aning of vaccine-induced immunity: is it a problem in Africa?
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Seroepidemiological evaluation of 1989-91 mass vaccination campaigns against measles, in Italy.
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In 1989-91 anti-measles vaccination campaigns were conducted in several Italian regions to vaccinate all children aged between 13 months and 10-12 years without a history of measles or measles vaccination. This study was conducted to evaluate serological status after the mass vaccination campaigns. In 1994, capillary blood samples were collected from randomly selected children, aged 2-14 years, living in 13 local health units. Antibody titres were determined by ELISA. Blood spot samples were analysed for 4114 (75.6%) of 5440 selected children. Among the 835 that reported measles before 1990, 806 (96.5%) were immune and of the 2798 vaccinated, 2665 (95.2%) were immune. The Edmoston-Zagreb (E-Z) strain vaccine was associated with a lower level of immunity than the Schwarz (SW) strain. A history of measles identified almost all immune children. Vaccination with the SW strain conferred persistent immunity (at least 5 years) in 98% of vaccinees. The strategy was able to unite natural and induced immunity. (+info)
Characterization of a new genotype of measles virus detected in China and England.
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We report the co-circulation of a new lineage of measles virus (MV) and an Edmonston-like (Ed-like) genotype of MV in China during 1995-7. Sequence analysis of 25 strains was performed on a 282 nucleotides (nt) region of the nucleoprotein (N) gene, a 450-nt region of the haemagglutinin (H) gene and a 152-nt region of the matrix (M) gene by direct sequencing of RT-PCR amplicons obtained from clinical specimens. The entire H gene was sequenced from two strains. The results showed that 24/25 Chinese strains belonged to a new genogroup and were distinct from the vaccine strains used in China and the UK, and also from MV strains previously described in Europe, Africa and the USA. The remaining strain was Ed-like. Two strains of the new genotype (IV) and one of the Ed-like genotype were also detected in the UK in 1996. (+info)
Requirements for measles virus induction of RANTES chemokine in human astrocytoma-derived U373 cells.
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Interferons and chemokines play a critical role in regulating the host response to viral infection. Measles virus, a member of the Paramyxoviridae family, induces RANTES expression by astrocytes. We have examined the mechanism of this induction in U373 cells derived from a human astrocytoma. RANTES was induced in a dose- and time-dependent manner by measles virus infection. Inhibition of receptor binding by the anti-CD46 antibody TRA-2.10 and of virus-membrane fusion by the tripeptide X-Phe-Phe-Gly reduced RANTES expression. Formalin-inactivated virus, which can bind but not fuse, and extensively UV-irradiated virus, which can bind and fuse, were both ineffective. Therefore, virus binding to the cellular receptor CD46 and subsequent membrane fusion were necessary, but not sufficient, to induce RANTES. UV irradiation of virus for less than 10 min proportionally inhibited viral transcription and RANTES expression. RANTES induction was decreased in infected cells treated with ribavirin, which inhibits measles virus transcription. However, RANTES mRNA was superinduced by measles virus in the presence of cycloheximide. These data suggest that partial transcription of the viral genome is sufficient and necessary for RANTES induction, whereas viral protein synthesis and replication are not required. This hypothesis was supported by the fact that RANTES was induced through transient expression of the measles virus nucleocapsid gene but not by measles genes encoding P or L proteins or by leader RNA in A549 cells. Thus, transcription of specific portions of measles virus RNA, such as the nucleocapsid gene, appears able to generate the specific signaling required to induce RANTES gene expression. (+info)
Structural and functional studies of the measles virus hemagglutinin: identification of a novel site required for CD46 interaction.
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The entry of measles virus (MV) into human cells is mediated by the initial attachment of the viral hemagglutinin (HA) to the complement regulatory protein CD46. Two subdomains, one each within CD46 short consensus repeats (SCRs) 1 and 2, are responsible for this interaction. However, little is known about the regions within MV HA needed for a high-affinity CD46 interaction. To better define the HA-CD46 interaction, we took three approaches: chimeric domain swapping, peptide scanning, and alanine scanning mutagenesis. Chimeras of MV HA and the closely related rinderpest virus (RPV) HA were generated and tested for cell surface expression and the ability to hemadsorb CD46+ red blood cells (RBC). Exchanges with the N terminus of RPV were tolerated as MV HA could be replaced with RPV HA up to amino-acid position 154. However, both larger swaps with RPV and a small RPV HA replacement at the C terminus aborted cell-surface expression. Peptide scanning with 51 overlapping peptides derived from three MV HA regions showed one peptide, corresponding to MV HA amino acids 468-487, blocked hemagglutination of African green monkey (AGM) RBCs and inhibited MV infection of Chinese hamster ovary cells (CHO) expressing human CD46. Alanine scanning mutants mapped sites on the MV HA that were not required for trafficking to the cell surface or function in hemagglutination as well as a novel site required for CD46 interaction, amino acids 473-477. (+info)
Events following the infections of enucleate cells with measles virus.
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The development of measles virus (Edmonston) and SSPE measles virus (Horta-Barbosa) has been examined in enucleate BSC 1 cells. New antigen synthesis in measles virus infected enucleate cells has been demonstrated by fluorescent antibody, by the formation of extensive syncytia from enucleate cells alone and by analysis of polypeptide formation by polyacrylamide gel electrophoresis. All polypeptides formed in nucleate cells were also present in enucleate cells but the amount synthesized was reduced to around 20% of that in nucleate cells. There was also a significant reduction in the amount of antigen detected by fluorescent antibody in enucleate as compared to nucleate preparations. Examination of RNA synthesis in infected enucleate cells revealed only a marginal increase in acid-insoluble material. Titration of the output of infectious virus from enucleate cells infected at both 37 and 31 degrees C indicated a consistent reduction of almost two log units compared to nucleate cells. That the enucleate cells were capable of replicating input genome at these times was demonstrated by the successful growth of respiratory syncytial virus, both at 37 and 31 degrees C. SSPE measles virus grew to higher yield in nucleate BSC 1 than measles virus but there was again a reduction of more than two log units in enucleate cells. All polypeptides synthesized in SSPE infected nucleate cells were apparent in enucleate cells. (+info)
The genome nucleotide sequence of a contemporary wild strain of measles virus and its comparison with the classical Edmonston strain genome.
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The only complete genome nucleotide sequences of measles virus (MeV) reported to date have been for the Edmonston (Ed) strain and derivatives, which were isolated decades ago, passaged extensively under laboratory conditions, and appeared to be nonpathogenic. Partial sequencing of many other strains has identified >/=15 genotypes. Most recent isolates, including those typically pathogenic, belong to genotypes distinct from the Edmonston type. Therefore, the sequence of Ed and related strains may not be representative of those of pathological measles circulating at that or any time in human populations. Taking into account these issues as well as the fact that so many studies have been based upon Ed-related strains, we have sequenced the entire genome of a recently isolated pathogenic strain, 9301B. Between this recent isolate and the classical Ed strain, there were 465 nucleotide differences (2.93%) and 114 amino acid differences (2.19%). Computation of nonsynonymous and synonymous substitutions in open reading frames as well as direct comparisons of noncoding regions of each gene and extracistronic regulatory regions clearly revealed the regions where changes have been permissible and nonpermissible. Notably, considerable nonsynonymous substitutions appeared to be permissible for the P frame to maintain a high degree of sequence conservation for the overlapping C frame. However, the cause and the effect were largely unclear for any substitution, indicating that there is a considerable gap between the two strains that cannot be filled. The sequence reported here would be useful as a reference of contemporary wild-type MeV. (+info)
Enhanced measles virus cDNA rescue and gene expression after heat shock.
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Rescue of negative-stranded RNA viruses from full-length genomic cDNA clones is an essential technology for genetic analysis of this class of viruses. Using this technology in our studies of measles virus (MV), we found that the efficiency of the measles virus rescue procedure (F. Radecke et al., EMBO J. 14:5773-5784, 1995) could be improved by modifying the procedure in two ways. First, we found that coculture of transfected 293-3-46 cells with a monolayer of Vero cells increased the number of virus-producing cultures about 20-fold. Second, we determined that heat shock treatment increased the average number of transfected cultures that produced virus another two- to threefold. In addition, heat shock increased the number of plaques produced by positive cultures. The effect of heat shock on rescue led us to test the effect on transient expression from an MV minireplicon. Heat shock increased the level of reporter gene expression when either minireplicon DNA or RNA was used regardless of whether complementation was provided by cotransfection with expression plasmids or infection with MV helper virus. In addition, we found that MV minireplicon gene expression could be stimulated by cotransfection with an Hsp72 expression plasmid, indicating that hsp72 likely plays a role in the effect of heat shock. (+info)