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PubMed1999

Antigenic variation among bovine enteric coronaviruses (BECV) and bovine respiratory coronaviruses (BRCV) detected using monoclonal antibodies.

Bovine coronavirus (BCV) causes neonatal calf diarrhea (CD) and is associated with winter dysentery (WD) in adult dairy cattle. It can also be isolated from the respiratory tracts of cattle entering feedlots. Monoclonal antibodies (MAbs) specific for the hemagglutinin esterase (HE) and spike (S) surface proteins of 2 bovine enteric coronavirus (BECV) strains and two bovine respiratory coronavirus (BRCV) strains were tested against 6 BECV strains and 6 recently isolated BRCV strains, in order to characterize the antigenicity of BCV strains with varied tissue tropisms. All MAbs had high immunofluorescence (IF) titers against BECV and BRCV strains, indicative of conserved cross-reactive epitopes. In hemagglutination inhibition (HI) tests, the S-MAbs were more broadly reactive than HE-MAbs. The BRCV and CD MAbs were more broadly reactive in HI than the WD MAbs. The HA activity of the Mebus vaccine CD strain was not inhibited by any of the MAbs tested. The HI activity of BRCV strain R6 was unique among the 6 BRCV isolates. In virus neutralization assays, MAbs to the BRCV strain R4 neutralized all 6 BECV strains tested. Antigenic variation exists among both BECV and BRCV strains, but it cannot be attributed soley to the clinical origin of the strain.

Animals↗
PubMed1995

The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes.

The human malaria parasite Plasmodium falciparum evades host immunity by varying the antigenic and adhesive character of infected erythrocytes. We describe a large and extremely diverse family of P. falciparum genes (var) that encode 200-350 kDa proteins having the expected properties of antigenically variant adhesion molecules. Predicted amino acid sequences of var genes show a variable extracellular segment with domains having receptor-binding features, a transmembrane sequence, and a terminal segment that is a probable submembrane anchor. There are 50-150 var genes on multiple parasite chromosomes, and some are in clustered arrangements. var probes detect two classes of transcripts in steady-state RNA: 7-9 kb var transcripts, and an unusual family of 1.8-2.4 kb transcripts that may be involved in expression or rearrangements of var genes.

Amino Acid Sequence↗
PubMed1983

DNA rearrangements and antigenic variation in Trypanosoma equiperdum: expression-independent DNA rearrangements in the basic copy of a variant surface glycoprotein gene.

Antigenic variation in Trypanosoma equiperdum is associated with the sequential expression of variant surface glycoprotein (VSG) genes in a process which involves gene duplication and transposition events. In this paper we present evidence that the genomic environment of the VSG-1 basic copy gene, the template for duplicated, expression-linked VSG-1 genes, differs in every trypanosome clone examined. This variation is thus independent of the expression of the VSG-1 gene, and it also appears to be restricted to the 3' genomic environment. It is also demonstrated that the DNA located 3' to the VSG-1 basic copy gene is moderately sensitive to digestion when the nuclei of either expressor or non-expressor trypanosomes are treated with DNase I.

Animals↗
PubMed1990

Antigenic variations in bovine viral diarrhea viruses detected by monoclonal antibodies.

Five murine monoclonal antibodies (MAbs) against the NADL strain of bovine viral diarrhea (BVD) virus were developed, identified, and characterized. Four of the MAbs were directed against a 53-kilodalton (kDa) viral protein, and one was specific to a 47-kDa polypeptide. Competitive radioimmunoassay showed that two MAbs were specific to related epitopes of the 53-kDa protein, and the other three MAbs were each specific to a different epitope. The MAbs were used to study heterogeneity among BVD virus strains. Various degrees of reactivity of cytopathic and noncytopathic virus isolates were detected by virus neutralization and immunofluorescence assays. The virus isolates were divided into six groups based on the neutralization test. The results indicated that the 53-kDa glycoprotein of BVD virus is the major protein involved in virus neutralization and that only a few epitopes of the protein contribute to the neutralization. None of the MAbs neutralized all the BVD virus isolates tested in this study, suggesting antigenic variations among BVD virus isolates.

Animals↗
PubMed1985

Antigenic variation of indigenous streptococci.

Isolates of Group D streptococci indigenous to the murine oral cavity were studied to detect the occurrence of antigenic variation. Group D streptococci cultured from molar homogenates of Balb/c mice were randomly selected for study on the basis of distinctive colony morphology. Isolates obtained over a 12-week period were biotyped using the API 20S system, and subjected to Lancefield extraction and rocket immunoelectrophoresis for serotyping. All isolates were compared with an arbitrarily selected standard test strain (W1S-1) isolated the first week of the first experimental series. Four biotypes were encountered during the first week of two experimental series. Two very unusual biotypes detected during the first experimental series persisted throughout that series, as did two more common biotypes throughout the second experimental series. Anti-W1S-1 serum produced three precipitin bands (antigens O, D, and K) against W1S-1 Lancefield extract and against the respective biotypes detected during the first week of the two series. Of the three antigens detected, only the group antigen (D) did not vary during either experimental series. Antigenic variants lacking the O or K antigen and bearing these distinctive phenotypes were repeatedly isolated in subsequent weeks. Ultimately, 16% of 190 strains isolated during the first series and 26% of 167 strains isolated during the second series proved to be antigenic variants of the predominant biotypes detected in both series.

Animals↗
PubMed2007

A sirtuin in the African trypanosome is involved in both DNA repair and telomeric gene silencing but is not required for antigenic variation.

Silent information regulator 2 (Sir2)-related proteins or sirtuins function as NAD(+)-dependent deacetylases or ADP ribosylases that target a range of substrates, thereby influencing chromatin structure and a diverse range of other biological functions. Genes encoding three Sir2-related proteins (SIR2rp1-3) have been identified in the parasitic trypanosomatids, early branching protozoa with no previously reported transcriptional silencing machinery. Here we show that, in the mammalian-infective bloodstream-stage of the African trypanosome, Trypanosoma brucei, SIR2rp1 localizes to the nucleus while SIR2rp2 and SIR2rp3 are both mitochondrial proteins. The nuclear protein, SIR2rp1, controls DNA repair and repression of RNA polymerase I-mediated expression immediately adjacent to telomeres. Antigenic variation, however, which involves the silencing and Pol I-mediated transcriptional switching of subtelomeric variant surface glycoprotein genes, continues to operate independent of SIR2rp1.

Amino Acid Sequence↗
PubMed1980

Virulence-related physiological changes and antigenic variation in populations of Streptococcus mutans colonizing gnotobiotic rats.

The purpose of this study was to determine if populations of Streptococcus mutans which were undergoing antigenic variation while colonizing gnotobiotic rats concomitantly became altered in physiological characteristics which affected their virulence. S. mutans strain JBP (serotype c), which was freshly isolated from a carious lesion in a 6-year old child, was used to inoculate gnotobiotic rats; uninfected animals served as controls. Substrains were isolated from animals 1, 2, 3, 4, and 12 weeks after infection; samples of pilocarpine-stimulated saliva were also obtained from representative animals for antibody analyses. Isolates derived from stock cultures of strain JBP proved to be homogeneous with respect to all of the physiological characteristics monitored. However, substrains isolated from the animals within 4 weeks after infection were altered with respect to their ability to agglutinate in the presence of sucrose, their ability to form adherent growth in sucrose broth, and the terminal pH attained in glucose broth. Some isolates obtained 12 weeks after infection no longer synthesized detectable levels of c antigen or intracellular glycogen, and they formed atypical smooth colonies on mitis salivarius agar. With an enzyme-linked immunosorbent assay, low levels of immunoglobulin A (IgA) antibodies reactive with whole JBP cells were detected in saliva samples of uninfected control animals at each sampling period; these evidently were induced to antigens contained in the diet of the animals. Significantly higher levels of IgA antibodies were present in saliva samples from animals infected with strain JBP for 3 weeks or longer. Thus, the emergence of antigenic and physiological variants of S. mutans in the animals was paralleled by increased levels of salivary IgA antibodies. The reactivity of salivary IgG with JBP cells was low, and it fluctuated in both groups of animals. No antibodies of the IgM class were detected. When tested in gnotobiotic rats, several variants, including strains which no longer formed typical rough colonies or adherent growth in sucrose broth, proved much less virulent than parental strain JBP in inducing carious lesions. Prior oral immunization, which resulted in higher levels of salivary and serum IgA antibodies reactive with strain JBP, was found to accelerate the emergence of smooth-colony variants in the animals; it was also associated with decreased streptococcal population levels on the teeth and in feces of the rats. It is suggested that part of the mechanism by which artificial immunization leads to a reduction in dental caries development in experimental animals is due to the earlier selection of less virulent streptococcal populations.

Animals↗
PubMed1990

Demonstration of antigenic variation among isolates of human cytomegalovirus using monoclonal antibodies and indirect ELISA.

An indirect ELISA was developed for the detection of antigenic differences between isolates of human cytomegalovirus (HCMV) using a monoclonal antibody to an early (67 kDa) antigen. Antibody binding curves were analyzed using a microcomputer program (LISACRV) based on a nonlinear logistical model. The derivation of values for the average intrinsic association constant for seven isolates of HCMV and the prototype AD169 strain revealed significant differences between them. Because of the importance of HCMV as a pathogen, especially in immunosuppressed and AIDS patients, further investigation of the biological significance of differences between isolates of HCMV is clearly warranted.

Antibodies, Monoclonal↗
PubMed2000

Antigenic variation among foot-and-mouth disease virus type A field isolates of 1997-1999 from Iran.

The sequences of the antigenically relevant capsid proteins VP1-3 of 10 isolates obtained during an epizootic of serotype A foot-and-mouth disease virus in Iran, and collected within two and a half years, were found to be highly similar. However, each isolate differed by at least one amino acid from all others. This prompted us to analyze the immunological reactivity of the isolates. To this end, monoclonal antibodies (mAbs) against one isolate were generated and characterized with regard to neutralizing activity and reactivity with trypsinized virus. These mAbs as well as others raised against A22 virus were used for antigen profiling. This distinguished four antigenic conditions among the isolates and 16 reactivities among the mAbs. These findings, together with the observed sequence differences indicated the location of several epitopes. Many mAbs recognized the minor antigenic sites on VP2 and 3 and some the major site, the GH-loop of VP1. One epitope was composed of residues of the capsid proteins VP1 and 2.

Amino Acid Sequence↗
PubMed1986

Antigenic variation between human respiratory syncytial virus isolates.

Three hybridoma antibodies, prepared against the RSN-2 strain of human respiratory syncytial (RS) virus, have been used to identify antigenic variation between 41 isolates of RS virus collected from widely separated geographical regions over a period of 29 years. One antibody was directed against an antigenic site on the virus fusion protein, VP70. This site was shared by 21 virus isolates tested and its recognition by the antibody was sensitive to the presence of 2-mercaptoethanol. The remaining two antibodies used react against the virus phosphoprotein, VPP32. Two independent sites were recognized on VPP32 by these antibodies. One antibody reacted with all of the virus isolates screened while the second reacted with only 21 out of the 41 virus isolates. On the basis of the variable epitope, two antigenic types of human RS virus were identified. The distribution of each antigenic group among 28 RS virus isolates from the Grampian Region, north-east Scotland, collected between 1982 and 1984 was determined. The reactivity of these antibodies was examined using immunofluorescence staining and by immunoblotting; the latter technique also revealed that the electrophoretic mobility of VPP32 varied in parallel with the variable antigenic site.

Animals↗
PubMed1983

Antigenic variation during cellular aging in Paramecium tetraurelia.

Clones of Paramecium tetraurelia undergoing cellular aging were exposed to two antisera, anti-32 and anti-25, raised against surface antigen isolated from cells grown at 32 degrees C or 25 degrees C. When young clones were exposed to the two antisera about 50% were immobilized by anti-32 while others were not immobilized by either antisera. These clones were grouped as group A or B depending upon their sensitivity or nonsensitivity to the two antisera. Young cells of group A were immobilized by anti-32 and during aging these cells either maintained the same antigenic type or transformed to another. Young group B clones were not immobilized by either antisera but gradually became sensitive to anti-32. Some clones from both groups showed sensitivity to both antisera. The possible mechanism of antigenic variation during fission age is discussed.

Animals↗
PubMed2001

Antigenic variation among isolates of infectious salmon anaemia virus correlates with genetic variation of the viral haemagglutinin gene.

Infectious salmon anaemia virus (ISAV), an orthomyxovirus-like virus, is an important fish pathogen in marine aquaculture. Virus neutralization of 24 ISAV isolates in the TO cell line using rabbit antisera to the whole virus and comparative sequence analysis of their haemagglutinin (HA) genes have allowed elaboration on the variation of ISAV isolates. The 24 viruses were neutralized to varying degrees, revealing two major antigenic groups, one American and one European. Sequence analysis of the HA gene also revealed two groups of viruses (genotypes) that correlated with the antigenic groupings. The two HA subtypes had nucleotide sequence identity of only < or =79.4% and amino acid sequence identity of < or =84.5% whereas, within each subtype, the sequence identities were 90.7% or higher. This grouping was also evident upon phylogenetic analysis, which revealed two distinct phylogenetic families. Between the two groups, the amino acid sequence was most variable in the C-terminal region and included deletions of 4-16 amino acids in all isolates relative to ISAV isolate RPC/NB-980 280-2. In order to view the relationships among these sequences and the HA sequences of the established orthomyxoviruses, a second phylogenetic tree was constructed which showed the ISAV sequences to be more closely related to sequences from Influenzavirus A and Influenzavirus B than to sequences from Influenzavirus C and Thogotovirus. The extensive deletions in the gene of European ISAV isolates lead us to speculate that the archetypal ISAV was probably of Canadian origin.

Amino Acid Sequence↗