Molecular genetics of antigenic variation in trypanosomes.
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Animals↗
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Results for “Antigenic Variation”
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Chemical basis of antigenic variation in foot-and-mouth disease virus.
One of the difficulties in controlling foot and mouth disease by vaccination is the occurrence of the virus as seven distinct serotypes because immunity conferred by vaccination against one serotype leaves the animals susceptible to infection by the other six. Moreover, the antigenic variation, even within a serotype, can be so great that immunity against the homologous strain of virus need not necessarily ensure protection against infection by other viruses within that serotype. Here we report the separation of three natural antigenic variants, distinguishable in cross-neutralization tests from an isolate of foot-and-mouth disease virus (FMDV). The serological differences could also be demonstrated by antisera elicited by synthetic peptides corresponding to residues 141-160 of the capsid polypeptide VP1, showing that this region contains a major immunogenic site of the virus. The results have practical implications for the choice of viruses for vaccine production.
Amino Acid Sequence↗
Role of O-antigen variation in the immune response.
The O antigen is an extremely variable surface polysaccharide of Gram-negative bacteria. This variation is thought to allow the various clones of a species each to present a surface that offers a selective advantage in the niche occupied by that clone. The interactions between O antigen and the immune system are central to determining the selective advantage of each clone.
Animals↗
Surface proteins of pathogenic "Neisseria": antigenic variation and conserved epitopes.
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Antigenic Variation↗
Antigenic variation between three strains of rinderpest virus detected by kinetic neutralisation and competition ELISA using early rabbit antisera.
Strains of rinderpest virus (RV) with high and low virulence were compared with cell culture-attenuated RV for antigenic differences. Sera collected from rabbits 1 week after inoculation with live virus distinguished between homologous and heterologous strains by kinetic neutralisation and competition ELISA.
Animals↗
Morphological and antigenic variations of human T cell leukemia virus type I particles in human lymphocytes.
HTLV-I particles grown in 4 human lymphocyte cultures were observed by electron microscopy. Particles in all cell lines showed marked size and structural variations that were characteristic of each cell line. Profiles of size-distributions were found to be similar among virus particles of the same origin in different cell lines. Immunogold electron microscopy using monoclonal antibody to HTLV-I-p15, -p19, or -p24 revealed varying reactivities of individual particles. By double-labeling technique using antibody to HTLV-I-p19 or -p24, particles were found to be classifiable into 4 groups: p19+p24+, p19+p24-, p19-p24%, and p19-p24-. Each cell line showed the characteristic profile of distributions of virus particles of each group as observed at different in vitro passage levels. These antibodies reacted with certain structures in the extracellular space and in the cytoplasm. Results of this study demonstrate variations in morphology and antigenicity, as well as the morphogenesis of HTLV-I particles in different host cells.
Cell Line↗
NATURAL GENOMIC AND ANTIGENIC VARIATION IN WHITEFLY-TRANSMITTED GEMINIVIRUSES (BEGOMOVIRUSES).
Begomoviruses have circular single-stranded DNA genomes, cause many diseases of dicotyledons in areas with warm climates and are transmitted by whiteflies of the Bemisia tabaci complex. Their genomic and antigenic variation represents geography-related lineages that have little relation to host range. Genomic variation resulting from mutation is amplified by acquisition of extra DNA components, pseudo-recombination and recombination, both intraspecific and interspecific. Recombination, especially interspecific recombination, seems the key mechanism for generating novel virus forms, for enhancing biological fitness of pseudo-recombinants derived from closely related species and for maintaining the flow of genetic material among different geminiviruses occurring in the same geographical region. Recent begomovirus epidemics reflect favorable conjunctions of plant, vector, and viral (e.g. emergence of a novel recombinant virus) factors. Such epidemics typically result in co-infection of plants with different begomoviruses, leading to the appearance of further variants, especially recombinants. In their patterns of variation and evolution, begomoviruses differ greatly from plant viruses with RNA genomes.
Journal Article↗
Antigenic variation in amnion cells after growth in tissue culture in relation to the inhibition of enteroviruses by anticellular serum.
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Amnion↗
Detection of antigenic variation in influenza virus neuraminidase by the ESSEN-NIT and the WHO standard procedure.
A new rapid modified micro-neuraminidase-inhibition test (ESSEN-NIT) has recently been described. This test was originally devised to facilitate large-scale screening for serum antibodies to influenza virus neuraminidase. It was shown that this test yielded results comparable to those obtained with the WHO standard procedure. Our report presents data on the comparison between the WHO method and the ESSEN-NIT with respect to their capability in detecting antigenic differences in neuraminidase of various strains of influenza A viruses belonging to the H3N2 subtype family. Two antiserums against the N2 antigens of the A/Hongkong/1/68 (X15HK) and of the A/Port Chalmers/1/73 (X42) recombinant strains were used in characterization experiments. The results obtained indicate that the ESSEN-NIT is at least as sensitive in detecting antigenic variations of neuraminidase as the WHO standard procedure. The drift of the N2 enzyme which occurred as early as 1969 and is known to continue to date, could be clearly demonstrated. Major and minor antigenic changes of neuraminidase in representative influenza isolates were equally well detected by both assays. The ESSEN-NIT offers the advantage of speed, economy, and computerized evaluation of data.
Antigens, Viral↗
Genomic and antigenic variation among rotavirus strains circulating in a large city of Argentina.
Knowledge of the antigenic diversity of rotaviruses circulating in a region should be acquired before introducing a rotavirus vaccine. In a collection of 151 rotavirus-positive samples from Mendoza, Argentina, strain diversity was evaluated utilizing G-typing monoclonal antibodies (MAbs), reverse-transcriptase-polymerase chain reaction (RT-PCR) G and P typing, and electropherotyping (PAGE). The G type of 137 (91%) specimens was determined. Typing MAb reactivity with the homologous type ranged from 25-94%. For the seven G1 MAbs utilized, 28 patterns of reactivity among 68 G1 strains occurred. For the 48 G2 strains, six patterns of reactivity occurred utilizing three G2-specific MAbs. Of the 92 samples G- and P-typed by reverse-transcriptase-polymerase chain reaction, 89% had single G/P combinations: eight G1[P4], one G1[P6], twelve G1[P8], 58 G2 [P4], and two G2 [P6]. Nine samples had more than one G type with a single P type, one sample had two P types associated with one G type, and one sample contained multiple G and P types. Twenty-nine PAGE patterns occurred for all G types, but differences of antigenic reaction did not predict differences in migration of gene segments 7, 8, and 9. For three specimens showing discordant results between G type by enzyme-linked immunosorbent assay (EIA) and RT-PCR, we observed unexpected electropherotypes. Complementary evaluation by RT-PCR and MAb-based EIA with multiple typing MAbs revealed genetic and antigenic diversity of circulating rotaviruses, including extensive intratypic variation of the G1 and G2 neutralization antigens, in Mendoza during a single season of rotavirus activity.
Antibodies, Monoclonal↗
Antigenic variation of core, NS3, and NS5 proteins among genotypes of hepatitis C virus.
Assays that detect antibody to hepatitis C virus (HCV) are used to screen blood donors and patients with hepatitis. Current enzyme-linked immunosorbent assay (ELISA)-based methods are invariably based upon antigens from expressed recombinant proteins or oligopeptides from HCV type 1. Some HCV antigens used in screening assays are coded by regions of the HCV genome that show extensive variability; therefore, HCV type 1-based assays may be less effective for the detection of antibody elicited by infection with other genotypes. In this study, we have measured antibody reactivity of sera from 110 hepatitis C patients infected with type 1b, 3a, or 4a to genotype-specific and cross-reactive epitopes present in recombinant proteins from HCV genotypes 1b (core, NS3, and NS5), 3a (NS3, NS5), and 4a (core, NS3), corresponding to those used in current third-generation screening ELISAs. By comparing the serological reactivities of sera to type-homologous and type-heterologous antigens, we detected a significant type-specific component to the reactivity to NS3 (61 to 77% of the total reactivity) and NS5 (60% of the total reactivity). Furthermore, despite the similarities in the amino acid sequences of the core antigens of type 1b and type 4a, we also found significantly greater reactivity to type-homologous antigens, with approximately 25% of reactivity being type specific. These findings are consistent with previous findings of fivefold weaker reactivity of sera from HCV type 2- and HCV type 3-infected blood donors in the currently used third-generation ELISAs and suggest that these assays are suboptimal for screening populations in which the predominant genotype is not type 1.
Amino Acid Sequence↗
Changes in telomere length associated with antigenic variation in Trypanosoma brucei.
In the IsTaR 1 serodeme, we have identified variant surface glycoprotein (VSG) genes in nine different telomeric sites. We have measured the distance from the 3' end of these VSG genes to the end of the chromosome (the 'telomere length') in 20 variant antigen types (VATs) of the serodeme. Analyses of the changes in telomere length during 19 antigenic switches involving eight telomeric sites indicate a median increase in telomere length of 0.6 kilobase pairs during each switch. This may be accounted for by the 6-10 bp increase in telomere length per generation associated with DNA replication described by others. The changes in telomere lengths do not form a normal distribution since a substantial fraction show unusually large increases in telomere length or decreases in telomere length during an antigenic switch. These changes are probably caused by recombinations 3' to the VSG gene. No significant differences were detected in the behavior of telomeres at each of the eight different telomeric sites, nor were changes in telomere lengths significantly different between different antigenic switches. However, it was found that those telomeres where transcription was activated during the antigenic switch showed a significantly greater increase in telomere length than those telomeres not involved in regulation of VSG gene expression. Conversely, there was a strong correlation between transcriptional inactivation of a telomeric expression site and a decrease in telomere length. These findings suggest that processes (possibly genomic recombinations) 3' to the VSG gene coding region may be associated with a change in the transcriptional status of the VSG gene.
Animals↗
Detection of antigenic variation among strains of Mycoplasma gallisepticum by enzyme-linked immunosorbent inhibition assay (ELISIA) and Western blot analysis.
Polyclonal antisera (PCA) to three Mycoplasma gallisepticum (MG) strains (F, S6, and A5969) produced in rabbits were used in enzyme-linked immunosorbent inhibition assay (ELISIA) and Western blot analysis to examine antigenic variability among these strains of MG. In ELISIA, inhibiting antigen of the same strain used for immunization always led to the greatest percentage inhibition of PCA reactivity. Western blot analysis of antigens of four MG strains demonstrated both common and restricted patterns of immune recognition among the three PCAs.
Animals↗
[Sequence analysis of the HA1 regions of hemagglutinin gene from influenza viruses (H3N2) isolated from children in Beijing in 2004 indicated antigenic variation].
OBJECTIVE: To identify variations in hemagglutinin genes from influenza viruses (H3N2) isolated from infants and young children with acute respiratory infection (ARI) between March, 2004 and April 2005. METHODS: RNAs from influenza A virus strains (subtype H3) isolated from specimens collected from ARI children were extracted followed by amplification for HA1 fragments from hemagglutinin (HA) genes by RT-PCR. The sequences of the fragments were defined by direct sequencing for the PCR products or the target inserts after the PCR fragments were cloned into the TA-cloning vector pBS-T and analyzed by bioinformatic software. RESULTS: Fragments of 987 bps of HA1 (encoding 329 amino acids) from a total of 32 strains of influenza A virus (subtype H3) isolated from the 2004 season and 1 from the 2003 season were amplified and the sequences were compared with vaccine reference strains recommended by WHO which were used in recent years. There were several consistent amino acid variations which involved in both antigenic epitopes A and B and receptor binding site (RBS) for isolated strains in the 2004 influenza season compared with the vaccine strains used during the recent years and the virus strains isolated in March 2004, indicated the antigenic drift of the viruses isolated in 2004 influenza season may lead to variant viruses. CONCLUSION: The variations of the HA genes from influenza virus (subtype H3) strains in the 2004-2005 influenza season were confirmed by sequence analysis for the HA1 regions of the hemagglutinin genes, which indicate that the antigenic drift would have been caused by the diversification of the genes and the efficacy of the recently used vaccines should be kept under close watch.
Antigenic Variation↗
Mechanism of antigenic variation in Mycoplasma pulmonis: interwoven, site-specific DNA inversions.
The chromosome of the murine pathogen Mycoplasma pulmonis undergoes rearrangements at a high frequency. We show that some of these rearrangements regulate the phase-variable expression of a cluster of genes (the vsa locus) that encode the variable V-1 surface antigens. Only one vsa gene is associated with an expression site; the other vsa genes are transcriptionally silent. The silent genes lack the 5' end region (promoter and ribosome-binding site) that is present in the expressed gene, and DNA rearrangements regulate gene expression by reassorting the 5' end region from an expressed gene with the 3' end region from a previously silent gene. All vsa rearrangements identified so far are site-specific DNA inversions that occur between copies of a specific 34 bp sequence that is conserved in each vsa gene. Interestingly, DNA inversions within the vsa locus apparently occur in concert with inversion of the hsd1 element, which regulates restriction and modification activity in M. pulmonis.
Amino Acid Sequence↗
Exploration of antigenic variation in gp120 from clades A through F of human immunodeficiency virus type 1 by using monoclonal antibodies.
The reactivities of a panel of 14 monoclonal antibodies (MAbs) with monomeric gp120 derived from 67 isolates of human immunodeficiency virus type 1 of clades A through F were assessed by using an antigen-capture enzyme-linked immunosorbent assay. The MAbs used were all raised against gp120 or gp120 peptides from clade B viruses and were directed at a range of epitopes relevant to human immunodeficiency virus type 1 neutralization: the V2 and V3 loops, discontinuous epitopes overlapping the CD4-binding site, and two other discontinuous epitopes. Four of the five V3 MAbs showed modest cross-reactivity within clade B but very limited reactivity with gp120s from other clades. These reactivity patterns are consistent with the known primary sequence requirements for the binding of these MAbs. One V3 human MAb (19b), however, was much more broadly reactive than the others, binding to 19 of 29 clade B and 10 of 12 clade E gp120s. The 19b epitope is confined to the flanks of the V3 loop, and these sequences are relatively conserved in clade B and E viruses. In contrast to the limited reactivity of V3 MAbs, CD4-binding site MAbs were much more broadly reactive across clades, two of these MAbs (205-46-9 and 21h) being virtually pan-reactive across clades A through F. Another human MAb (A-32) to a discontinuous epitope was also pan-reactive. The CD4-binding site is strongly conserved between clades; but when considering the epitopes near the CD4-binding site, clade D gp120 appears to be the most closely related to clade B and clade E appears to be the least related. A tentative rank order for these epitopes is B/D-A/C-E/F. V2 MAbs reacted sporadically within and between clades, and no clear pattern was observable. While results from binding assays do not predict neutralization serotypes, they suggest that there may be antigenic subtypes related, but not identical, to the genetic subtypes.
Amino Acid Sequence↗
Control of antigenic variation in African trypanosomes.
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Amino Acid Sequence↗
Antigenic variation of Campylobacter flagella.
Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of flagella dissociated from strains of Campylobacter coli and Campylobacter jejuni belonging to the heat-labile serogroup LIO 8 showed that some strains were capable of producing flagellin subunits of two different molecular weights (MrS), 59,500 and 61,500. Immunoelectron microscopy of cultures of the type strain of this serogroup, C. coli VC167, showed the presence of two flagellum filaments of different antigenic specificity. Epitopes on the surface of one of these flagella bound antibodies in LIO 8 typing antiserum, and Western blotting (immunoblotting) and immunoprecipitation showed that the flagellum was composed of flagellin of Mr 61,500. The other flagellum antigenic type did not bind LIO 8 antibodies but did possess serospecific epitopes which bound a second polyclonal antiserum, LAH2. This second antigenic flagellum type was composed of the Mr 59,500 flagellin. Cells producing either of the flagellum antigenic types serotyped as LIO 8, indicating that flagella composed of the Mr 61,500 flagellin do not carry the serological determinants for this serogroup. The ability of C. coli VC167 to produce these flagella of different subunit MrS was shown to represent a bidirectional antigenic variation. When measured in culture medium, the phase 1-to-phase 2 transition occurred at a rate of approximately 2.0 x 10(-5) per cell per generation, and the phase 2-to-phase 1 transition occurred at a rate of 1.2 x 10(-6) per cell per generation.
Antibodies↗