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PubMed1992

Variation in antigenicity and molecular weight of Campylobacter coli VC167 flagellin in different genetic backgrounds.

Campylobacter coli VC167 has been shown to undergo a reversible flagellar antigenic variation between antigenic type 1 (T1) and antigenic type 2 (T2). VC167 contains two flagellin genes, and the products of both genes are incorporated into a complex flagellar filament in both antigenic types. Although there are only minor amino acid changes in the flagellins expressed by T1 and T2 cells, the two antigenic types of flagellins can be distinguished by differences in apparent M(r) on sodium dodecyl sulfate-polyacrylamide gels and by immunoreactivity with T1-specific (LAH1) or T2-specific (LAH2) antiserum. The isolation of stable variants of T1 and T2 has allowed for the transfer via natural transformation of the flagellin structural genes from the T1 background into the T2 background and from the T2 background into the T1 background. In addition, the flagellin genes from VC167 T1 and T2 have been transferred into strains of Campylobacter jejuni. The results indicate that the observed antigenic variations of VC167 flagellins are dependent on the host genetic background and independent of the primary amino acid sequence. These data provide evidence that posttranslational modifications are responsible for the antigenic variation seen in VC167 flagellins.

Antigenic Variation↗
PubMed1987

Antigenic variation of caprine arthritis-encephalitis virus during persistent infection of goats.

Six caprine arthritis-encephalitis virus (CAEV)-free goats kept in strict isolation were inoculated intravenously with a cloned CAEV isolate (virus 020). At 78 weeks post-infection a virus (virus 095) isolated from one of the goats was shown to have the characteristics of CAEV, but was antigenically distinct from virus 020 and two other CAEV isolates by serum neutralization tests. Serum from the goat that had the variant virus neutralized the inoculum virus and the variant virus but serum from other inoculated goats neutralized only the inoculum virus. The variant virus and the inoculum virus were shown to co-exist in the infected goat, but the presence of the antigenic variant did not appear to be associated with an increase in severity of lesions compared with other inoculated goats.

Animals↗
PubMedDate not supplied

Genetics of antigenic variation in African trypanosomes.

The major surface antigens of Trypanosoma brucei are the VSG (variant surface glycoprotein) at the bloodstream stage, and procyclin at the procyclic stage. Variation in the VSG allows the parasite to escape the antibody response of its mammalian host. This occurs through either DNA rearrangement in the telomeric VSG gene expression site, or alternate activation, without DNA rearrangement, of different telomeric expression sites. The VSG and procyclin genes each belong to large, polycistronic transcription units. Although the promoters of these units are both active at the two main stages of the parasite life cycle, stage-specific controls operating at the level of RNA elongation and processing lead to strictly differential expression of the end products of the two units. Despite their mutually exclusive control of expression, the VSG and procyclin transcription units share common characteristics. Both contain a similar gene, and both are transcribed by the same type of RNA polymerase, unusually resistant to alpha-amanitin. Among the eight genes present in the VSG transcription unit, two may be involved in the synthesis of cyclic AMP. The function of the other genes is unknown.

Animals↗
PubMed2004

Strong positive selection and recombination drive the antigenic variation of the PilE protein of the human pathogen Neisseria meningitidis.

The PilE protein is the major component of the Neisseria meningitidis pilus, which is encoded by the pilE/pilS locus that includes an expressed gene and eight homologous silent fragments. The silent gene fragments have been shown to recombine through gene conversion with the expressed gene and thereby provide a means by which novel antigenic variants of the PilE protein can be generated. We have analyzed the evolutionary rate of the pilE gene using the nucleotide sequence of two complete pilE/pilS loci. The very high rate of evolution displayed by the PilE protein appears driven by both recombination and positive selection. Within the semivariable region of the pilE and pilS genes, recombination appears to occur within multiple small sequence blocks that lie between conserved sequence elements. Within the hypervariable region, positive selection was identified from comparison of the silent and expressed genes. The unusual gene conversion mechanism that operates at the pilE/pilS locus is a strategy employed by N. meningitidis to enhance mutation of certain regions of the PilE protein. The silent copies of the gene effectively allow "parallelized" evolution of pilE, thus enabling the encoded protein to rapidly explore a large area of sequence space in an effort to find novel antigenic variants.

Antigenic Variation↗
PubMed2001

Gene silencing and antigenic variation in malaria parasites.

Malaria remains one of the most important infectious diseases in the world today, infecting 300 to 500 million people yearly and resulting in 1 to 2 million deaths, primarily of young African children. The most severe form of this disease is caused by infection with the mosquito borne protozoan parasite Plasmodium falciparum. This parasite lives by invading and multiplying within the red blood cells of its host, causing disease through anemia resulting from red cell destruction, and also through modifications made to the surface of infected red cells. These modifications make infected cells cytoadherent or "sticky", allowing them to adhere to the walls of blood vessels, leading to obstruction of blood flow and such clinical manifestations as the often fatal syndrome of cerebral malaria. In addition, parasites are capable of undergoing antigenic variation, a process of continually changing the identity of proteins on the surface of infected cells and thus avoiding the immune response mounted by the host. This process promotes a long term, persistent infection that is difficult to clear.

Animals↗
PubMed1995

Mechanism of antigenic variation in Shigella flexneri bacilli. III. Complement sensitivity of S. flexneri 1b strains and their 3b variants selected either as Lac+ recombinants or phage F2 resistant mutants.

Several S. flexneri 1b serotype strains of clinical isolation were compared with their 3b serotype variants isolated either as Lac+ recombinants from crosses of S. flexneri x E. coli Hfr C, or F2-resistant mutants. The studied variants 3b were deprived of type I antigen but acquired type III antigen. They appeared to be less sensitive to killing action of complement present in normal bovine serum although kinetics of killing and its effectiveness differed between the strains.

Animals↗
PubMed1987

Molecular principles of antigenic variation in Neisseria gonorrhoeae.

The genome of Neisseria gonorrhoeae harbours many gene loci for the production of variant pili. Strain MS11 has two expression genes (pilE) with promoter and complete coding sequences. The remaining genes are silent (pilS) lacking the promoter and the conservative amino terminals coding sequences of pilin. The pilus genes consist of six variable minicassettes (mc's), that are flancked by strictly conserved sequences. Upon phase (P+ to P+) and antigenic (P+ to P-, or vice versa) transitions minicassettes from silent loci are transferred from silent pilus gene copies to the expression gene by gene conversion. P- variants resulting from such rearrangements still produce pilin mRNA as well as pilin, but only a few are found on the surface of those gonococci.

Antigenic Variation↗
PubMed1998

Antigenic Variation and Some Biological Properties of Wild-Type Measles Virus Strain Buk and Vaccine Strain L-16.

In some measles virus strains protein synthesis is restricted or reduced at higher temperature incubation. But in wild-type Buk strain and L-16 vaccine strain no changes in viral protein synthesis at 40 degrees C were shown. Radiolabelled Buk and L-16 proteins were precipitated with reconvalescent sera, vaccinated children's sera, subacute sclerosing panencephalitis patients' sera and rabbit antisera. There are no differences in the autoradiograms. However, antigenic variations in Buk strain proteins were discovered by using mAbs in radioimmunoprecipitation analysis. Buk strain hemagglutinin (H protein) has low binding ability in epitopes II and III in comparison with L-16 strain. Analogous changes were found in the epitope II of Buk strain phosphoprotein. Nucleocapsid, fusion and membrane proteins of the two strains have the same interactions with mAbs. In order to investigate H protein affinity with antihemagglutinins and receptors for erythrocytes a modified test for HA-inhibiting antibodies was used. But incubation time for sera and tween-ether antigens was varied from 0 min to 1.5 h. In "0 min" incubation time hemagglutinin can bind with antihemagglutinins or receptors for erythrocytes. But H protein binds more readily with antibodies. Buk strain H protein revealed antihemagglutinins in higher titers than L-16 strain antigen.

Journal Article↗
PubMed1984

Antigenic variation during infection with Neisseria gonorrhoeae: detection of antibodies to surface proteins in sera of patients with gonorrhea.

Neisseria gonorrhoeae were cultured from the urethra of male patients and from the cervix and urethra of female contacts. Isolates from a given group of individuals were of the same strain but differed considerably in terms of the molecular weight of both protein II and pili. Radioimmunoprecipitation assays showed that most patients produced serum antibodies to protein I. Antibodies to pili, when present, showed limited cross-reactivity with the different pili produced by a single strain. Antibodies to protein II were highly specific, reacting with only one of the protein II-types produced by a single strain; this observation suggested that the host immune response may be an important factor in antigenic variation. Several sera also contained antibodies to a common surface protein with a molecular weight of 43,000 that was present in all strains tested.

Antibodies, Bacterial↗
PubMed1993

Antigenic variation in gp120s from molecular clones of HIV-1 LAI.

To address the relationship between primary sequence variation in HIV-1 gp120 and its antigenic structure in a simple system, we have measured the binding of human and murine monoclonal antibodies (MAbs) to gp120 from four molecular clones of HIV-1 LAI: HxB2, HxB3, Hx10, and NL4-3. Despite the close relationship between these clones, and their relatively conserved gp120 sequences, there is considerable variation in their antigenic structure, judged by MAb reactivities to the V2, V3, and C4 domains and to discontinuous epitopes. Because of our prior studies of the determinants of MAb binding to HxB2 gp120, we can make reasonable estimates of how sequence variation among the LAI clone gp120s affects their binding of some MAbs; for other MAbs our current knowledge of gp120 structure is too limited to allow such estimates. These results indicate that small variations in primary gp120 amino acid sequence can profoundly affect recognition of this glycoprotein by all five groups of defined anti-gp120 neutralizing antibodies.

Amino Acid Sequence↗
PubMed1993

Antigenic variation of molecularly cloned SIVmac239 during persistent infection in a rhesus macaque.

Eight rhesus macaques inoculated with molecularly cloned SIVmac239 developed viremia and virus-binding antibodies, but only one (macaque 2D) developed neutralizing antibodies to the virus. Viremia persisted in macaque 2D even in the presence of neutralizing antibodies. Neutralizing antibodies in the plasma collected from macaque 2D late in infection neutralized virus isolated early in infection. In contrast, these antibodies failed to neutralize the plasma viruses isolated after the appearance of neutralizing antibodies. Only antigenic variants were isolated from blood, spleen, and lymph nodes. Viruses isolated from other macaques that did not develop neutralizing antibodies were neutralized by 2D serum and were of the parental (SIVmac239) phenotype. The variant viruses maintained their strict tropism for lymphocytes, similar to the parental virus.

Animals↗
PubMed1995

Hepatitis B surface antigen variation and protective immunity.

Hepatitis B surface antigen (HBsAg) particles consist predominantly of a glycoprotein of 226 amino acids which bears the B-cell epitopes important for the induction of protective antibody responses in humans. It has been clearly shown that the region between residues 120 and 150 of the S protein represents the a determinants common to all hepatitis B virus (HBV) isolates and is exposed on the surface of the HBV particle. Anti-a antibodies protect adults against the majority of infections irrespective of the subtype of the wild-type virus. Occasional examples of infection positive for anti-HBs antibodies have been associated with the emergence of HBV variants. In particular, asymptomatic infections have been described in vaccinated children, an observation which is associated with an amino acid change in a domain critical for anti-HBs binding. Variation in amino acid sequence is also found within the preS amino terminal extensions of the S protein, although these do not correlate with subtypic variations among the S-antigenic domains. There is no direct evidence that preS determinants per se may stimulate a protective immune response in humans, although the hepatocyte attachment domain is located in the preS1 region which is conserved between HBV isolates. The inclusion of preS specificities augments anti-HBs responses in an experimental animal; however, at the present time it is unclear as to how this may best be exploited in improving hepatitis B vaccines for human use. Variability in HBV envelope proteins has implications for the design of vaccination programmes and the diagnosis of HBV infections; however, the low frequency of HBV variants emerging in the face of increasing levels of herd immunity to hepatitis B at the present time means that the extension of immunization programmes using existing vaccines remains a priority.

Amino Acid Sequence↗
PubMed1988

Antigenic variation in Giardia lamblia.

Clones of the WB isolate of Giardia lamblia were exposed to cytotoxic mAb 6E7 which reacts with a 170-kDa surface Ag. Surviving progeny occurred at a frequency of about 1 in 1000 and were resistant to the effects of mAb 6E7. Analysis of progeny and clones of these progeny by surface radiolabeling, surface immunofluorescence, and Western blotting failed to detect the 170-kDa Ag. Loss of this Ag was associated with the appearance of a series of new surface Ag. A cytotoxic mAb (5C1) was produced to one of the newly appearing antigens (approximately equal to 64 kDa) and Giardia resistant to the cytotoxic effects of 5C1 isolated. Neither the approximately equal to 64 kDa nor the 170 kDa Ag were present and were replaced by a second series of new Ag. These studies clearly establish the loss and subsequent replacement of two antigenically distinct epitopes on Giardia derived from a single organism.

Animals↗
PubMed1988

Antigenic variation in alkaline deoxyribonuclease induced by three different strains of Epstein-Barr virus.

To determine whether biological and/or biochemical variants exist between strains of Epstein-Barr virus (EBV), we superinfected Raji cells with the nontransforming lytic strain of EBV (HR-1), and two isolates that both transform B-lymphocytes and superinfect Raji cells, B95-8, and NPC-EBV. The superinfected cells were assayed for EBV specific DNase. A new electrophoretic form of DNase was observed in cells superinfected with B95-8 EBV as compared to the enzymes induced by the HR-1 and NPC-EBV isolates. There were antigenic differences in the DNase induced by the EBV strains. Since antibody to EBV DNase is a marker for nasopharyngeal carcinoma (NPC), these data may have implications for EBV-associated disease.

Antigenic Variation↗
PubMed2003

Characterization of the vls antigenic variation loci of the Lyme disease spirochaetes Borrelia garinii Ip90 and Borrelia afzelii ACAI.

The vls locus of Borrelia burgdorferi B31 consists of 15 silent cassettes and one expression site (vlsE), and the presence of the encoding plasmid lp28-1 correlates with high infectivity. Recombination between the expression cassette and silent cassettes occurs in vivo, and this process may enable B. burgdorferi to evade the immune response. To determine the characteristics of the vls loci in other Borrelia strains, we have cloned and characterized the vls silent cassette loci of Borrelia garinii Ip90 and Borrelia afzelii ACAI, consisting of 11 vls silent cassettes and 14 vls silent cassettes respectively. The silent cassettes share 90-97% nucleotide sequence identity with one another within the Ip90 vls locus and 84-91% within the ACAI vls locus. In both organisms, the silent cassettes resemble the B31 Vls sequences in overall amino acid similarity (50-65%) and in the presence of six variable regions interspersed between six relatively invariant regions. The vlsE expression sites of these two strains have not been isolated, but transcripts of vlsE were detected by reverse transcriptase-polymerase chain reaction for both Ip90 and ACAI. In addition, the occurrence of sequence variation within the vlsE cassette region of these transcripts was verified. This study indicates that the vls loci present in B. garinii Ip90 and B. afzelii ACAI have characteristics similar to those found in B. burgdorferi B31.

Acrodermatitis↗
PubMed1998

Influence of antibodies in mother's milk on antigenic variation of Giardia lamblia in the murine mother-offspring model of infection.

In the present study, neonatal ZU.ICR mice and their mothers were infected with trophozoites of Giardia lamblia clone GS/M-83-H7 expressing the variant surface protein (VSP) H7. The infection experiments included a detailed analysis of the specificities of anti-Giardia immunoglobulin A (IgA) antibodies in mother's milk and a determination of the effects of the milk antibodies on both the growth of the parasite during in vitro cultivation and colonization of the parasite within the intestine of suckling offspring. These investigations revealed that transiently emerging milk IgA antibodies against a variant-specific 314-amino-acid N-terminal region of VSP H7 exhibit a strong parasiticidal effect on VSP H7-type trophozoites both in vitro and in vivo. These findings indicated that parasiticidal effects of local IgA antibodies against the N-terminal part of VSP H7 select for new variant types within the intestinal parasite population of suckling mice. The selective influence of such antibodies promotes in vivo antigenic variation of G. lamblia clone GS/M-83-H7 and modulates the early course of parasite infection in these animals.

Animals↗