539:
538:
285:
switched cells because initial VSGs remain targets for the escalating host Ab response. Mosaic VSG genes can be created by homologous recombination of a partial VSG gene from an array. This partial gene may replace any portion of the residing VSG gene, creating a new mosaic VSG. VSG half-life measurements suggest that initial VSGs may persist on the surface of genetically switched trypanosomes for several days. It remains unclear whether the regulation of VSG switching is purely stochastic or whether environmental stimuli affect switching frequency. The fact that switching occurs in vitro suggests that there is at least some host-independent, stochastic element to the process.
292:. The cyclical process take 5β8 days. This occurs because a diverse range of coats expressed by the trypanosome population means that the immune system is always one step behind: it takes several days for an immune response against a given VSG to develop, giving the population time to diversify as individuals undergo further switching events. The repetition of this process prevents the extinction of the infecting trypanosome population, allowing chronic persistence of parasites in the host and enhancing opportunities for transmission.
543:
into an ES, where it replaces the active VSG. C. Telomeric VSG conversion: A telomeric VSG (including 70 bp repeat sequence upstream and telomere downstream) replaces the active VSG in the ES D. Segmental VSG conversion: Sequence is copied from multiple inactive VSG genes and combined into a novel mosaic VSG that occupies the ES E. Transcriptional VSG switching: A non-recombination based mechanism that activates a new (previously silent) ES, while inactivating the previously active ES.
673:βa noncovalent linkage from the C-terminus which directs its forward trafficking from the ER to the membrane. This GPI anchor is specifically cleaved by GPI Phospholipase C, cleaving the membrane-form VSG, and allowing VSG protein and portion of the GPI anchor to be lost into the extracellular milieu as soluble VSG (sVSG, which is can be recognized as Cross-Reacting Determinant, or CRD), while retaining the two 1,2-dimyristolglycerol chains in the membrane.
225:. They form a 12β15 nm surface coat. VSG dimers make up ~90% of all cell surface protein and ~10% of total cell protein. For this reason, these proteins are highly immunogenic and an immune response raised against a specific VSG coat will rapidly kill trypanosomes expressing this variant. However, with each cell division there is a possibility that the progeny will switch expression to change the VSG that is being expressed. VSG has no prescribed
736:
response against a given VSG to develop, giving the population time to diversify as individuals undergo further switching events. Reiteration of this process prevents extinction of the infecting trypanosome population, allowing chronic persistence of parasites in the host, enhancing opportunities for transmission. The clinical effect of this cycle is successive 'waves' of parasitaemia (trypanosomes in the blood).
233:
677:
622:), where it is transiently monoglucosylated and deglucosylated, and interacts with various ER chaperone proteins, such as BiP, in order to fold correctly. VSG efficiently folds and dimerizes (suggesting intrinsically favorable folding) and is transported through the Golgi to the flagellar pocket for incorporation into the cell membrane.
625:
Importantly, following incorporation into the cellular membrane, VSG may later be recycled through the flagellar pocket and sorted back to the cell surface. VSG is not turned over by lysosomal or proteasomal canonical degradation pathways, but is instead lost from the cell by specific cleavage of its
542:
Mechanisms of VSG switching in T. brucei: A. Structure of the expression site including the expression site associated genes (ESAG), 70 base pair repeat up-stream sequence, expressed VSG gene, and the telomere B. Mechanism of array VSG conversion: A silent VSG is copied from a subtelomeric VSG array
763:
in horses, These proteins allow the parasite to efficiently evade the host animal's immune system. These VSGs allow the organism to constantly manipulate and change the surface structure of its proteins, which means it is constantly being presented to the immune system as a new foreign organism and
485:
gene in the active site to a different variant. The genome contains many copies of VSG genes, both on minichromosomes and in repeated sections in the interior of the chromosomes. These are generally silent, typically with omitted sections or premature stop codons, but are important in the evolution
284:
of a silent basic copy gene from an array (directed by homology) into the active telomerically-located expression site. During this transition, trypanosomes simultaneously display both pre- and post-switch VSGs on their surface. This coat replacement process is critical for the survival of recently
680:
Structure of one of the N-terminal VSG variants. VSG genes have a largely conserved N-terminal secondary and tertiary structure (composed of two alpha-helices which form the dimerization interface, and which couple into a four helix bundle), while still allowing for variable primary sequence. This
735:
populations can peak at a size of 10 within a host this rapid rate of switching ensures that the parasite population is constantly diverse. A diverse range of coats expressed by the trypanosome population means that the immune system is always one step behind: it takes several days for an immune
473:
of some of the large and intermediate chromosomes. Each ES is a polycistronic unit, containing a number of
Expression Site-Associated Genes (ESAGs) all expressed along with the active VSG. While multiple ES exist, only a single one is ever active at one time. A number of mechanisms appear to be
356:
Antigen 'cleaning' and VSG recyclingβVSG is efficiently recycled through the trypanosome flagellar pocket, allowing antibodies to be 'cleaned' from VSG before re-incorporation back into the cellular membrane. Importantly, VSGs recognized and bound by antibodies are selectively pushed toward the
1507:
Hertz-Fowler C, Figueiredo LM, Quail MA, Becker M, Jackson A, Bason N, Brooks K, Churcher C, Fahkro S, Goodhead I, Heath P, Kartvelishvili M, Mungall K, Harris D, Hauser H, Sanders M, Saunders D, Seeger K, Sharp S, Taylor JE, Walker D, White B, Young R, Cross GA, Rudenko G, Barry JD, Louis EJ,
661:
domain of ~100 amino acids. N-terminal domains are grouped into classes A-C depending on their cysteine patterns. C-term domains are grouped by sequence homology into classes I-III, with apparently no restriction on which N-term classes they can pair with to form a full VSG. To dimerize, VSG
845:
are utilized in the biosynthesis of the carbohydrate moiety directly whereas galactose was converted possibly to other intermediates before being incorporated into the antigen. The unglycosylated VSG with a molecular weight of 47 kDa had completely lost its size heterogeneity.
646:(tertiary) features, based on two determined 3-dimensional structures and conservation of 2-dimensional sequence motifs (descending and ascending alpha-helices that make up the dimerization interface), allowing them to perform a similar shielding function. VSGs are made up of
602:
reaction (removing of the C-term hydrophobic 17 or 23 aa GPI anchoring sequence). The Ο site is always Ser (usually in 17 aa signal sequence peptides), Asp (usually in 23 aa signal sequence peptides), or Asn. Also, the number of
513:. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of
2118:
Sengupta PP, Balumahendiran M, Balamurugan V, Rudramurthy GR, Prabhudas K (June 2012). "Expressed truncated N-terminal variable surface glycoprotein (VSG) of
Trypanosoma evansi in E. coli exhibits immuno-reactivity".
726:
will switch expression to change the VSG that is being expressed. The frequency of VSG switching has been measured to be approximately 0.1% per division, though switching rates do differ in culture vs.
240:
cell membrane is densely packed with VSG dimers, which make up ~90% of its cell surface protein, and which allows for the parasite to evade the immune system and establish chronic infection.
1829:
Freymann D, Down J, Carrington M, Roditi I, Turner M, Wiley D (1990). "2.9 Γ
resolution structure of the N-terminal domain of a variant surface glycoprotein from
Trypanosoma brucei".
357:
flagellar pocket at a quicker rate than unidentified VSG; in this scenario, the antibody acts as a 'sail', which quickens the process of VSG being brought to the area of recycling.
1326:"Analysis of the VSG gene silent archive in Trypanosoma brucei reveals that mosaic gene expression is prominent in antigenic variation and is favored by archive substructure"
1745:
Mehlert A, Bond CS, Ferguson MA (October 2002). "The glycoforms of a
Trypanosoma brucei variant surface glycoprotein and molecular modeling of a glycosylated surface coat".
768:
is a very efficient organism; it may infect fewer species than other diseases, but it infects and survives very efficiently within its specified hosts. The VSG proteins in
338:
etc.). The coat is uniform, made up of millions of copies of the same molecule; therefore, VSG is the only part of the trypanosome that the immune system can recognize.
2205:
Gardiner PR, Nene V, Barry MM, Thatthi R, Burleigh B, Clarke MW (November 1996). "Characterization of a small variable surface glycoprotein from
Trypanosoma vivax".
509:
The bloodstream expression site (BES), or telomeric expression site, is used for exchanging variant surface glycoproteins when in host's blood stream to escape the
1864:
Blum ML, Down JA, Gurnett AM, Carrington M, Turner MJ, Wiley DC (April 1993). "A structural motif in the variant surface glycoproteins of
Trypanosoma brucei".
373:), which directs its forward-trafficking from the ER to the flagellar pocket for incorporation into the membrane, as predicted by the GPI valence hypothesis.
91:
900:
Cross GA (1975). "Identification, purification and properties of clone-specific glycoprotein antigens constituting the surface coat of
Trypanosoma brucei".
447:
archive, and can contribute directly to antigenic variation, vastly increasing the trypanosome's capacity for immune evasion and posing a major problem for
1567:
Vanhamme L, Lecordier L, Pays E (May 2001). "Control and function of the bloodstream variant surface glycoprotein expression sites in
Trypanosoma brucei".
318:
Shielding β the dense nature of the VSG coat (VSG proteins pack shoulder-to-shoulder) prevents the immune system of the mammalian host from accessing the
943:
Buck GA, Jacquemot C, Baltz T, Eisen H (December 1984). "Re-expression of an inactivated variable surface glycoprotein gene in
Trypanosoma equiperdum".
590:, and the appearance of the N-terminal signal sequence directs VSG to the ER. VSG is thereby co-translationally transported into the ER lumen, rapidly
280:(Tfr: ESAG6, ESAG7) is one. Only one VSG gene is expressed at a time, as only one of the ~15 ES are active in a cell. VSG expression is 'switched' by
1702:
Young JR, Turner MJ, Williams RO (1984). "The role of duplication in the expression of a variable surface glycoprotein gene of
Trypanosoma brucei".
353:
raised against the previous coat. This antigenic variation creates cyclical waves of parasitemia characteristic of Human African Trypanosomiasis.
1240:
Schwartz KJ, Peck RF, Tazeh NN, Bangs JD (December 2005). "GPI valence and the fate of secretory membrane proteins in African trypanosomes".
1042:
Overath P, Chaudhri M, Steverding D, Ziegelbauer K (February 1994). "Invariant surface proteins in bloodstream forms of Trypanosoma brucei".
998:
2240:
Reinwald E, Heidrich C, Risse HJ (May 1984). "In vitro studies on the biosynthesis of the surface glycoprotein of Trypanosoma congolense".
799:
with all the sera combinations. The animals immunized with whole cell lysate or recombinant protein show similar antibody reactions in
1915:
Turner CM (August 1997). "The rate of antigenic variation in fly-transmitted and syringe-passaged infections of Trypanosoma brucei".
517:(ESAGs). There is a collection of an estimated 20-30 sites, each being active at a time. Active VSG expression sites are depleted of
1162:
666:
directed by hydrophobic interactions, around which hang smaller structural features (five smaller helices and three beta-sheets).
881:
876:
535:
have been classified into two groups depending upon whether or not duplication of the genes is observed when they are expressed.
73:
2351:
583:
2156:"Variable Surface Glycoprotein RoTat 1.2 PCR as a specific diagnostic tool for the detection of Trypanosoma evansi infections"
981:
Barry JD, McCulloch R (2001). "Antigenic variation in trypanosomes: enhanced phenotypic variation in a eukaryotic parasite".
1163:"Localization of a Variable Surface Glycoprotein Phosphatidylinositol-Specific Phospholipase-C in Trypanosoma brucei brucei"
607:
sites per VSG may vary (usually 1-3 N-glycans). VSG MITat.1.5 is glycosylated at all three potential N-glycosylation sites.
419:, or fragmentation). Expression of an antigenically different VSG can occur by simply switching to a different full-length
861:
366:
289:
2361:
2326:
681:
variable primary sequence allows for VSG to be antigenically distinct from one another, the crux to antigenic variation.
654:
595:
611:
384:
midgut. There is a very fast inhibition of VSG gene transcription which occurs as soon as the temperature is lowered.
586:
is important for its RNA stability (most importantly, the 8mer and 14mer). VSG is then transcribed on membrane-bound
477:
The expressed VSG can be switched either by activating a different expression site (and thus changing to express the
808:
670:
2330:
871:
503:
281:
244:
The parasite has a large cellular repertoire of antigenically distinct VSGs (~1500/2000 complete and partial (
117:
44:
1653:"Variant Surface Glycoprotein gene repertoires in Trypanosoma brucei have diverged to become strain-specific"
764:
this prevents the body from mounting a large enough immune response to eradicate the disease. In this sense,
804:
498:
for expression. Again, the exact mechanisms that control this are unclear, but the process seems to rely on
1277:"Trypanosoma brucei: posttranscriptional control of the variable surface glycoprotein gene expression site"
2356:
829:
755:
591:
556:
495:
2023:
1963:
1873:
1521:
579:
412:
331:
308:
288:
The antigenic variation causes cyclical waves of parasitemia, which is one of the characteristics of
277:
265:
1193:"Glycosylphosphatidylinositol-dependent protein trafficking in bloodstream stage Trypanosoma brucei"
342:
273:
222:
221:. VSG allows the trypanosomatid parasites to evade the mammalian host's immune system by extensive
1897:
1727:
1489:
1016:
925:
781:
218:
213:
1459:"Antigenic variation in the African trypanosome: molecular mechanisms and phenotypic complexity"
1126:
Rudenko G (2011-10-24). "African trypanosomes: the genome and adaptations for immune evasion".
2306:
2257:
2222:
2187:
2136:
2100:
2051:
1989:
1932:
1889:
1846:
1811:
1762:
1719:
1684:
1633:
1584:
1549:
1481:
1439:
1404:
1355:
1306:
1257:
1222:
1143:
1108:
1059:
1004:
994:
960:
917:
820:
760:
709:
695:
643:
510:
350:
17:
855:
2296:
2288:
2249:
2214:
2177:
2167:
2128:
2090:
2082:
2041:
2031:
1979:
1971:
1924:
1881:
1838:
1801:
1793:
1754:
1711:
1674:
1664:
1651:
Hutchinson OC, Picozzi K, Jones NG, Mott H, Sharma R, Welburn SC, Carrington M (July 2007).
1623:
1615:
1576:
1539:
1529:
1473:
1431:
1394:
1386:
1345:
1337:
1296:
1288:
1249:
1212:
1204:
1135:
1098:
1090:
1079:"A Case of Sleeping Sickness showing Regular Periodical Increase of the Parasites Disclosed"
1051:
986:
952:
909:
791:
466:
269:
698:
raised against a specific VSG coat will rapidly kill trypanosomes expressing this variant.
349:
genetic modificationβ'switching'βallowing variants expressing a new VSG coat to escape the
1028:
627:
604:
571:
564:
165:
2027:
1967:
1877:
1525:
2301:
2276:
2253:
2086:
1984:
1951:
1928:
1806:
1781:
1679:
1652:
1628:
1603:
1544:
1509:
1422:
Pays E (November 2005). "Regulation of antigen gene expression in Trypanosoma brucei".
1399:
1374:
1350:
1325:
1170:
1103:
1078:
796:
773:
650:
639:
599:
575:
458:
261:
211:. This genus is notable for their cell surface proteins. They were first isolated from
2182:
2155:
2095:
2070:
2046:
2011:
2010:
Raibaud A, Gaillard C, Longacre S, Hibner U, Buck G, Bernardi G, Eisen H (July 1983).
1842:
1580:
1301:
1276:
1217:
1192:
990:
2345:
2336:
2218:
2154:
Claes F, Radwanska M, Urakawa T, Majiwa PA, Goddeeris B, BΓΌscher P (September 2004).
1975:
1477:
1055:
956:
837:
analyses of the incorporated sugars after hydrolysis of the glycoprotein showed that
719:
570:
VSG is first transcribed as a polycistron and then undergoes trypanosomatid-specific
424:
335:
319:
195:
1493:
929:
2069:
Baltz T, Giroud C, Baltz D, Duvillier G, Degand P, Demaille J, Pautrizel R (1982).
1901:
327:
253:
226:
474:
involved in this process, but the exact nature of the silencing is still unclear.
232:
2132:
2071:"The variable surface glycoproteins of Trypanosoma equiperdum are phosphorylated"
1731:
1534:
2012:"Genomic environment of variant surface antigen genes of Trypanosoma equiperdum"
838:
746:
691:
663:
491:
423:
gene by Expression Site switching (switching which ES is active). In addition,
416:
207:
175:
2016:
Proceedings of the National Academy of Sciences of the United States of America
1604:"Active VSG expression sites in Trypanosoma brucei are depleted of nucleosomes"
465:
is always located in an Expression Site (ES), which are specialised expression
1208:
913:
866:
658:
647:
518:
499:
408:
381:
346:
257:
245:
202:
141:
85:
1435:
2292:
2277:"The evolution of amastin surface glycoproteins in trypanosomatid parasites"
2036:
1758:
1669:
1094:
858:, another surface (trans-membrane) glycoprotein in trypanosomatid parasites
723:
470:
377:
2310:
2191:
2140:
1993:
1815:
1766:
1688:
1637:
1588:
1553:
1485:
1458:
1443:
1408:
1390:
1359:
1261:
1226:
1147:
1112:
1063:
1008:
818:
The smallest VSG protein (40 kDa in size) to date (1996) has been found in
2261:
2226:
2172:
2104:
2055:
1936:
1893:
1850:
1723:
1715:
1310:
1169:. Food and Agricultural Organization of the United Nations. Archived from
964:
676:
555:
have a simple, polarized membrane transport system consisting of a single
1292:
704:
699:
615:
587:
560:
323:
249:
199:
146:
1619:
264:). VSGs are expressed from a bloodstream expression site (BES, ES) in a
1510:"Telomeric expression sites are highly conserved in Trypanosoma brucei"
1341:
1139:
842:
448:
431:
genes can be generated by combining segments from more than one silent
392:
The source of VSG variability during infection is a large 'archive' of
370:
1797:
1782:"Surface proteins, ERAD and antigenic variation in Trypanosoma brucei"
1253:
921:
1885:
642:(primary) level, but variants are thought to have strongly conserved
400:
365:
are attached to the plasma membrane via a covalent attachment to two
68:
1275:
Pays E, Coquelet H, Pays A, Tebabi P, Steinert M (September 1989).
657:
with low sequence homology (13β30% identity), and a more conserved
311:, ~90% of all cell surface protein and ~10% of total cell protein.
800:
786:
715:
712:
675:
404:
231:
380:
when the parasite differentiates into the procyclic form in the
811:
can be used as a specific diagnostic tool for the detection of
314:
The properties of the VSG coat that enable immune evasion are:
307:, the cell surface is covered by a dense coat of ~5 x 10 VSG
537:
494:. Any of these genes can be moved into the active site by
744:
Variable surface glycoproteins are also found in other
582:. Because there is no transcriptional control, the VSG
1457:
Morrison LJ, Marcello L, McCulloch R (December 2009).
1952:"Genome hyperevolution and the success of a parasite"
1950:
Barry JD, Hall JP, Plenderleith L (September 2012).
702:-mediated trypanosome killing can also be observed
486:of new VSG genes. It is estimated up to 10% of the
276:) with other ES-associated genes (ESAGs), of which
171:
161:
156:
140:
132:
124:
112:
107:
102:
84:
79:
67:
59:
51:
39:
34:
29:
1780:Tiengwe C, Muratore KA, Bangs JD (November 2016).
461:and switched on at any given time. The expressed
443:s, which can constitute the major portion of the
439:s allows the (partial) expression of pseudogene
1375:"Antigenic variation in vector-borne pathogens"
807:). The variable surface glycoprotein RoTat 1.2
722:there is a possibility that one or both of the
803:(enzyme-linked immunosorbent assay) and CATT (
376:VSGs are replaced by an equally dense coat of
194:) is a ~60kDa protein which densely packs the
8:
805:card agglutination test for trypanosomiasis
669:VSG is anchored to the cell membrane via a
2327:Variant Surface Glycoproteins, Trypanosoma
2005:
2003:
1956:Annals of the New York Academy of Sciences
531:The variant surface glycoprotein genes of
153:
2329:at the U.S. National Library of Medicine
2300:
2181:
2171:
2094:
2045:
2035:
1983:
1805:
1678:
1668:
1627:
1543:
1533:
1398:
1349:
1300:
1216:
1102:
662:N-terminal domains form a bundle of four
528:have diverged to become strain-specific.
403:. Some of these are full-length, intact
322:or any other parasitic invariant surface
1324:Marcello L, Barry JD (September 2007).
976:
974:
892:
2207:Molecular and Biochemical Parasitology
1569:International Journal for Parasitology
1024:
1014:
671:glycophosphatidylinositol (GPI) anchor
490:genome may be made up of VSG genes or
103:Variant surface glycoprotein MITAT 1.2
99:
26:
1602:Stanne TM, Rudenko G (January 2010).
1191:Triggs VP, Bangs JD (February 2003).
638:VSG genes are hugely variable at the
618:folding cycle (calnexin is absent in
7:
824:, which bears little carbohydrate.
785:, a parasite that causes a form of
2254:10.1111/j.1550-7408.1984.tb02966.x
2087:10.1002/j.1460-2075.1982.tb01328.x
1929:10.1111/j.1574-6968.1997.tb10486.x
983:Advances in Parasitology Volume 49
481:in that site), or by changing the
345:β the VSG coat undergoes frequent
25:
2160:Kinetoplastid Biology and Disease
1167:FAO Corporate document depository
1976:10.1111/j.1749-6632.2012.06654.x
1704:Journal of Cellular Biochemistry
1478:10.1111/j.1462-5822.2009.01383.x
1373:Barbour AG, Restrepo BI (2000).
882:List of MeSH codes (D12.776.543)
877:List of MeSH codes (D12.776.395)
515:expression site associated genes
2281:Molecular Biology and Evolution
1077:Ross R, Thomson D (June 1910).
985:. Vol. 49. pp. 1β70.
789:in animals, has been cloned in
272:(recruited to a ribosomal-type
1281:Molecular and Cellular Biology
435:gene. The formation of mosaic
18:Invariant Surface Glycoprotein
1:
1843:10.1016/S0022-2836(05)80066-X
1581:10.1016/S0020-7519(01)00143-6
991:10.1016/S0065-308X(01)49037-3
862:Coat protein (disambiguation)
594:(on asn-x-ser/thr sites) and
367:glycosyl-phosphatidylinositol
290:human African trypanosomiasis
30:Variable surface glycoprotein
2219:10.1016/0166-6851(96)02687-4
2133:10.1016/j.vetpar.2012.01.012
1831:Journal of Molecular Biology
1535:10.1371/journal.pone.0003527
1379:Emerging Infectious Diseases
1056:10.1016/0169-4758(94)90393-X
957:10.1016/0378-1119(84)90008-8
188:Variant surface glycoprotein
2275:Jackson AP (January 2010).
2242:The Journal of Protozoology
795:. The expressed protein is
626:GPI anchor by GPI-specific
502:machinery and a process of
2378:
1917:FEMS Microbiology Letters
1209:10.1128/ec.2.1.76-83.2003
914:10.1017/s003118200004717x
759:, a parasite causing the
152:
2331:Medical Subject Headings
1436:10.1016/j.pt.2005.08.016
872:List of MeSH codes (D23)
524:The gene repertoires in
504:homologous recombination
351:specific immune response
282:homologous recombination
2121:Veterinary Parasitology
2037:10.1073/pnas.80.14.4306
1670:10.1186/1471-2164-8-234
1242:Journal of Cell Science
1095:10.1136/bmj.1.2582.1544
1083:British Medical Journal
610:VSG then undergoes the
369:(GPI) anchors (one per
205:belonging to the genus
2352:Kinetoplastid proteins
1424:Trends in Parasitology
1391:10.3201/eid0605.000502
1128:Essays in Biochemistry
830:Trypanosoma congolense
766:Trypanosoma equiperdum
756:Trypanosoma equiperdum
718:. However, with each
682:
544:
241:
2293:10.1093/molbev/msp214
2173:10.1186/1475-9292-3-3
1786:Cellular Microbiology
1759:10.1093/glycob/cwf079
1716:10.1002/jcb.240240309
1466:Cellular Microbiology
740:In other trypanosomes
679:
580:polypyrimidine tracts
548:Secretory trafficking
541:
396:genes present in the
235:
1293:10.1128/mcb.9.9.4018
598:at the Ο site by a
413:frameshift mutations
278:transferrin receptor
2362:Parasitic excavates
2028:1983PNAS...80.4306R
1968:2012NYASA1267...11B
1878:1993Natur.362..603B
1620:10.1128/EC.00281-09
1526:2008PLoSO...3.3527H
1508:Berriman M (2008).
1248:(Pt 23): 5499β511.
1161:Grab DJ, Verjee Y.
710:complement-mediated
686:Antigenic variation
343:antigenic variation
223:antigenic variation
1342:10.1101/gr.6421207
1140:10.1042/bse0510047
1044:Parasitology Today
782:Trypanosoma evansi
683:
653:of around 300β350
620:Trypanosoma brucei
545:
457:genes can be kept
305:Trypanosoma brucei
298:Trypanosoma brucei
242:
238:Trypanosoma brucei
214:Trypanosoma brucei
118:Trypanosoma brucei
45:Trypanosoma brucei
2337:www.icp.ucl.ac.be
1798:10.1111/cmi.12605
1792:(11): 1673β1688.
1254:10.1242/jcs.02667
1000:978-0-12-031749-3
821:Trypanosoma vivax
761:covering sickness
511:complement system
185:
184:
181:
180:
98:
97:
92:5: 1.41 - 1.41 Mb
16:(Redirected from
2369:
2315:
2314:
2304:
2272:
2266:
2265:
2237:
2231:
2230:
2202:
2196:
2195:
2185:
2175:
2151:
2145:
2144:
2115:
2109:
2108:
2098:
2075:The EMBO Journal
2066:
2060:
2059:
2049:
2039:
2007:
1998:
1997:
1987:
1947:
1941:
1940:
1912:
1906:
1905:
1886:10.1038/362603a0
1861:
1855:
1854:
1826:
1820:
1819:
1809:
1777:
1771:
1770:
1742:
1736:
1735:
1699:
1693:
1692:
1682:
1672:
1648:
1642:
1641:
1631:
1599:
1593:
1592:
1564:
1558:
1557:
1547:
1537:
1504:
1498:
1497:
1463:
1454:
1448:
1447:
1419:
1413:
1412:
1402:
1370:
1364:
1363:
1353:
1321:
1315:
1314:
1304:
1272:
1266:
1265:
1237:
1231:
1230:
1220:
1188:
1182:
1181:
1179:
1178:
1158:
1152:
1151:
1123:
1117:
1116:
1106:
1089:(2582): 1544β5.
1074:
1068:
1067:
1039:
1033:
1032:
1026:
1022:
1020:
1012:
978:
969:
968:
940:
934:
933:
897:
792:Escherichia coli
779:A VSG gene from
572:poly-adenylation
411:(typically with
270:RNA polymerase I
154:
120:
100:
47:
27:
21:
2377:
2376:
2372:
2371:
2370:
2368:
2367:
2366:
2342:
2341:
2323:
2318:
2274:
2273:
2269:
2239:
2238:
2234:
2204:
2203:
2199:
2153:
2152:
2148:
2117:
2116:
2112:
2068:
2067:
2063:
2022:(14): 4306β10.
2009:
2008:
2001:
1949:
1948:
1944:
1914:
1913:
1909:
1872:(6421): 603β9.
1863:
1862:
1858:
1828:
1827:
1823:
1779:
1778:
1774:
1744:
1743:
1739:
1701:
1700:
1696:
1650:
1649:
1645:
1608:Eukaryotic Cell
1601:
1600:
1596:
1575:(5β6): 523β31.
1566:
1565:
1561:
1506:
1505:
1501:
1472:(12): 1724β34.
1461:
1456:
1455:
1451:
1421:
1420:
1416:
1372:
1371:
1367:
1330:Genome Research
1323:
1322:
1318:
1274:
1273:
1269:
1239:
1238:
1234:
1197:Eukaryotic Cell
1190:
1189:
1185:
1176:
1174:
1160:
1159:
1155:
1125:
1124:
1120:
1076:
1075:
1071:
1041:
1040:
1036:
1023:
1013:
1001:
980:
979:
972:
942:
941:
937:
899:
898:
894:
890:
852:
742:
696:immune response
688:
636:
605:N-glycosylation
565:Golgi apparatus
550:
390:
320:plasma membrane
301:
262:minichromosomes
260:chromosomes or
116:
43:
23:
22:
15:
12:
11:
5:
2375:
2373:
2365:
2364:
2359:
2354:
2344:
2343:
2340:
2339:
2334:
2322:
2321:External links
2319:
2317:
2316:
2267:
2232:
2197:
2146:
2110:
2081:(11): 1393β8.
2061:
1999:
1942:
1907:
1856:
1821:
1772:
1753:(10): 607β12.
1737:
1694:
1643:
1594:
1559:
1499:
1449:
1430:(11): 517β20.
1414:
1365:
1336:(9): 1344β52.
1316:
1287:(9): 4018β21.
1267:
1232:
1183:
1153:
1118:
1069:
1034:
1025:|journal=
999:
970:
935:
908:(3): 393β417.
891:
889:
886:
885:
884:
879:
874:
869:
864:
859:
851:
848:
797:immunoreactive
774:phosphorylated
741:
738:
690:VSG is highly
687:
684:
635:
632:
600:transamination
592:N-glycosylated
576:trans-splicing
549:
546:
389:
386:
361:The VSGs from
359:
358:
354:
339:
300:
294:
248:)) located in
183:
182:
179:
178:
173:
169:
168:
163:
159:
158:
150:
149:
144:
138:
137:
134:
130:
129:
126:
122:
121:
114:
110:
109:
105:
104:
96:
95:
88:
82:
81:
77:
76:
71:
65:
64:
61:
57:
56:
53:
49:
48:
41:
37:
36:
32:
31:
24:
14:
13:
10:
9:
6:
4:
3:
2:
2374:
2363:
2360:
2358:
2357:Glycoproteins
2355:
2353:
2350:
2349:
2347:
2338:
2335:
2332:
2328:
2325:
2324:
2320:
2312:
2308:
2303:
2298:
2294:
2290:
2286:
2282:
2278:
2271:
2268:
2263:
2259:
2255:
2251:
2247:
2243:
2236:
2233:
2228:
2224:
2220:
2216:
2212:
2208:
2201:
2198:
2193:
2189:
2184:
2179:
2174:
2169:
2165:
2161:
2157:
2150:
2147:
2142:
2138:
2134:
2130:
2126:
2122:
2114:
2111:
2106:
2102:
2097:
2092:
2088:
2084:
2080:
2076:
2072:
2065:
2062:
2057:
2053:
2048:
2043:
2038:
2033:
2029:
2025:
2021:
2017:
2013:
2006:
2004:
2000:
1995:
1991:
1986:
1981:
1977:
1973:
1969:
1965:
1961:
1957:
1953:
1946:
1943:
1938:
1934:
1930:
1926:
1923:(1): 227β31.
1922:
1918:
1911:
1908:
1903:
1899:
1895:
1891:
1887:
1883:
1879:
1875:
1871:
1867:
1860:
1857:
1852:
1848:
1844:
1840:
1837:(1): 141β60.
1836:
1832:
1825:
1822:
1817:
1813:
1808:
1803:
1799:
1795:
1791:
1787:
1783:
1776:
1773:
1768:
1764:
1760:
1756:
1752:
1748:
1741:
1738:
1733:
1729:
1725:
1721:
1717:
1713:
1710:(3): 287β95.
1709:
1705:
1698:
1695:
1690:
1686:
1681:
1676:
1671:
1666:
1662:
1658:
1654:
1647:
1644:
1639:
1635:
1630:
1625:
1621:
1617:
1614:(1): 136β47.
1613:
1609:
1605:
1598:
1595:
1590:
1586:
1582:
1578:
1574:
1570:
1563:
1560:
1555:
1551:
1546:
1541:
1536:
1531:
1527:
1523:
1520:(10): e3527.
1519:
1515:
1511:
1503:
1500:
1495:
1491:
1487:
1483:
1479:
1475:
1471:
1467:
1460:
1453:
1450:
1445:
1441:
1437:
1433:
1429:
1425:
1418:
1415:
1410:
1406:
1401:
1396:
1392:
1388:
1385:(5): 449β57.
1384:
1380:
1376:
1369:
1366:
1361:
1357:
1352:
1347:
1343:
1339:
1335:
1331:
1327:
1320:
1317:
1312:
1308:
1303:
1298:
1294:
1290:
1286:
1282:
1278:
1271:
1268:
1263:
1259:
1255:
1251:
1247:
1243:
1236:
1233:
1228:
1224:
1219:
1214:
1210:
1206:
1202:
1198:
1194:
1187:
1184:
1173:on 2018-08-31
1172:
1168:
1164:
1157:
1154:
1149:
1145:
1141:
1137:
1133:
1129:
1122:
1119:
1114:
1110:
1105:
1100:
1096:
1092:
1088:
1084:
1080:
1073:
1070:
1065:
1061:
1057:
1053:
1049:
1045:
1038:
1035:
1030:
1018:
1010:
1006:
1002:
996:
992:
988:
984:
977:
975:
971:
966:
962:
958:
954:
951:(3): 329β36.
950:
946:
939:
936:
931:
927:
923:
919:
915:
911:
907:
903:
896:
893:
887:
883:
880:
878:
875:
873:
870:
868:
865:
863:
860:
857:
854:
853:
849:
847:
844:
840:
836:
832:
831:
825:
823:
822:
816:
814:
810:
806:
802:
798:
794:
793:
788:
784:
783:
777:
775:
771:
770:T. equiperdum
767:
762:
758:
757:
751:
749:
748:
739:
737:
734:
730:
725:
721:
720:cell division
717:
714:
711:
707:
706:
701:
697:
693:
685:
678:
674:
672:
667:
665:
664:alpha helices
660:
656:
652:
649:
645:
641:
633:
631:
629:
623:
621:
617:
613:
608:
606:
601:
597:
593:
589:
585:
581:
577:
573:
568:
566:
562:
558:
554:
547:
540:
536:
534:
529:
527:
522:
520:
516:
512:
507:
505:
501:
497:
496:recombination
493:
489:
484:
480:
475:
472:
469:found at the
468:
464:
460:
456:
452:
451:development.
450:
446:
442:
438:
434:
430:
426:
422:
418:
414:
410:
407:; others are
406:
402:
399:
395:
387:
385:
383:
379:
374:
372:
368:
364:
355:
352:
348:
344:
340:
337:
333:
329:
325:
321:
317:
316:
315:
312:
310:
306:
299:
295:
293:
291:
286:
283:
279:
275:
271:
267:
263:
259:
255:
251:
247:
239:
234:
230:
228:
224:
220:
216:
215:
210:
209:
204:
201:
197:
193:
189:
177:
174:
170:
167:
164:
160:
155:
151:
148:
145:
143:
139:
135:
131:
127:
123:
119:
115:
111:
106:
101:
94:
93:
89:
87:
83:
78:
75:
72:
70:
66:
63:Tb05.26C7.380
62:
58:
54:
50:
46:
42:
38:
33:
28:
19:
2287:(1): 33β45.
2284:
2280:
2270:
2248:(2): 300β6.
2245:
2241:
2235:
2210:
2206:
2200:
2163:
2159:
2149:
2127:(1β2): 1β8.
2124:
2120:
2113:
2078:
2074:
2064:
2019:
2015:
1959:
1955:
1945:
1920:
1916:
1910:
1869:
1865:
1859:
1834:
1830:
1824:
1789:
1785:
1775:
1750:
1747:Glycobiology
1746:
1740:
1707:
1703:
1697:
1660:
1657:BMC Genomics
1656:
1646:
1611:
1607:
1597:
1572:
1568:
1562:
1517:
1513:
1502:
1469:
1465:
1452:
1427:
1423:
1417:
1382:
1378:
1368:
1333:
1329:
1319:
1284:
1280:
1270:
1245:
1241:
1235:
1203:(1): 76β83.
1200:
1196:
1186:
1175:. Retrieved
1171:the original
1166:
1156:
1131:
1127:
1121:
1086:
1082:
1072:
1047:
1043:
1037:
982:
948:
944:
938:
905:
902:Parasitology
901:
895:
834:
828:
826:
819:
817:
815:infections.
812:
790:
780:
778:
769:
765:
754:
752:
745:
743:
732:
728:
703:
689:
668:
637:
624:
619:
612:calreticulin
609:
596:GPI anchored
578:directed by
569:
552:
551:
532:
530:
525:
523:
514:
508:
487:
482:
478:
476:
462:
454:
453:
444:
440:
436:
432:
428:
427:or 'mosaic'
420:
415:, premature
397:
393:
391:
375:
362:
360:
332:transporters
328:ion channels
313:
304:
302:
297:
287:
254:subtelomeric
243:
237:
219:George Cross
212:
206:
196:cell surface
191:
187:
186:
133:Alt. symbols
90:
60:Alt. symbols
55:Tb927.5.4730
2213:(1): 1β11.
1962:(1): 11β7.
1050:(2): 53β8.
839:glucosamine
747:Trypanosoma
692:immunogenic
655:amino acids
553:Trypanosoma
519:nucleosomes
492:pseudogenes
417:stop codons
409:pseudogenes
266:polycistron
256:arrays (on
246:pseudogenes
229:activity.
227:biochemical
217:in 1975 by
208:Trypanosoma
166:Swiss-model
108:Identifiers
35:Identifiers
2346:Categories
1177:2013-07-28
888:References
867:Glycocalyx
659:C terminal
648:N terminal
644:structural
500:DNA repair
388:Expression
382:tsetse fly
378:procyclins
347:stochastic
162:Structures
157:Search for
86:Chromosome
80:Other data
1134:: 47β62.
1027:ignored (
1017:cite book
813:T. evansi
772:are also
750:species.
733:T. brucei
694:, and an
634:Structure
588:polysomes
533:T. brucei
526:T. brucei
471:telomeres
398:T. brucei
363:T. brucei
341:Periodic
336:receptors
326:(such as
250:telomeric
203:parasites
200:protozoan
2311:19748930
2192:15377385
2166:(1): 3.
2141:22277627
1994:22954210
1816:27110662
1767:12244073
1689:17629915
1638:19915073
1589:11334937
1554:18953401
1514:PLOS ONE
1494:26552797
1486:19751359
1444:16126458
1409:10998374
1360:17652423
1262:16291721
1227:12582124
1148:22023441
1113:20765166
1064:15275499
1009:11461029
930:20749130
850:See also
835:in vitro
705:in vitro
700:Antibody
640:sequence
616:calnexin
561:lysosome
488:T.brucei
425:chimeric
324:epitopes
274:promoter
258:megabase
176:InterPro
113:Organism
40:Organism
2302:2794310
2262:6470988
2227:8943146
2105:6821334
2056:6308614
2024:Bibcode
1985:3467770
1964:Bibcode
1937:9252591
1902:4370099
1894:8464512
1874:Bibcode
1851:2231728
1807:5575760
1724:6736139
1680:1934917
1663:: 234.
1629:2805301
1545:2567434
1522:Bibcode
1400:2627965
1351:1950903
1311:2779574
1104:2331906
965:6530143
856:Amastin
843:mannose
729:in vivo
724:progeny
449:vaccine
371:monomer
172:Domains
142:UniProt
136:VSG 221
74:3657576
2333:(MeSH)
2309:
2299:
2260:
2225:
2190:
2183:521498
2180:
2139:
2103:
2096:553222
2093:
2054:
2047:384026
2044:
1992:
1982:
1935:
1900:
1892:
1866:Nature
1849:
1814:
1804:
1765:
1730:
1722:
1687:
1677:
1636:
1626:
1587:
1552:
1542:
1492:
1484:
1442:
1407:
1397:
1358:
1348:
1309:
1302:362464
1299:
1260:
1225:
1218:141176
1215:
1146:
1111:
1101:
1062:
1007:
997:
963:
928:
920:
731:. As
651:domain
563:, and
459:silent
401:genome
309:dimers
147:P26332
125:Symbol
69:Entrez
52:Symbol
1898:S2CID
1732:73535
1728:S2CID
1490:S2CID
1462:(PDF)
926:S2CID
801:ELISA
787:surra
716:assay
713:lysis
708:by a
584:3'UTR
405:genes
2307:PMID
2258:PMID
2223:PMID
2188:PMID
2137:PMID
2101:PMID
2052:PMID
1990:PMID
1960:1267
1933:PMID
1890:PMID
1847:PMID
1812:PMID
1763:PMID
1720:PMID
1685:PMID
1634:PMID
1585:PMID
1550:PMID
1482:PMID
1440:PMID
1405:PMID
1356:PMID
1307:PMID
1258:PMID
1223:PMID
1144:PMID
1109:PMID
1060:PMID
1029:help
1005:PMID
995:ISBN
961:PMID
945:Gene
918:PMID
841:and
574:and
467:loci
252:and
236:The
2297:PMC
2289:doi
2250:doi
2215:doi
2178:PMC
2168:doi
2129:doi
2125:187
2091:PMC
2083:doi
2042:PMC
2032:doi
1980:PMC
1972:doi
1925:doi
1921:153
1882:doi
1870:362
1839:doi
1835:216
1802:PMC
1794:doi
1755:doi
1712:doi
1675:PMC
1665:doi
1624:PMC
1616:doi
1577:doi
1540:PMC
1530:doi
1474:doi
1432:doi
1395:PMC
1387:doi
1346:PMC
1338:doi
1297:PMC
1289:doi
1250:doi
1246:118
1213:PMC
1205:doi
1136:doi
1099:PMC
1091:doi
1052:doi
987:doi
953:doi
922:645
910:doi
827:In
809:PCR
753:In
628:PLC
483:VSG
479:VSG
463:VSG
455:VSG
445:VSG
441:VSG
437:VSG
433:VSG
429:VSG
421:VSG
394:VSG
303:In
296:In
268:by
198:of
192:VSG
128:N/A
2348::
2305:.
2295:.
2285:27
2283:.
2279:.
2256:.
2246:31
2244:.
2221:.
2211:82
2209:.
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