528:
527:
274:
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.
281:. 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.
532:
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.
662: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.
214:. 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
725:
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).
222:
666:
611:), 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.
614:
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
531:
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
752:
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
474:
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
273:
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
669:
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
724:
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
462:
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
345:
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
1496:
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,
650:
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
834:
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.
635:(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
591:
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
502:. 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
2107:
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".
715:
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.
229:
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.
1818:
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".
346:
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.
1315:"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"
1734:
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".
757:
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
327:
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.
2194:
Gardiner PR, Nene V, Barry MM, Thatthi R, Burleigh B, Clarke MW (November 1996). "Characterization of a small variable surface glycoprotein from
Trypanosoma vivax".
498:
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
1853:
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".
362:), which directs its forward-trafficking from the ER to the flagellar pocket for incorporation into the membrane, as predicted by the GPI valence hypothesis.
80:
889:
Cross GA (1975). "Identification, purification and properties of clone-specific glycoprotein antigens constituting the surface coat of
Trypanosoma brucei".
436:
archive, and can contribute directly to antigenic variation, vastly increasing the trypanosome's capacity for immune evasion and posing a major problem for
1556:
Vanhamme L, Lecordier L, Pays E (May 2001). "Control and function of the bloodstream variant surface glycoprotein expression sites in
Trypanosoma brucei".
307:
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
932:
Buck GA, Jacquemot C, Baltz T, Eisen H (December 1984). "Re-expression of an inactivated variable surface glycoprotein gene in
Trypanosoma equiperdum".
579:, 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
269:(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
1691:
Young JR, Turner MJ, Williams RO (1984). "The role of duplication in the expression of a variable surface glycoprotein gene of
Trypanosoma brucei".
342:
raised against the previous coat. This antigenic variation creates cyclical waves of parasitemia characteristic of Human African Trypanosomiasis.
1229:
Schwartz KJ, Peck RF, Tazeh NN, Bangs JD (December 2005). "GPI valence and the fate of secretory membrane proteins in African trypanosomes".
1031:
Overath P, Chaudhri M, Steverding D, Ziegelbauer K (February 1994). "Invariant surface proteins in bloodstream forms of Trypanosoma brucei".
987:
2229:
Reinwald E, Heidrich C, Risse HJ (May 1984). "In vitro studies on the biosynthesis of the surface glycoprotein of Trypanosoma congolense".
788:
with all the sera combinations. The animals immunized with whole cell lysate or recombinant protein show similar antibody reactions in
1904:
Turner CM (August 1997). "The rate of antigenic variation in fly-transmitted and syringe-passaged infections of Trypanosoma brucei".
506:(ESAGs). There is a collection of an estimated 20-30 sites, each being active at a time. Active VSG expression sites are depleted of
1151:
655:
directed by hydrophobic interactions, around which hang smaller structural features (five smaller helices and three beta-sheets).
870:
865:
524:
have been classified into two groups depending upon whether or not duplication of the genes is observed when they are expressed.
62:
2340:
572:
2145:"Variable Surface Glycoprotein RoTat 1.2 PCR as a specific diagnostic tool for the detection of Trypanosoma evansi infections"
970:
Barry JD, McCulloch R (2001). "Antigenic variation in trypanosomes: enhanced phenotypic variation in a eukaryotic parasite".
1152:"Localization of a Variable Surface Glycoprotein Phosphatidylinositol-Specific Phospholipase-C in Trypanosoma brucei brucei"
596:
sites per VSG may vary (usually 1-3 N-glycans). VSG MITat.1.5 is glycosylated at all three potential N-glycosylation sites.
408:, or fragmentation). Expression of an antigenically different VSG can occur by simply switching to a different full-length
850:
355:
278:
2350:
2315:
670:
variable primary sequence allows for VSG to be antigenically distinct from one another, the crux to antigenic variation.
643:
584:
600:
373:
midgut. There is a very fast inhibition of VSG gene transcription which occurs as soon as the temperature is lowered.
575:
is important for its RNA stability (most importantly, the 8mer and 14mer). VSG is then transcribed on membrane-bound
466:
The expressed VSG can be switched either by activating a different expression site (and thus changing to express the
797:
659:
2319:
860:
492:
270:
233:
The parasite has a large cellular repertoire of antigenically distinct VSGs (~1500/2000 complete and partial (
106:
33:
1642:"Variant Surface Glycoprotein gene repertoires in Trypanosoma brucei have diverged to become strain-specific"
753:
this prevents the body from mounting a large enough immune response to eradicate the disease. In this sense,
793:
487:
for expression. Again, the exact mechanisms that control this are unclear, but the process seems to rely on
1266:"Trypanosoma brucei: posttranscriptional control of the variable surface glycoprotein gene expression site"
2345:
818:
744:
580:
545:
484:
2012:
1952:
1862:
1510:
568:
401:
320:
297:
277:
The antigenic variation causes cyclical waves of parasitemia, which is one of the characteristics of
266:
254:
1182:"Glycosylphosphatidylinositol-dependent protein trafficking in bloodstream stage Trypanosoma brucei"
331:
262:
211:
210:. VSG allows the trypanosomatid parasites to evade the mammalian host's immune system by extensive
1886:
1716:
1478:
1005:
914:
770:
207:
202:
1448:"Antigenic variation in the African trypanosome: molecular mechanisms and phenotypic complexity"
1115:
Rudenko G (2011-10-24). "African trypanosomes: the genome and adaptations for immune evasion".
2295:
2246:
2211:
2176:
2125:
2089:
2040:
1978:
1921:
1878:
1835:
1800:
1751:
1708:
1673:
1622:
1573:
1538:
1470:
1428:
1393:
1344:
1295:
1246:
1211:
1132:
1097:
1048:
993:
983:
949:
906:
809:
749:
698:
684:
632:
499:
339:
844:
2285:
2277:
2238:
2203:
2166:
2156:
2117:
2079:
2071:
2030:
2020:
1968:
1960:
1913:
1870:
1827:
1790:
1782:
1743:
1700:
1663:
1653:
1640:
Hutchinson OC, Picozzi K, Jones NG, Mott H, Sharma R, Welburn SC, Carrington M (July 2007).
1612:
1604:
1565:
1528:
1518:
1462:
1420:
1383:
1375:
1334:
1326:
1285:
1277:
1238:
1201:
1193:
1124:
1087:
1079:
1068:"A Case of Sleeping Sickness showing Regular Periodical Increase of the Parasites Disclosed"
1040:
975:
941:
898:
780:
455:
258:
687:
raised against a specific VSG coat will rapidly kill trypanosomes expressing this variant.
338:
genetic modificationβ'switching'βallowing variants expressing a new VSG coat to escape the
1017:
616:
593:
560:
553:
154:
2016:
1956:
1866:
1514:
2290:
2265:
2242:
2075:
1973:
1940:
1917:
1795:
1770:
1668:
1641:
1617:
1592:
1533:
1498:
1411:
Pays E (November 2005). "Regulation of antigen gene expression in Trypanosoma brucei".
1388:
1363:
1339:
1314:
1159:
1092:
1067:
785:
762:
639:
628:
588:
564:
447:
250:
200:. This genus is notable for their cell surface proteins. They were first isolated from
2171:
2144:
2084:
2059:
2035:
2000:
1999:
Raibaud A, Gaillard C, Longacre S, Hibner U, Buck G, Bernardi G, Eisen H (July 1983).
1831:
1569:
1290:
1265:
1206:
1181:
979:
2334:
2325:
2207:
2143:
Claes F, Radwanska M, Urakawa T, Majiwa PA, Goddeeris B, BΓΌscher P (September 2004).
1964:
1466:
1044:
945:
826:
analyses of the incorporated sugars after hydrolysis of the glycoprotein showed that
708:
559:
VSG is first transcribed as a polycistron and then undergoes trypanosomatid-specific
413:
324:
308:
184:
1482:
918:
2058:
Baltz T, Giroud C, Baltz D, Duvillier G, Degand P, Demaille J, Pautrizel R (1982).
1890:
316:
242:
215:
463:
involved in this process, but the exact nature of the silencing is still unclear.
221:
2121:
2060:"The variable surface glycoproteins of Trypanosoma equiperdum are phosphorylated"
1720:
1523:
2001:"Genomic environment of variant surface antigen genes of Trypanosoma equiperdum"
827:
735:
680:
652:
480:
412:
gene by Expression Site switching (switching which ES is active). In addition,
405:
196:
164:
2005:
Proceedings of the National Academy of Sciences of the United States of America
1593:"Active VSG expression sites in Trypanosoma brucei are depleted of nucleosomes"
454:
is always located in an Expression Site (ES), which are specialised expression
1197:
902:
855:
647:
636:
507:
488:
397:
370:
335:
246:
234:
191:
130:
74:
1424:
2281:
2266:"The evolution of amastin surface glycoproteins in trypanosomatid parasites"
2025:
1747:
1658:
1083:
847:, another surface (trans-membrane) glycoprotein in trypanosomatid parasites
712:
459:
366:
2299:
2180:
2129:
1982:
1804:
1755:
1677:
1626:
1577:
1542:
1474:
1447:
1432:
1397:
1379:
1348:
1250:
1215:
1136:
1101:
1052:
997:
807:
The smallest VSG protein (40 kDa in size) to date (1996) has been found in
2250:
2215:
2161:
2093:
2044:
1925:
1882:
1839:
1712:
1704:
1299:
1158:. Food and Agricultural Organization of the United Nations. Archived from
953:
665:
544:
have a simple, polarized membrane transport system consisting of a single
1281:
693:
688:
604:
576:
549:
312:
238:
188:
135:
1608:
253:). VSGs are expressed from a bloodstream expression site (BES, ES) in a
1499:"Telomeric expression sites are highly conserved in Trypanosoma brucei"
1330:
1128:
831:
437:
420:
genes can be generated by combining segments from more than one silent
381:
The source of VSG variability during infection is a large 'archive' of
359:
1786:
1771:"Surface proteins, ERAD and antigenic variation in Trypanosoma brucei"
1242:
910:
1874:
631:(primary) level, but variants are thought to have strongly conserved
389:
354:
are attached to the plasma membrane via a covalent attachment to two
57:
1264:
Pays E, Coquelet H, Pays A, Tebabi P, Steinert M (September 1989).
646:
with low sequence homology (13β30% identity), and a more conserved
300:, ~90% of all cell surface protein and ~10% of total cell protein.
789:
775:
704:
701:
664:
393:
220:
369:
when the parasite differentiates into the procyclic form in the
800:
can be used as a specific diagnostic tool for the detection of
303:
The properties of the VSG coat that enable immune evasion are:
296:, the cell surface is covered by a dense coat of ~5 x 10 VSG
526:
483:. Any of these genes can be moved into the active site by
733:
Variable surface glycoproteins are also found in other
571:. Because there is no transcriptional control, the VSG
1446:
Morrison LJ, Marcello L, McCulloch R (December 2009).
1941:"Genome hyperevolution and the success of a parasite"
1939:
Barry JD, Hall JP, Plenderleith L (September 2012).
691:-mediated trypanosome killing can also be observed
475:of new VSG genes. It is estimated up to 10% of the
265:) with other ES-associated genes (ESAGs), of which
160:
150:
145:
129:
121:
113:
101:
96:
91:
73:
68:
56:
48:
40:
28:
23:
18:
1769:Tiengwe C, Muratore KA, Bangs JD (November 2016).
450:and switched on at any given time. The expressed
432:s, which can constitute the major portion of the
428:s allows the (partial) expression of pseudogene
1364:"Antigenic variation in vector-borne pathogens"
796:). The variable surface glycoprotein RoTat 1.2
711:there is a possibility that one or both of the
792:(enzyme-linked immunosorbent assay) and CATT (
365:VSGs are replaced by an equally dense coat of
183:) is a ~60kDa protein which densely packs the
8:
794:card agglutination test for trypanosomiasis
658:VSG is anchored to the cell membrane via a
2316:Variant Surface Glycoproteins, Trypanosoma
1994:
1992:
1945:Annals of the New York Academy of Sciences
520:The variant surface glycoprotein genes of
142:
2318:at the U.S. National Library of Medicine
2289:
2170:
2160:
2083:
2034:
2024:
1972:
1794:
1667:
1657:
1616:
1532:
1522:
1387:
1338:
1289:
1205:
1091:
651:N-terminal domains form a bundle of four
517:have diverged to become strain-specific.
392:. Some of these are full-length, intact
311:or any other parasitic invariant surface
1313:Marcello L, Barry JD (September 2007).
965:
963:
881:
2196:Molecular and Biochemical Parasitology
1558:International Journal for Parasitology
1013:
1003:
660:glycophosphatidylinositol (GPI) anchor
479:genome may be made up of VSG genes or
92:Variant surface glycoprotein MITAT 1.2
88:
15:
1591:Stanne TM, Rudenko G (January 2010).
1180:Triggs VP, Bangs JD (February 2003).
627:VSG genes are hugely variable at the
607:folding cycle (calnexin is absent in
7:
813:, which bears little carbohydrate.
774:, a parasite that causes a form of
2243:10.1111/j.1550-7408.1984.tb02966.x
2076:10.1002/j.1460-2075.1982.tb01328.x
1918:10.1111/j.1574-6968.1997.tb10486.x
972:Advances in Parasitology Volume 49
470:in that site), or by changing the
334:β the VSG coat undergoes frequent
14:
2149:Kinetoplastid Biology and Disease
1156:FAO Corporate document depository
1965:10.1111/j.1749-6632.2012.06654.x
1693:Journal of Cellular Biochemistry
1467:10.1111/j.1462-5822.2009.01383.x
1362:Barbour AG, Restrepo BI (2000).
871:List of MeSH codes (D12.776.543)
866:List of MeSH codes (D12.776.395)
504:expression site associated genes
2270:Molecular Biology and Evolution
1066:Ross R, Thomson D (June 1910).
974:. Vol. 49. pp. 1β70.
778:in animals, has been cloned in
261:(recruited to a ribosomal-type
1270:Molecular and Cellular Biology
424:gene. The formation of mosaic
1:
1832:10.1016/S0022-2836(05)80066-X
1570:10.1016/S0020-7519(01)00143-6
980:10.1016/S0065-308X(01)49037-3
851:Coat protein (disambiguation)
583:(on asn-x-ser/thr sites) and
356:glycosyl-phosphatidylinositol
279:human African trypanosomiasis
19:Variable surface glycoprotein
2208:10.1016/0166-6851(96)02687-4
2122:10.1016/j.vetpar.2012.01.012
1820:Journal of Molecular Biology
1524:10.1371/journal.pone.0003527
1368:Emerging Infectious Diseases
1045:10.1016/0169-4758(94)90393-X
946:10.1016/0378-1119(84)90008-8
177:Variant surface glycoprotein
2264:Jackson AP (January 2010).
2231:The Journal of Protozoology
784:. The expressed protein is
615:GPI anchor by GPI-specific
491:machinery and a process of
2367:
1906:FEMS Microbiology Letters
1198:10.1128/ec.2.1.76-83.2003
903:10.1017/s003118200004717x
748:, a parasite causing the
141:
2320:Medical Subject Headings
1425:10.1016/j.pt.2005.08.016
861:List of MeSH codes (D23)
513:The gene repertoires in
493:homologous recombination
340:specific immune response
271:homologous recombination
2110:Veterinary Parasitology
2026:10.1073/pnas.80.14.4306
1659:10.1186/1471-2164-8-234
1231:Journal of Cell Science
1084:10.1136/bmj.1.2582.1544
1072:British Medical Journal
599:VSG then undergoes the
358:(GPI) anchors (one per
194:belonging to the genus
2341:Kinetoplastid proteins
1413:Trends in Parasitology
1380:10.3201/eid0605.000502
1117:Essays in Biochemistry
819:Trypanosoma congolense
755:Trypanosoma equiperdum
745:Trypanosoma equiperdum
707:. However, with each
671:
533:
230:
2282:10.1093/molbev/msp214
2162:10.1186/1475-9292-3-3
1775:Cellular Microbiology
1748:10.1093/glycob/cwf079
1705:10.1002/jcb.240240309
1455:Cellular Microbiology
729:In other trypanosomes
668:
569:polypyrimidine tracts
537:Secretory trafficking
530:
385:genes present in the
224:
1282:10.1128/mcb.9.9.4018
587:at the Ο site by a
402:frameshift mutations
267:transferrin receptor
2351:Parasitic excavates
2017:1983PNAS...80.4306R
1957:2012NYASA1267...11B
1867:1993Natur.362..603B
1609:10.1128/EC.00281-09
1515:2008PLoSO...3.3527H
1497:Berriman M (2008).
1237:(Pt 23): 5499β511.
1150:Grab DJ, Verjee Y.
699:complement-mediated
675:Antigenic variation
332:antigenic variation
212:antigenic variation
1331:10.1101/gr.6421207
1129:10.1042/bse0510047
1033:Parasitology Today
771:Trypanosoma evansi
672:
642:of around 300β350
609:Trypanosoma brucei
534:
446:genes can be kept
294:Trypanosoma brucei
287:Trypanosoma brucei
231:
227:Trypanosoma brucei
203:Trypanosoma brucei
107:Trypanosoma brucei
34:Trypanosoma brucei
2326:www.icp.ucl.ac.be
1787:10.1111/cmi.12605
1781:(11): 1673β1688.
1243:10.1242/jcs.02667
989:978-0-12-031749-3
810:Trypanosoma vivax
750:covering sickness
500:complement system
174:
173:
170:
169:
87:
86:
81:5: 1.41 - 1.41 Mb
2358:
2304:
2303:
2293:
2261:
2255:
2254:
2226:
2220:
2219:
2191:
2185:
2184:
2174:
2164:
2140:
2134:
2133:
2104:
2098:
2097:
2087:
2064:The EMBO Journal
2055:
2049:
2048:
2038:
2028:
1996:
1987:
1986:
1976:
1936:
1930:
1929:
1901:
1895:
1894:
1875:10.1038/362603a0
1850:
1844:
1843:
1815:
1809:
1808:
1798:
1766:
1760:
1759:
1731:
1725:
1724:
1688:
1682:
1681:
1671:
1661:
1637:
1631:
1630:
1620:
1588:
1582:
1581:
1553:
1547:
1546:
1536:
1526:
1493:
1487:
1486:
1452:
1443:
1437:
1436:
1408:
1402:
1401:
1391:
1359:
1353:
1352:
1342:
1310:
1304:
1303:
1293:
1261:
1255:
1254:
1226:
1220:
1219:
1209:
1177:
1171:
1170:
1168:
1167:
1147:
1141:
1140:
1112:
1106:
1105:
1095:
1078:(2582): 1544β5.
1063:
1057:
1056:
1028:
1022:
1021:
1015:
1011:
1009:
1001:
967:
958:
957:
929:
923:
922:
886:
781:Escherichia coli
768:A VSG gene from
561:poly-adenylation
400:(typically with
259:RNA polymerase I
143:
109:
89:
36:
16:
2366:
2365:
2361:
2360:
2359:
2357:
2356:
2355:
2331:
2330:
2312:
2307:
2263:
2262:
2258:
2228:
2227:
2223:
2193:
2192:
2188:
2142:
2141:
2137:
2106:
2105:
2101:
2057:
2056:
2052:
2011:(14): 4306β10.
1998:
1997:
1990:
1938:
1937:
1933:
1903:
1902:
1898:
1861:(6421): 603β9.
1852:
1851:
1847:
1817:
1816:
1812:
1768:
1767:
1763:
1733:
1732:
1728:
1690:
1689:
1685:
1639:
1638:
1634:
1597:Eukaryotic Cell
1590:
1589:
1585:
1564:(5β6): 523β31.
1555:
1554:
1550:
1495:
1494:
1490:
1461:(12): 1724β34.
1450:
1445:
1444:
1440:
1410:
1409:
1405:
1361:
1360:
1356:
1319:Genome Research
1312:
1311:
1307:
1263:
1262:
1258:
1228:
1227:
1223:
1186:Eukaryotic Cell
1179:
1178:
1174:
1165:
1163:
1149:
1148:
1144:
1114:
1113:
1109:
1065:
1064:
1060:
1030:
1029:
1025:
1012:
1002:
990:
969:
968:
961:
931:
930:
926:
888:
887:
883:
879:
841:
731:
685:immune response
677:
625:
594:N-glycosylation
554:Golgi apparatus
539:
379:
309:plasma membrane
290:
251:minichromosomes
249:chromosomes or
105:
32:
12:
11:
5:
2364:
2362:
2354:
2353:
2348:
2343:
2333:
2332:
2329:
2328:
2323:
2311:
2310:External links
2308:
2306:
2305:
2256:
2221:
2186:
2135:
2099:
2070:(11): 1393β8.
2050:
1988:
1931:
1896:
1845:
1810:
1761:
1742:(10): 607β12.
1726:
1683:
1632:
1583:
1548:
1488:
1438:
1419:(11): 517β20.
1403:
1354:
1325:(9): 1344β52.
1305:
1276:(9): 4018β21.
1256:
1221:
1172:
1142:
1107:
1058:
1023:
1014:|journal=
988:
959:
924:
897:(3): 393β417.
880:
878:
875:
874:
873:
868:
863:
858:
853:
848:
840:
837:
786:immunoreactive
763:phosphorylated
730:
727:
679:VSG is highly
676:
673:
624:
621:
589:transamination
581:N-glycosylated
565:trans-splicing
538:
535:
378:
375:
350:The VSGs from
348:
347:
343:
328:
289:
283:
237:)) located in
172:
171:
168:
167:
162:
158:
157:
152:
148:
147:
139:
138:
133:
127:
126:
123:
119:
118:
115:
111:
110:
103:
99:
98:
94:
93:
85:
84:
77:
71:
70:
66:
65:
60:
54:
53:
50:
46:
45:
42:
38:
37:
30:
26:
25:
21:
20:
13:
10:
9:
6:
4:
3:
2:
2363:
2352:
2349:
2347:
2346:Glycoproteins
2344:
2342:
2339:
2338:
2336:
2327:
2324:
2321:
2317:
2314:
2313:
2309:
2301:
2297:
2292:
2287:
2283:
2279:
2275:
2271:
2267:
2260:
2257:
2252:
2248:
2244:
2240:
2236:
2232:
2225:
2222:
2217:
2213:
2209:
2205:
2201:
2197:
2190:
2187:
2182:
2178:
2173:
2168:
2163:
2158:
2154:
2150:
2146:
2139:
2136:
2131:
2127:
2123:
2119:
2115:
2111:
2103:
2100:
2095:
2091:
2086:
2081:
2077:
2073:
2069:
2065:
2061:
2054:
2051:
2046:
2042:
2037:
2032:
2027:
2022:
2018:
2014:
2010:
2006:
2002:
1995:
1993:
1989:
1984:
1980:
1975:
1970:
1966:
1962:
1958:
1954:
1950:
1946:
1942:
1935:
1932:
1927:
1923:
1919:
1915:
1912:(1): 227β31.
1911:
1907:
1900:
1897:
1892:
1888:
1884:
1880:
1876:
1872:
1868:
1864:
1860:
1856:
1849:
1846:
1841:
1837:
1833:
1829:
1826:(1): 141β60.
1825:
1821:
1814:
1811:
1806:
1802:
1797:
1792:
1788:
1784:
1780:
1776:
1772:
1765:
1762:
1757:
1753:
1749:
1745:
1741:
1737:
1730:
1727:
1722:
1718:
1714:
1710:
1706:
1702:
1699:(3): 287β95.
1698:
1694:
1687:
1684:
1679:
1675:
1670:
1665:
1660:
1655:
1651:
1647:
1643:
1636:
1633:
1628:
1624:
1619:
1614:
1610:
1606:
1603:(1): 136β47.
1602:
1598:
1594:
1587:
1584:
1579:
1575:
1571:
1567:
1563:
1559:
1552:
1549:
1544:
1540:
1535:
1530:
1525:
1520:
1516:
1512:
1509:(10): e3527.
1508:
1504:
1500:
1492:
1489:
1484:
1480:
1476:
1472:
1468:
1464:
1460:
1456:
1449:
1442:
1439:
1434:
1430:
1426:
1422:
1418:
1414:
1407:
1404:
1399:
1395:
1390:
1385:
1381:
1377:
1374:(5): 449β57.
1373:
1369:
1365:
1358:
1355:
1350:
1346:
1341:
1336:
1332:
1328:
1324:
1320:
1316:
1309:
1306:
1301:
1297:
1292:
1287:
1283:
1279:
1275:
1271:
1267:
1260:
1257:
1252:
1248:
1244:
1240:
1236:
1232:
1225:
1222:
1217:
1213:
1208:
1203:
1199:
1195:
1191:
1187:
1183:
1176:
1173:
1162:on 2018-08-31
1161:
1157:
1153:
1146:
1143:
1138:
1134:
1130:
1126:
1122:
1118:
1111:
1108:
1103:
1099:
1094:
1089:
1085:
1081:
1077:
1073:
1069:
1062:
1059:
1054:
1050:
1046:
1042:
1038:
1034:
1027:
1024:
1019:
1007:
999:
995:
991:
985:
981:
977:
973:
966:
964:
960:
955:
951:
947:
943:
940:(3): 329β36.
939:
935:
928:
925:
920:
916:
912:
908:
904:
900:
896:
892:
885:
882:
876:
872:
869:
867:
864:
862:
859:
857:
854:
852:
849:
846:
843:
842:
838:
836:
833:
829:
825:
821:
820:
814:
812:
811:
805:
803:
799:
795:
791:
787:
783:
782:
777:
773:
772:
766:
764:
760:
759:T. equiperdum
756:
751:
747:
746:
740:
738:
737:
728:
726:
723:
719:
714:
710:
709:cell division
706:
703:
700:
696:
695:
690:
686:
682:
674:
667:
663:
661:
656:
654:
653:alpha helices
649:
645:
641:
638:
634:
630:
622:
620:
618:
612:
610:
606:
602:
597:
595:
590:
586:
582:
578:
574:
570:
566:
562:
557:
555:
551:
547:
543:
536:
529:
525:
523:
518:
516:
511:
509:
505:
501:
496:
494:
490:
486:
485:recombination
482:
478:
473:
469:
464:
461:
458:found at the
457:
453:
449:
445:
441:
440:development.
439:
435:
431:
427:
423:
419:
415:
411:
407:
403:
399:
396:; others are
395:
391:
388:
384:
376:
374:
372:
368:
363:
361:
357:
353:
344:
341:
337:
333:
329:
326:
322:
318:
314:
310:
306:
305:
304:
301:
299:
295:
288:
284:
282:
280:
275:
272:
268:
264:
260:
256:
252:
248:
244:
240:
236:
228:
223:
219:
217:
213:
209:
205:
204:
199:
198:
193:
190:
186:
182:
178:
166:
163:
159:
156:
153:
149:
144:
140:
137:
134:
132:
128:
124:
120:
116:
112:
108:
104:
100:
95:
90:
83:
82:
78:
76:
72:
67:
64:
61:
59:
55:
52:Tb05.26C7.380
51:
47:
43:
39:
35:
31:
27:
22:
17:
2276:(1): 33β45.
2273:
2269:
2259:
2237:(2): 300β6.
2234:
2230:
2224:
2199:
2195:
2189:
2152:
2148:
2138:
2116:(1β2): 1β8.
2113:
2109:
2102:
2067:
2063:
2053:
2008:
2004:
1948:
1944:
1934:
1909:
1905:
1899:
1858:
1854:
1848:
1823:
1819:
1813:
1778:
1774:
1764:
1739:
1736:Glycobiology
1735:
1729:
1696:
1692:
1686:
1649:
1646:BMC Genomics
1645:
1635:
1600:
1596:
1586:
1561:
1557:
1551:
1506:
1502:
1491:
1458:
1454:
1441:
1416:
1412:
1406:
1371:
1367:
1357:
1322:
1318:
1308:
1273:
1269:
1259:
1234:
1230:
1224:
1192:(1): 76β83.
1189:
1185:
1175:
1164:. Retrieved
1160:the original
1155:
1145:
1120:
1116:
1110:
1075:
1071:
1061:
1036:
1032:
1026:
971:
937:
933:
927:
894:
891:Parasitology
890:
884:
823:
817:
815:
808:
806:
804:infections.
801:
779:
769:
767:
758:
754:
743:
741:
734:
732:
721:
717:
692:
678:
657:
626:
613:
608:
601:calreticulin
598:
585:GPI anchored
567:directed by
558:
541:
540:
521:
519:
514:
512:
503:
497:
476:
471:
467:
465:
451:
443:
442:
433:
429:
425:
421:
417:
416:or 'mosaic'
409:
404:, premature
386:
382:
380:
364:
351:
349:
321:transporters
317:ion channels
302:
293:
291:
286:
276:
243:subtelomeric
232:
226:
208:George Cross
201:
195:
185:cell surface
180:
176:
175:
122:Alt. symbols
79:
49:Alt. symbols
44:Tb927.5.4730
2202:(1): 1β11.
1951:(1): 11β7.
1039:(2): 53β8.
828:glucosamine
736:Trypanosoma
681:immunogenic
644:amino acids
542:Trypanosoma
508:nucleosomes
481:pseudogenes
406:stop codons
398:pseudogenes
255:polycistron
245:arrays (on
235:pseudogenes
218:activity.
216:biochemical
206:in 1975 by
197:Trypanosoma
155:Swiss-model
97:Identifiers
24:Identifiers
2335:Categories
1166:2013-07-28
877:References
856:Glycocalyx
648:C terminal
637:N terminal
633:structural
489:DNA repair
377:Expression
371:tsetse fly
367:procyclins
336:stochastic
151:Structures
146:Search for
75:Chromosome
69:Other data
1123:: 47β62.
1016:ignored (
1006:cite book
802:T. evansi
761:are also
739:species.
722:T. brucei
683:, and an
623:Structure
577:polysomes
522:T. brucei
515:T. brucei
460:telomeres
387:T. brucei
352:T. brucei
330:Periodic
325:receptors
315:(such as
239:telomeric
192:parasites
189:protozoan
2300:19748930
2181:15377385
2155:(1): 3.
2130:22277627
1983:22954210
1805:27110662
1756:12244073
1678:17629915
1627:19915073
1578:11334937
1543:18953401
1503:PLOS ONE
1483:26552797
1475:19751359
1433:16126458
1398:10998374
1349:17652423
1251:16291721
1216:12582124
1137:22023441
1102:20765166
1053:15275499
998:11461029
919:20749130
839:See also
824:in vitro
694:in vitro
689:Antibody
629:sequence
605:calnexin
550:lysosome
477:T.brucei
414:chimeric
313:epitopes
263:promoter
247:megabase
165:InterPro
102:Organism
29:Organism
2291:2794310
2251:6470988
2216:8943146
2094:6821334
2045:6308614
2013:Bibcode
1974:3467770
1953:Bibcode
1926:9252591
1891:4370099
1883:8464512
1863:Bibcode
1840:2231728
1796:5575760
1713:6736139
1669:1934917
1652:: 234.
1618:2805301
1534:2567434
1511:Bibcode
1389:2627965
1340:1950903
1300:2779574
1093:2331906
954:6530143
845:Amastin
832:mannose
718:in vivo
713:progeny
438:vaccine
360:monomer
161:Domains
131:UniProt
125:VSG 221
63:3657576
2322:(MeSH)
2298:
2288:
2249:
2214:
2179:
2172:521498
2169:
2128:
2092:
2085:553222
2082:
2043:
2036:384026
2033:
1981:
1971:
1924:
1889:
1881:
1855:Nature
1838:
1803:
1793:
1754:
1719:
1711:
1676:
1666:
1625:
1615:
1576:
1541:
1531:
1481:
1473:
1431:
1396:
1386:
1347:
1337:
1298:
1291:362464
1288:
1249:
1214:
1207:141176
1204:
1135:
1100:
1090:
1051:
996:
986:
952:
917:
909:
720:. As
640:domain
552:, and
448:silent
390:genome
298:dimers
136:P26332
114:Symbol
58:Entrez
41:Symbol
1887:S2CID
1721:73535
1717:S2CID
1479:S2CID
1451:(PDF)
915:S2CID
790:ELISA
776:surra
705:assay
702:lysis
697:by a
573:3'UTR
394:genes
2296:PMID
2247:PMID
2212:PMID
2177:PMID
2126:PMID
2090:PMID
2041:PMID
1979:PMID
1949:1267
1922:PMID
1879:PMID
1836:PMID
1801:PMID
1752:PMID
1709:PMID
1674:PMID
1623:PMID
1574:PMID
1539:PMID
1471:PMID
1429:PMID
1394:PMID
1345:PMID
1296:PMID
1247:PMID
1212:PMID
1133:PMID
1098:PMID
1049:PMID
1018:help
994:PMID
984:ISBN
950:PMID
934:Gene
907:PMID
830:and
563:and
456:loci
241:and
225:The
2286:PMC
2278:doi
2239:doi
2204:doi
2167:PMC
2157:doi
2118:doi
2114:187
2080:PMC
2072:doi
2031:PMC
2021:doi
1969:PMC
1961:doi
1914:doi
1910:153
1871:doi
1859:362
1828:doi
1824:216
1791:PMC
1783:doi
1744:doi
1701:doi
1664:PMC
1654:doi
1613:PMC
1605:doi
1566:doi
1529:PMC
1519:doi
1463:doi
1421:doi
1384:PMC
1376:doi
1335:PMC
1327:doi
1286:PMC
1278:doi
1239:doi
1235:118
1202:PMC
1194:doi
1125:doi
1088:PMC
1080:doi
1041:doi
976:doi
942:doi
911:645
899:doi
816:In
798:PCR
742:In
617:PLC
472:VSG
468:VSG
452:VSG
444:VSG
434:VSG
430:VSG
426:VSG
422:VSG
418:VSG
410:VSG
383:VSG
292:In
285:In
257:by
187:of
181:VSG
117:N/A
2337::
2294:.
2284:.
2274:27
2272:.
2268:.
2245:.
2235:31
2233:.
2210:.
2200:82
2198:.
2175:.
2165:.
2151:.
2147:.
2124:.
2112:.
2088:.
2078:.
2066:.
2062:.
2039:.
2029:.
2019:.
2009:80
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