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PubMed1995

Characterization of repetitive DNA in the Mycoplasma genitalium genome: possible role in the generation of antigenic variation.

We have characterized a family of repetitive DNA elements with homology to the MgPa cellular adhesion operon of Mycoplasma genitalium, a bacterium that has the smallest known genome of any free-living organism. One element, 2272 bp in length and flanked by DNA with no homology to MgPa, was completely sequenced. At least four others were partially sequenced. The complete element is a composite of six regions. Five of these regions show sequence similarity with nonadjacent segments of genes of the MgPa operon. The sixth region, located near the center of the element, is an A+T-rich sequence that has only been found in this repeat family. Open reading frames are present within the five individual regions showing sequence homology to MgPa and the adjacent open reading frame 3 (ORF3) gene. However, termination codons are found between adjacent regions of homology to the MgPa operon and in the A+T-rich sequence. Thus, these repetitive elements do not appear to be directly expressible protein coding sequences. The sequence of one region from five different repetitive elements was compared with the homologous region of the MgPa gene from the type strain G37 and four newly isolated M. genitalium strains. Recombination between repetitive elements of strain G37 and the MgPa operon can explain the majority of polymorphisms within our partial sequences of the MgPa genes of the new isolates. Therefore, we propose that the repetitive elements of M. genitalium provide a reservoir of sequence that contributes to antigenic variation in proteins of the MgPa cellular adhesion operon.

Adhesins, Bacterial↗
PubMed1983

Analysis of antigenic variation in equine 2 influenza A viruses.

Influenza outbreaks involving viruses of the H3N8 subtype (equine 2) often occur in vaccinated horses. For this reason, a series of influenza viruses of the H3N8 subtype were examined to determine if antigenic variation could be detected in isolates during the period 1963-81. Antigenic analyses with post-infection ferret sera and monoclonal antibodies showed that the haemagglutinins of recent isolates were antigenically distinguishable from the prototype A/eq/Miami/1/63 and that antigenically distinguishable groups of equine 2 viruses co-circulate in the horse population. Based on these studies, it is recommended that a recent equine strain, A/equine/Fontainebleu/1/79 or A/equine/Kentucky/1/81, serve as an additional prototype strain for this subtype.Antigenic variation in equine 2 viruses may be of epidemiological significance, yet the overall conservation of these strains makes it unlikely that vaccine failures can be attributed solely to antigenic changes in these viruses. A sufficiently potent vaccine, containing a current representative of the most prevalent equine 2 strain, may improve the protection afforded by equine vaccines.

Animals↗
PubMed1992

Evolution of the capsid protein genes of foot-and-mouth disease virus: antigenic variation without accumulation of amino acid substitutions over six decades.

The genetic diversification of foot-and-mouth disease virus (FMDV) of serotype C over a 6-decade period was studied by comparing nucleotide sequences of the capsid protein-coding regions of viruses isolated in Europe, South America, and The Philippines. Phylogenetic trees were derived for VP1 and P1 (VP1, VP2, VP3, and VP4) RNAs by using the least-squares method. Confidence intervals of the derived phylogeny (significance levels of nodes and standard deviations of branch lengths) were placed by application of the bootstrap resampling method. These procedures defined six highly significant major evolutionary lineages and a complex network of sublines for the isolates from South America. In contrast, European isolates are considerably more homogeneous, probably because of the vaccine origin of several of them. The phylogenetic analysis suggests that FMDV CGC Ger/26 (one of the earliest FMDV isolates available) belonged to an evolutionary line which is now apparently extinct. Attempts to date the origin (ancestor) of the FMDVs analyzed met with considerable uncertainty, mainly owing to the stasis noted in European viruses. Remarkably, the evolution of the capsid genes of FMDV was essentially associated with linear accumulation of silent mutations but continuous accumulation of amino acid substitutions was not observed. Thus, the antigenic variation attained by FMDV type C over 6 decades was due to fluctuations among limited combinations of amino acid residues without net accumulation of amino acid replacements over time.

Amino Acid Sequence↗
PubMed1991

Naturally occurring mutations within HIV-1 V3 genomic RNA lead to antigenic variation dependent on a single amino acid substitution.

In a study on the evolution of genomic diversity of HIV-1, genomic RNA was isolated from serum of two individuals. Starting at the time of primary infection we collected six samples of serum from each patient over a period of 5 years. Ninety-four cDNA clones (50 of patient 1 and 44 of patient 495) of part of the envelope coding region including the principal neutralization domain (PND) were sequenced. Around the time of antibody seroconversion, genomic RNA levels reached a peak and the population of sequences was highly homogeneous. In the course of the infection, the number of amino acid substitutions accumulated, which led to a higher genomic diversity within successive samples and a drift in the consensus sequence, progressively differing from the first found consensus sequence. Fixation of a substitution at glycoprotein 120 amino acid 308 was observed in both patients between two time points (patient 1, H----P; patient 495, P----H). With the use of 16-meric synthetic peptides, differing only at the 308 position (H308 versus P308), antibody binding specificity was found to be dependent on this difference. In patient 495, the nonconservative (P308----H) substitution reduced the binding affinity with the patient's antibodies. Furthermore, antibody competition assays showed that the observed substitution at position 308 elicited a new antibody population, indicating antigenic variation. After the decline of V3-specific antibodies, the simultaneous increase in genomic RNA levels and progression to AIDS in patient 495, a new variant with major changes in the PND emerged, again forming a homogeneous population of sequences.

Acquired Immunodeficiency Syndrome↗
PubMed1973

Antigenic variation in current human type A influenza viruses: antigenic characteristics of the variants and their geographic distribution.

Outbreaks of influenza due to the virus A/Hong Kong/1/68 (H3N2) began in 1968 and are still occurring. The haemagglutinin of this virus is different from that of the A/Singapore/1/57 virus (the "Asian" strain) but the neuraminidase antigens are the same. Between 1968 and 1971 only minor antigenic "drift" in the haemagglutinin was noted, but in recent months 2 isolates have been identified in which considerable "drift" has occurred in the haemagglutinin and in the neuraminidase antigens. One, A/Hong Kong/5/72 (H3N2), was first detected in outbreaks in Hong Kong between November 1971 and January 1972 and was predominant there and in Korea but did not become widely disseminated. The second strain, A/England/42/72 (H3N2), has been isolated in winter outbreaks in the southern hemisphere and now appears to be the predominant strain in the northern hemisphere. The characteristics of the strains are described.

Africa↗
PubMed1996

A newly identified immunodominant membrane protein (pMB67) involved in Mycoplasma bovis surface antigenic variation.

Mycoplasma bovis is a bovine pathogen able to cause systemic disease. It possesses a series of prominent, structurally related yet clearly distinguishable membrane lipoproteins on the cell surface. These variable surface proteins (Vsps) undergo highly dynamic and spontaneous changes in size and expression and are key immunogenic components. They may play a critical role as mediators of adherence to host cells and in escaping immune destruction. In this report, we define a novel, Vsp-unrelated membrane protein also associated with M. bovis surface antigenic variation. This protein has an apparent molecular mass of 67,000 Da in the type strain PG45 and was designated pMB67. Immunological and biochemical characterization of pMB67 demonstrated that it: (i) contains a specific epitope, (ii) is not modified by lipid but does contain cysteine, (iii) does not contain a Vsp-like repetitive periodic protein structure, (iv) is a predominant antigen recognized during M. bovis infections, (v) undergoes a high rate of phase variation in vitro and (vi) is size-variable. These results showed that M. bovis employs two types of specialized membrane proteins for surface diversification. The pMB67 protein may be useful in diagnostic assays and as a vaccine component.

Animals↗
PubMed1986

Antigenic variation in the phase I lipopolysaccharide of Coxiella burnetii isolates.

Coxiella burnetii isolates from a variety of clinical and geographical sources were screened for antigenic variation of lipopolysaccharides (LPSs) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis coupled with silver staining or immunoblotting. All isolates from chronic Q fever or other sources possessed a phase I-type LPS. These LPSs appeared to fall into three groups based on the sodium dodecyl sulfate-polyacrylamide gel electrophoresis profile or on reactivity with rabbit anti-C. burnetti antisera. The LPS of one group was identified on isolates from milk, ticks, or primary Q fever. The two remaining groups were found almost exclusively on isolates from human cases of chronic Q fever.

Antigens, Bacterial↗
PubMed1993

Frameshifting and antigenic variation in respiratory syncytial virus.

Recent studies have suggested that frameshift mutations in the attachment protein gene of respiratory syncytial (RS) virus may contribute to its variability. Many pathogens use several mechanisms for antigenic variation to elude their hosts' immune responses, and the frameshift mechanism is not unique to RS virus. Indeed, it may turn out to be a widespread genetic phenomenon among pathogens.

Antigens, Viral↗
PubMed1997

Limited antigenic variation among recent infectious bursal disease virus isolates from France.

Seven neutralizing monoclonal antibodies (Mabs) to infectious bursal disease virus (IBDV) were used in an antigen-capture ELISA for the antigenic characterization of 58 IBDV isolates obtained in France since 1989. Fifty-six isolates exhibited an antigenic profile which was different from reference strain Faragher 52/70, and similar to French very virulent IBDV strain 89,163 (no binding of two Mabs). Two strains (3.4%), isolated in 1991 and 1994, showed additional antigenic modifications resulting in suppressed or reduced binding activity of three other Mabs. The two atypical viruses were not re-identified in field samples subsequently collected, hence showing that antigenic variants of IBDV do not tend to replace the antigenically dominant 89,163-like strains that have prevailed in France since 1989.

Animals↗
PubMed1986

Antigenic variation of gonococcal pilus involves assembly of separated silent gene segments.

The pilus is a major outer-membrane protein of Neisseria gonorrhoeae that undergoes phase and antigenic variation. In strain MS11 pilus expression is regulated at two expression loci on the chromosome, pilE1 and pilE2, although many other regions contain silent pilin information. A comparison of variant pilin sequences has revealed that the gene can be divided into a constant, a semivariable, and a hypervariable region. We report here that complete pilin genes are found only at the expression loci. Silent constant and variable region pilin gene segments are located on separate and distinct restriction fragments, and the generation of a complete pilin gene within the expression loci is the result of multiple recombination events. Conserved sequences within and flanking the pilin gene are proposed to act as recombination sites during the gene conversion events needed to produce a functional pilin gene.

Antigens, Bacterial↗
PubMed1987

Antigenic variation of porcine transmissible gastroenteritis virus detected by monoclonal antibodies.

Mouse myeloma cells (SP2/O) were fused with spleen cells from BALB/c mice immunized with detergent-solubilized antigen of purified virus, and 21 monoclonal (MC) antibodies reactive in enzyme-linked immunosorbent assay with the TO-163 strain of porcine transmissible gastroenteritis (TGE) virus were obtained. Of these MC antibodies, 14, 6 and 1 were IgG1, IgG2a and IgM, respectively. All of the MC antibodies contained light chains of the kappa type. Of these MC antibodies, 8 were found to have neutralization (NT) activity against the TO-163 strain. Comparison of 7 strains of TGE virus by NT tests using our panel of MC antibodies confirmed their close antigenic relationships, but also revealed the occurrence of distinct antigenic differences. These results suggest that there may be at least 6 different epitopes involved in NT reaction on the virion of the TO-163 strain. This notion was confirmed by the competitive binding assay.

Animals↗
PubMed1986

Antigenic variation in rabies virus strains.

Several rabies virus isolates from small wild rodents, one strain isolated from a fox and another from a cat, as well as the CVS strain were compared in cross-protection and virus-neutralization tests. Antigenic variations between the strains and between different batches of individual strains were found. These antigenic differences could not be explained by denaturation caused by UV irradiation or deep-freeze storage, by the presence of "incomplete" particles or by passage in immune organism. An antigenic difference was batch-specific and was only demonstrable on comparison with a relatively large number of strains: it has probably developed during the assembly of antigenic determinants of the virion. There was no correlation between protective and virus-neutralizing activities.

Animals↗