antigenic variation


Summary: Change in the surface ANTIGEN of a microorganism. There are two different types. One is a phenomenon, especially associated with INFLUENZA VIRUSES, where they undergo spontaneous variation both as slow antigenic drift and sudden emergence of new strains (antigenic shift). The second type is when certain PARASITES, especially trypanosomes, PLASMODIUM, and BORRELIA, survive the immune response of the host by changing the surface coat (antigen switching). (From Herbert et al., The Dictionary of Immunology, 4th ed)

Top Publications

  1. Povelones M, Gluenz E, Dembek M, Gull K, Rudenko G. Histone H1 plays a role in heterochromatin formation and VSG expression site silencing in Trypanosoma brucei. PLoS Pathog. 2012;8:e1003010 pubmed publisher
    The African sleeping sickness parasite Trypanosoma brucei evades the host immune system through antigenic variation of its variant surface glycoprotein (VSG) coat. Although the T...
  2. Bull P, Buckee C, Kyes S, Kortok M, Thathy V, Guyah B, et al. Plasmodium falciparum antigenic variation. Mapping mosaic var gene sequences onto a network of shared, highly polymorphic sequence blocks. Mol Microbiol. 2008;68:1519-34 pubmed publisher
  3. Xu R, Ekiert D, Krause J, Hai R, Crowe J, Wilson I. Structural basis of preexisting immunity to the 2009 H1N1 pandemic influenza virus. Science. 2010;328:357-60 pubmed publisher
    ..Thus, antigenic similarity between the 2009 and 1918-like viruses provides an explanation for the age-related immunity to the current influenza pandemic. ..
  4. Rosenberg E, Ben Shmuel A, Shalev O, Sinay R, Cowman A, Pollack Y. Differential, positional-dependent transcriptional response of antigenic variation (var) genes to biological stress in Plasmodium falciparum. PLoS ONE. 2009;4:e6991 pubmed publisher
    ..As disease severity is partly associated with expression of particular var gene subtypes, manipulation of the IE environment may serve as a mechanism to direct transcription towards less virulent genes. ..
  5. Hertz Fowler C, Figueiredo L, Quail M, Becker M, Jackson A, Bason N, et al. Telomeric expression sites are highly conserved in Trypanosoma brucei. PLoS ONE. 2008;3:e3527 pubmed publisher
    ..This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology.
  6. Prucca C, Lujan H. Antigenic variation in Giardia lamblia. Cell Microbiol. 2009;11:1706-15 pubmed publisher
    Giardia lamblia undergoes antigenic variation, both in vitro and within the intestines of infected individuals...
  7. Glover L, Alsford S, Horn D. DNA break site at fragile subtelomeres determines probability and mechanism of antigenic variation in African trypanosomes. PLoS Pathog. 2013;9:e1003260 pubmed publisher
    b>Antigenic variation in African trypanosomes requires monoallelic transcription and switching of variant surface glycoprotein (VSG) genes...
  8. Coutte L, Botkin D, Gao L, Norris S. Detailed analysis of sequence changes occurring during vlsE antigenic variation in the mouse model of Borrelia burgdorferi infection. PLoS Pathog. 2009;5:e1000293 pubmed publisher
    ..The vls antigenic variation system, which expresses the surface-exposed lipoprotein VlsE, plays a major role in B...
  9. Tonkin C, Carret C, Duraisingh M, Voss T, Ralph S, Hommel M, et al. Sir2 paralogues cooperate to regulate virulence genes and antigenic variation in Plasmodium falciparum. PLoS Biol. 2009;7:e84 pubmed publisher
    ..1 (PfEMP1) molecules displayed on the erythrocyte surface are responsible for cytoadherance and undergo antigenic variation in the course of an infection...

More Information


  1. DuBois K, Alsford S, Holden J, Buisson J, Swiderski M, Bart J, et al. NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions. PLoS Biol. 2012;10:e1001287 pubmed publisher
    ..NUP-1 depletion leads to increased VSG switching and therefore appears to have a role in control of antigenic variation. Thus, analogous to vertebrate lamins, NUP-1 is a major component of the nucleoskeleton with key roles in ..
  2. Horn D, McCulloch R. Molecular mechanisms underlying the control of antigenic variation in African trypanosomes. Curr Opin Microbiol. 2010;13:700-5 pubmed publisher
    ..We describe the factors and sequences recently linked to mutually exclusive transcription and VSG recombination, and how these act in the control of the key virulence mechanism of antigenic variation.
  3. Fouchier R, Smith D. Use of antigenic cartography in vaccine seed strain selection. Avian Dis. 2010;54:220-3 pubmed
    ..Until recently, antigenic variation was not considered a serious issue with influenza vaccines for poultry...
  4. Yang J, Lin C, Chen C, Liu J, Huang Y, Kuo C, et al. A new antigenic variant of human influenza A (H3N2) virus isolated from airport and community surveillance in Taiwan in early 2009. Virus Res. 2010;151:33-8 pubmed publisher
  5. Noble R, Recker M. A statistically rigorous method for determining antigenic switching networks. PLoS ONE. 2012;7:e39335 pubmed publisher
    Many vector-borne pathogens rely on antigenic variation to prolong infections and increase their likelihood of onward transmission...
  6. Dzikowski R, Deitsch K. Genetics of antigenic variation in Plasmodium falciparum. Curr Genet. 2009;55:103-10 pubmed publisher antigenic proteins that that are vulnerable to antibody recognition and attack, a process called antigenic variation. Significant work in recent years has contributed to our understanding of the mechanisms underlying this ..
  7. Prucca C, Slavin I, Quiroga R, Elias E, Rivero F, Saura A, et al. Antigenic variation in Giardia lamblia is regulated by RNA interference. Nature. 2008;456:750-4 pubmed publisher
    ..To evade the host's immune response, Giardia undergoes antigenic variation-a process that allows the parasite to develop chronic and recurrent infections...
  8. Killoran M, Kohler P, Dillard J, Keck J. RecQ DNA helicase HRDC domains are critical determinants in Neisseria gonorrhoeae pilin antigenic variation and DNA repair. Mol Microbiol. 2009;71:158-71 pubmed publisher
    Neisseria gonorrhoeae (Gc), an obligate human bacterial pathogen, utilizes pilin antigenic variation to evade host immune defences...
  9. Palmer G, Brayton K. Antigenic variation and transmission fitness as drivers of bacterial strain structure. Cell Microbiol. 2013;15:1969-75 pubmed publisher
  10. Hayes C, Diez D, Joannin N, Honda W, Kanehisa M, Wahlgren M, et al. varDB: a pathogen-specific sequence database of protein families involved in antigenic variation. Bioinformatics. 2008;24:2564-5 pubmed publisher
    ..b>Antigenic variation and drift are mechanisms by which pathogens change their exposed epitopes while maintaining protein ..
  11. Gjini E, Haydon D, Barry J, Cobbold C. The impact of mutation and gene conversion on the local diversification of antigen genes in African trypanosomes. Mol Biol Evol. 2012;29:3321-31 pubmed publisher
    ..diversity in parasite antigen gene families hold important information about their potential to generate antigenic variation within and between hosts...
  12. Dobson R, Stockdale C, Lapsley C, Wilkes J, McCulloch R. Interactions among Trypanosoma brucei RAD51 paralogues in DNA repair and antigenic variation. Mol Microbiol. 2011;81:434-56 pubmed publisher used for moving variant surface glycoprotein (VSG) genes into expression sites during immune evasion by antigenic variation. A major route for such VSG switching is gene conversion reactions in which RAD51, a universally conserved ..
  13. Blyuss K, Gupta S. Stability and bifurcations in a model of antigenic variation in malaria. J Math Biol. 2009;58:923-37 pubmed publisher
    We examine the properties of a recently proposed model for antigenic variation in malaria which incorporates multiple epitopes and both long-lasting and transient immune responses...
  14. Guizetti J, Scherf A. Silence, activate, poise and switch! Mechanisms of antigenic variation in Plasmodium falciparum. Cell Microbiol. 2013;15:718-26 pubmed publisher
    Phenotypic variation in genetically identical malaria parasites is an emerging topic. Although antigenic variation is only part of a more global parasite strategy to create adaptation through epigenetically controlled transcriptional ..
  15. Zimmerman C, Stiedl T, Rosengarten R, Spergser J. Alternate phase variation in expression of two major surface membrane proteins (MBA and UU376) of Ureaplasma parvum serovar 3. FEMS Microbiol Lett. 2009;292:187-93 pubmed publisher
    ..We propose that in U. parvum serovar 3, and presumably in all U. parvum and U. urealyticum, an inversion event at specific sites effects an alternate ON/OFF switching of the genes UU375 and UU376. ..
  16. Upadhyaya S, Ayelet G, Paul G, King D, Paton D, Mahapatra M. Genetic basis of antigenic variation in foot-and-mouth disease serotype A viruses from the Middle East. Vaccine. 2014;32:631-8 pubmed publisher
    ..Comparisons of capsid sequences identified substitutions in neutralising antigenic sites (1, 2 and 4), which either individually or together underpin these observed antigenic phenotypes. ..
  17. Citti C, Nouvel L, Baranowski E. Phase and antigenic variation in mycoplasmas. Future Microbiol. 2010;5:1073-85 pubmed publisher
  18. Kim H, Cross G. TOPO3alpha influences antigenic variation by monitoring expression-site-associated VSG switching in Trypanosoma brucei. PLoS Pathog. 2010;6:e1000992 pubmed publisher
    Homologous recombination (HR) mediates one of the major mechanisms of trypanosome antigenic variation by placing a different variant surface glycoprotein (VSG) gene under the control of the active expression site (ES)...
  19. Giacani L, Brandt S, Puray Chavez M, Reid T, Godornes C, Molini B, et al. Comparative investigation of the genomic regions involved in antigenic variation of the TprK antigen among treponemal species, subspecies, and strains. J Bacteriol. 2012;194:4208-25 pubmed publisher
    ..Although each of the above-mentioned species and subspecies has a functional tprK antigenic variation system, it is still unclear why the level of expression and the rate at which tprK diversifies during ..
  20. Rivero F, Saura A, Prucca C, Carranza P, Torri A, Lujan H. Disruption of antigenic variation is crucial for effective parasite vaccine. Nat Med. 2010;16:551-7, 1p following 557 pubmed publisher
    Giardia lamblia is a human intestinal pathogen. Like many protozoan microorganisms, Giardia undergoes antigenic variation, a mechanism assumed to allow parasites to evade the host's immune response, producing chronic and/or recurrent ..
  21. Cunningham D, Lawton J, Jarra W, Preiser P, Langhorne J. The pir multigene family of Plasmodium: antigenic variation and beyond. Mol Biochem Parasitol. 2010;170:65-73 pubmed publisher
    ..erythrocytes, and therefore could be potential targets of the host's immune response, and involved in antigenic variation and immune evasion. Other functions such as signalling, trafficking and adhesion have been also postulated...
  22. La Greca F, Magez S. Vaccination against trypanosomiasis: can it be done or is the trypanosome truly the ultimate immune destroyer and escape artist?. Hum Vaccin. 2011;7:1225-33 pubmed publisher
  23. Brancucci N, Witmer K, Schmid C, Flueck C, Voss T. Identification of a cis-acting DNA-protein interaction implicated in singular var gene choice in Plasmodium falciparum. Cell Microbiol. 2012;14:1836-48 pubmed publisher
    Plasmodium falciparum is responsible for the most severe form of malaria in humans. Antigenic variation of P...
  24. Lindesmith L, Debbink K, Swanstrom J, Vinje J, Costantini V, Baric R, et al. Monoclonal antibody-based antigenic mapping of norovirus GII.4-2002. J Virol. 2012;86:873-83 pubmed publisher
    ..Surrogate neutralization assays using sera and mouse monoclonal antibodies (MAbs) suggest that antigenic variation maintains GII...
  25. Hensley S, Das S, Gibbs J, Bailey A, Schmidt L, Bennink J, et al. Influenza A virus hemagglutinin antibody escape promotes neuraminidase antigenic variation and drug resistance. PLoS ONE. 2011;6:e15190 pubmed publisher
    ..Here, we show that antibody-driven antigenic variation in one domain of the H1 hemagglutinin Sa site leads to compensatory mutations in NA, resulting in NA ..
  26. Takemae N, Nguyen T, Ngo L, Hiromoto Y, Uchida Y, Pham V, et al. Antigenic variation of H1N1, H1N2 and H3N2 swine influenza viruses in Japan and Vietnam. Arch Virol. 2013;158:859-76 pubmed publisher
    ..Minor antigenic variation between pig A(H1N1)pdm09 viruses was evident by HI assay using 13 mAbs raised against homologous virus...
  27. Lindesmith L, Donaldson E, Baric R. Norovirus GII.4 strain antigenic variation. J Virol. 2011;85:231-42 pubmed publisher
    ..assays using sera from outbreaks and from immunized mice suggest that, as with influenza virus, antigenic variation maintains GII.4 persistence in the face of human population herd immunity...
  28. Kang K, Yamamura Y, Carlos M, Karvelas N, Kim I, Sunkara D, et al. Synthetic antigens representing the antigenic variation of human hepatitis C virus. Viral Immunol. 2010;23:497-508 pubmed publisher
    ..infecting patients, we decided to design peptide combinations that represent the theoretical maximum antigenic variation of each epitope to be used as capture antigens...
  29. Helm R, Seifert H. Frequency and rate of pilin antigenic variation of Neisseria meningitidis. J Bacteriol. 2010;192:3822-3 pubmed publisher
    The rates of pilin antigenic variation (Av) of two strains of Neisseria meningitidis were determined using an unbiased DNA sequencing assay. Strain MC58 underwent pilin Av at a rate similar to that of N...
  30. Harrison L, Shutt K, Schmink S, Marsh J, Harcourt B, Wang X, et al. Population structure and capsular switching of invasive Neisseria meningitidis isolates in the pre-meningococcal conjugate vaccine era--United States, 2000-2005. J Infect Dis. 2010;201:1208-24 pubmed publisher
    ..The high prevalence of capsular switching requires surveillance to detect changes in the meningococcal population structure that may affect the effectiveness of meningococcal vaccines. ..
  31. Carranza P, Lujan H. New insights regarding the biology of Giardia lamblia. Microbes Infect. 2010;12:71-80 pubmed publisher
    ..findings regarding the process of Giardia trophozoites differentiation into infective cysts as well as the mechanism of antigenic variation, which allows the parasite to cause chronic and recurrent infections in susceptible individuals.
  32. Cahoon L, Seifert H. An alternative DNA structure is necessary for pilin antigenic variation in Neisseria gonorrhoeae. Science. 2009;325:764-7 pubmed publisher
    Pathogens can use DNA recombination to promote antigenic variation (Av) of surface structures to avoid immune detection...
  33. Gog J. The impact of evolutionary constraints on influenza dynamics. Vaccine. 2008;26 Suppl 3:C15-24 pubmed
    ..These can occur for the same parameter values: a bistable system where it is possible to switch between these behaviours. This raises some important prospects for vaccination strategies, particularly pausing influenza drift. ..
  34. Khattab A, Bonow I, Schreiber N, Petter M, Schmetz C, Klinkert M. Plasmodium falciparum variant STEVOR antigens are expressed in merozoites and possibly associated with erythrocyte invasion. Malar J. 2008;7:137 pubmed publisher
    ..Their abundance and hypervariability support a role in antigenic variation. Immunoblotting of total parasite proteins with an anti-STEVOR antibody was used to identify variant ..
  35. Frank M, KIRKMAN L, Costantini D, Sanyal S, Lavazec C, Templeton T, et al. Frequent recombination events generate diversity within the multi-copy variant antigen gene families of Plasmodium falciparum. Int J Parasitol. 2008;38:1099-109 pubmed publisher
    The human malaria parasite Plasmodium falciparum utilises a mechanism of antigenic variation to avoid the antibody response of its human host and thereby generates a long-term, persistent infection...
  36. Russell C, Jones T, Barr I, Cox N, Garten R, Gregory V, et al. The global circulation of seasonal influenza A (H3N2) viruses. Science. 2008;320:340-6 pubmed publisher
  37. Ueti M, Tan Y, Broschat S, Castañeda Ortiz E, Camacho Nuez M, Mosqueda J, et al. Expansion of variant diversity associated with a high prevalence of pathogen strain superinfection under conditions of natural transmission. Infect Immun. 2012;80:2354-60 pubmed publisher
    ..The results of the present study, which examined strain structure under conditions of natural transmission and population immunity, support that high levels of endemicity also drive pathogen divergence toward greater strain diversity...
  38. Bedford T, Rambaut A, Pascual M. Canalization of the evolutionary trajectory of the human influenza virus. BMC Biol. 2012;10:38 pubmed publisher
    ..In the model, the influenza population shows a 1- to 2-year timescale of repeatability, suggesting a window in which evolutionary dynamics could be, in theory, predictable. ..
  39. Jackson A, Berry A, Aslett M, Allison H, Burton P, Vavrova Anderson J, et al. Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species. Proc Natl Acad Sci U S A. 2012;109:3416-21 pubmed publisher
    b>Antigenic variation enables pathogens to avoid the host immune response by continual switching of surface proteins...
  40. Wang X, Xiao Y, Bouchut A, Al Khedery B, Wang H, Allred D. Characterization of the unusual bidirectional ves promoters driving VESA1 expression and associated with antigenic variation in Babesia bovis. Eukaryot Cell. 2012;11:260-9 pubmed publisher
    Rapid clonal antigenic variation in Babesia bovis involves the variant erythrocyte surface antigen-1 (VESA1) protein expressed on the infected-erythrocyte surface...
  41. Magez S, Caljon G, Tran T, Stijlemans B, Radwanska M. Current status of vaccination against African trypanosomiasis. Parasitology. 2010;137:2017-27 pubmed publisher
    ..While antigenic variation of the parasite surface coat has been considered the major obstacle in the development of a functional ..
  42. Helm R, Seifert H. Pilin antigenic variation occurs independently of the RecBCD pathway in Neisseria gonorrhoeae. J Bacteriol. 2009;191:5613-21 pubmed publisher
    ..In Neisseria, these pili undergo frequent antigenic variation (Av), which is presumed to allow reinfection of high-risk groups...
  43. Lindesmith L, Beltramello M, Donaldson E, Corti D, Swanstrom J, Debbink K, et al. Immunogenetic mechanisms driving norovirus GII.4 antigenic variation. PLoS Pathog. 2012;8:e1002705 pubmed publisher
    ..Moreover, these data support the hypothesis that GII.4 norovirus evolution is heavily influenced by antigenic variation of neutralizing epitopes and consequently, antibody-driven receptor switching; thus, protective herd ..
  44. Burgos R, Wood G, Young L, Glass J, Totten P. RecA mediates MgpB and MgpC phase and antigenic variation in Mycoplasma genitalium, but plays a minor role in DNA repair. Mol Microbiol. 2012;85:669-83 pubmed publisher
    ..genitalium, a sexually transmitted human pathogen, encodes MgpB and MgpC adhesins that undergo phase and antigenic variation through recombination with archived 'MgPar' donor sequences...
  45. Volz J, Bartfai R, Petter M, Langer C, Josling G, Tsuboi T, et al. PfSET10, a Plasmodium falciparum methyltransferase, maintains the active var gene in a poised state during parasite division. Cell Host Microbe. 2012;11:7-18 pubmed publisher
    ..switched expression of one of 60 var genes encoding PfEMP1 in each parasite genome provides a mechanism for antigenic variation. We report the identification of a parasite protein, designated PfSET10, which localizes exclusively to the ..
  46. Lannergård J, Gustafsson M, Waldemarsson J, Norrby Teglund A, Stålhammar Carlemalm M, Lindahl G. The Hypervariable region of Streptococcus pyogenes M protein escapes antibody attack by antigenic variation and weak immunogenicity. Cell Host Microbe. 2011;10:147-57 pubmed publisher
    ..These data indicate that the M protein HVR evades antibody attack not only through antigenic variation but also by weak immunogenicity, a paradoxical observation that may apply to other HVR-containing proteins.
  47. Janes J, Wang C, Levin Edens E, Vigan Womas I, Guillotte M, Melcher M, et al. Investigating the host binding signature on the Plasmodium falciparum PfEMP1 protein family. PLoS Pathog. 2011;7:e1002032 pubmed publisher
    The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family plays a central role in antigenic variation and cytoadhesion of P. falciparum infected erythrocytes...
  48. Koelle K, Kamradt M, Pascual M. Understanding the dynamics of rapidly evolving pathogens through modeling the tempo of antigenic change: influenza as a case study. Epidemics. 2009;1:129-37 pubmed publisher
    ..These advantages of the antigenic tempo model make it a useful alternative to address several outstanding questions for rapidly evolving pathogens. ..
  49. Li Z, Li Y, Chang S, Ding Z, Mu L, Cong Y. Antigenic variation between Newcastle disease viruses of goose and chicken origin. Arch Virol. 2010;155:499-505 pubmed publisher
    ..The results indicated that antigenic variation had occurred between NDV/NA-1 strains and NDV/F48E9, F48E8 strains...
  50. Cahoon L, Manthei K, Rotman E, Keck J, Seifert H. Neisseria gonorrhoeae RecQ helicase HRDC domains are essential for efficient binding and unwinding of the pilE guanine quartet structure required for pilin antigenic variation. J Bacteriol. 2013;195:2255-61 pubmed publisher
    ..For pilin antigenic variation (Av) to occur, a guanine quartet (G4) structure must form upstream of pilE...
  51. Scherf A, Lopez Rubio J, Rivière L. Antigenic variation in Plasmodium falciparum. Annu Rev Microbiol. 2008;62:445-70 pubmed publisher
    ..b>Antigenic variation is orchestrated by epigenetic factors including monoallelic var transcription at separate spatial domains ..
  52. Ping J, Li C, Deng G, Jiang Y, Tian G, Zhang S, et al. Single-amino-acid mutation in the HA alters the recognition of H9N2 influenza virus by a monoclonal antibody. Biochem Biophys Res Commun. 2008;371:168-71 pubmed publisher
    We explored the molecular basis of antigenic variation by comparing two H9N2 subtype avian influenza viruses, A/Chicken/Shandong/6/96 (CK/SD/6) and A/Chicken/Guangxi/10/99 (CK/GX/10), that react differently to a monoclonal antibody C/B3...
  53. Ludi A, Horton D, Li Y, Mahapatra M, King D, Knowles N, et al. Antigenic variation of foot-and-mouth disease virus serotype A. J Gen Virol. 2014;95:384-92 pubmed publisher