutralization against heterologous computer virus from your A and B lineages was tested using experimental contamination of ferrets [202]. This study found relative neutralization of homologous to heterologous computer virus ranging from 12 to 96-fold difference, thus providing some evidence for antigenic serotypes. However, subsequent experiments using hamsters, African green monkeys, chimpanzees, and rhesus macaques found that the A and B groups were 64C99 % related antigenically [219]. Infected animals developed neutralizing antibodies that were highly effective against heterologous computer virus, and previously infected primates were guarded against challenge with heterologous computer virus. IL-16 antibody Cynomolgus macaques infected with A or B subgroup viruses or with candidate vaccines exhibited only a 6C16-fold difference in neutralizing titer against homologous and heterologous viruses [220, 221]. Taken together, these data show that while MPV F exhibits some antigenic diversity, the GLYX-13 (Rapastinel) computer virus does not have truly unique serotypes. The potential implications for human epidemiology are discussed further below. Descriptive Epidemiology Incidence GLYX-13 (Rapastinel) and Prevalence Data Numerous studies document the fact that MPV contamination is ubiquitous and that reinfection is usually common. Serosurveys screening large sample selections in Canada, China, Croatia, Germany, Israel, Japan, the Netherlands, Taiwan, Thailand, the USA, and Uruguay show that 95C100 % of children have antibodies against MPV by the age of 5 years [222C231]. In many of these studies, 50C75 % of children are seropositive by age 2 years, suggesting that most acquire main MPV contamination early. Most identify a decrease in serum MPV antibody titer from birth to 6C12 months, presumably due to the expected decline of maternally derived antibodies. Studies in Japan and India that compared MPV and RSV titers in the same cohort found that after the expected nadir during early infancy, RSV titers began increasing at an earlier age than MPV [232, 233]. This obtaining is usually interesting in light of epidemiologic data suggesting that main MPV contamination peaks between 6 and 12 months of life compared with the peak of RSV at 2C3 months (discussed GLYX-13 (Rapastinel) below). Longitudinal studies in adults and children have documented reinfection by a fourfold rise in serum antibody titer [222, 230, 231, 234C237]. Risk of Contamination and Reinfection The serological data show that MPV contamination is nearly ubiquitous during the first years of life. Further, reinfection occurs throughout life. In children, main MPV contamination is usually associated generally with lower respiratory illness, while reinfection is usually associated with upper tract disease [182, 238]. Risk of Severe Lower Respiratory Contamination (LRI) During Infancy Most epidemiologic studies of MPV in children show that this computer virus is the second leading cause of lower respiratory contamination after RSV. The prevalence of MPV in studies of children with LRI is usually 5C25 %. A 25-12 months prospective study of normally healthy.