Measles is a highly contagious disease that most commonly strikes children. The causative agent, measles virus (MV), is generally transmitted by aerosolized secretions deposited on upper-respiratory-tract mucosal surfaces. Exposure leads to local respiratory tract replication; infection of regional lymphoid tissues then occurs followed by viremia and systemic dissemination as revealed by the characteristic skin rash. Most children recover uneventfully from the illness, but serious complications can occur, including pneumonia and involvement of the central nervous system (17,27,28). Despite the highly contagious nature of the disease, MV can be controlled effectively by immunization with live attenuated vaccines. The effectiveness of MV vaccines is well illustrated by the epidemiology of the disease in the United States. Prior to 1963, before use of the earliest vaccines, there were over 500,000 reported cases per year. Twenty years later, MV incidence was less than 2,000 cases per year (11,28). The availability of these effective vaccines has not eliminated the threat from MV, and measles still causes significant levels of morbidity and mortality in developing countries largely because of inadequate and unsustained vaccination efforts (17).Several effective MV vaccines were derived from a single clinical viral isolate called the Edmonston strain (28, 66). Enders et al. (20) developed the first MV vaccine by the classical approach (1) of propagating the pathogen in heterologous cells and tissues. Specifically, MV was serially propagated in semipermissive chicken embryos and chick fibroblast cells. Variations of the Enders approach have led to the development of a number of independently derived but effective Edmonstonbased vaccines (28,66).MV is a member of the genus Morbillivirus in the Paramyxoviridae family and, like other members of this family, it is an enveloped RNA virus that contains a single-strand, negativesense, nonsegmented genome (28, 47). The 16-kb MV genome encodes eight known proteins from six nonoverlapping cistrons arranged 3Ј-N-P-M-F-H-L-5Ј. The major structural polypeptide is encoded by the N (nucleocapsid) gene. The N protein is essential for packaging the genome into a ribonucleoprotein complex that serves as template for transcription, replication, and packaging into progeny virions. The P cistron specifies three polypeptides: P, C, and V. The P (phosphoprotein) polypeptide is a subunit of the viral RNA polymerase. P protein also acts as a chaperone that interacts with and regulates the cellular localization of N protein and probably assists in nucleocapsid assembly (28,33,70). The C and V polypeptides are nonstructural proteins that are translated from P mRNAs through the use of alternative reading frames; C protein is synthesized from a downstream translation start signal, whereas V protein is translated from an edited mRNA that contains an extra G residue (28,33,70). The M gene encodes the matrix protein that lines the inner surface of the viral envelope and participates in virion matur...

A panel of 23 monoclonal antibodies (MAbs) specific for the attachment (G) glycoprotein of bovine respiratory syncytial virus (BRS virus), recognizing seven antigenic areas on the G protein, was used to determine the antigenic heterogeneity among 19 BRS viruses isolated over a 20 year period from various parts of the world. The pattern of reactivity of the isolates, as determined by ELISA, identified two major subgroups of BRSV. This finding was confirmed by radioimmunoprecipitation of the G protein by the MAbs and was also demonstrated using polyclonal sera obtained from calves hyperimmunized with BRS virus strains from each subgroup. The subgroups could also be differentiated by differences in the apparent M r of the fusion (F) glycoprotein and its cleavage products. The apparent Mrs of the F o, F~ and F~ polypeptides were 73K, 46K and 17K for subgroup A strains and 77K, 46K and 23K for subgroup B strains. These studies provide evidence for two major lineages of BRS virus, similar to the situation with human RS virus.

The immunogenicity and protective efficacy of recombinant vaccinia viruses (rVV) encoding the F, G, N or M2 (22K) proteins of bovine respiratory syncytial virus (BRSV) were evaluated in calves, the natural host for BRSV. Calves were vaccinated either by scarification or intratracheally with rVV and challenged 6 to 7 weeks later with BRSV. Although replication of rVV expressing the F protein in the respiratory tract was limited after intratracheal vaccination, the levels of serum and pulmonary antibody were similar to those induced following scarification. The serum antibody response induced by the F protein was biased in favour of IgG1 antibody, whereas the G and the N proteins induced similar levels of IgG1 : IgG2, and antibody was undetectable in calves primed with the M2 protein. The F protein induced neutralizing antibodies, but

The noncoding sequence of five Edmonston vaccine viruses (AIK-C, Moraten, Rubeovax, Schwarz, and Zagreb) and those of a low-passage Edmonston wild-type (wt) measles virus have been determined and compared. Twenty-one nucleotide positions were identified at which Edmonston wt and one or more vaccine strains differed. The location of some of these nucleotide substitutions suggests that they may influence the efficiency of mRNA synthesis, processing, and translation, as well as genome replication and encapsidation. Five nucleotide substitutions were conserved in all of the vaccine strains. Two of these were in the genomic 3-terminal transcriptional control region and could affect RNA synthesis or encapsidation. Three were found within the 5-untranslated region of the F mRNA, potentially altering translation control sequences. The remaining vaccine virus base changes were found in one to four vaccine strains. Their genomic localization suggests that some may modify cis-acting regulatory domains, including the Kozak consensus element of the P and M genes, the F gene-end signal, and the F mRNA 5-untranslated sequence.