Glycosylation Focuses Sequence Variation in the Influenza A Virus H1 Hemagglutinin Globular Domain


Antigenic drift in the influenza A virus hemagglutinin (HA) is responsible for seasonal reformulation of influenza vaccines. Here, we address an important and largely overlooked issue in antigenic drift: how does the number and location of glycosylation sites affect HA evolution in man? We analyzed the glycosylation status of all full-length H1 subtype HA sequences available in the NCBI influenza database. We devised the “flow index” (FI), a simple algorithm that calculates the tendency for viruses to gain or lose consensus glycosylation sites. The FI predicts the predominance of glycosylation states among existing strains. Our analyses show that while the number of glycosylation sites in the HA globular domain does not influence the overall magnitude of variation in defined antigenic regions, variation focuses on those regions unshielded by glycosylation. This supports the conclusion that glycosylation generally shields HA from antibody-mediated neutralization, and implies that fitness costs in accommodating oligosaccharides limit virus escape via HA hyperglycosylation.


Vyšlo v časopise: Glycosylation Focuses Sequence Variation in the Influenza A Virus H1 Hemagglutinin Globular Domain. PLoS Pathog 6(11): e32767. doi:10.1371/journal.ppat.1001211
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001211

Souhrn

Antigenic drift in the influenza A virus hemagglutinin (HA) is responsible for seasonal reformulation of influenza vaccines. Here, we address an important and largely overlooked issue in antigenic drift: how does the number and location of glycosylation sites affect HA evolution in man? We analyzed the glycosylation status of all full-length H1 subtype HA sequences available in the NCBI influenza database. We devised the “flow index” (FI), a simple algorithm that calculates the tendency for viruses to gain or lose consensus glycosylation sites. The FI predicts the predominance of glycosylation states among existing strains. Our analyses show that while the number of glycosylation sites in the HA globular domain does not influence the overall magnitude of variation in defined antigenic regions, variation focuses on those regions unshielded by glycosylation. This supports the conclusion that glycosylation generally shields HA from antibody-mediated neutralization, and implies that fitness costs in accommodating oligosaccharides limit virus escape via HA hyperglycosylation.


Zdroje

1. SkehelJJ

WileyDC

2000 Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 69 531 569

2. RussG

BenninkJR

BachiT

YewdellJW

1991 Influenza virus hemagglutinin trimers and monomers maintain distinct biochemical modifications and intracellular distribution in brefeldin A-treated cells. Cell Regul 2 549 563

3. YewdellJW

YellenA

BachiT

1988 Monoclonal antibodies localize events in the folding, assembly, and intracellular transport of the influenza virus hemagglutinin glycoprotein. Cell 52 843 852

4. DanielsR

KurowskiB

JohnsonAE

HebertDN

2003 N-linked glycans direct the cotranslational folding pathway of influenza hemagglutinin. Mol Cell 11 79 90

5. WilsonIA

SkehelJJ

WileyDC

1981 Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature 289 366 373

6. WileyDC

WilsonIA

SkehelJJ

1981 Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 289 373 378

7. GerhardW

YewdellJ

FrankelME

WebsterR

1981 Antigenic structure of influenza virus haemagglutinin defined by hybridoma antibodies. Nature 290 713 717

8. YewdellJW

GerhardW

1981 Antigenic characterization of viruses by monoclonal antibodies. Annu Rev Microbiol 35 185 206

9. CatonAJ

BrownleeGG

YewdellJW

GerhardW

1982 The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell 31 417 427

10. WileyDC

SkehelJJ

1987 The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annual Reviews in Biochemistry 56 365 394

11. ZhangM

GaschenB

BlayW

FoleyB

HaigwoodN

2004 Tracking global patterns of N-linked glycosylation site variation in highly variable viral glycoproteins: HIV, SIV, and HCV envelopes and influenza hemagglutinin. Glycobiology 14 1229 1246

12. VigerustDJ

ShepherdVL

2007 Virus glycosylation: role in virulence and immune interactions. Trends Microbiol 15 211 218

13. TsuchiyaE

SugawaraK

HongoS

MatsuzakiY

MurakiY

2002 Effect of addition of new oligosaccharide chains to the globular head of influenza A/H2N2 virus haemagglutinin on the intracellular transport and biological activities of the molecule. J Gen Virol 83 1137 1146

14. SchulzeIT

1997 Effects of glycosylation on the properties and functions of influenza virus hemagglutinin. J Infect Dis 176 Suppl 1 S24 28

15. Mir-ShekariSY

AshfordDA

HarveyDJ

DwekRA

SchulzeIT

1997 The glycosylation of the influenza A virus hemagglutinin by mammalian cells. A site-specific study. J Biol Chem 272 4027 4036

16. IgarashiM

ItoK

KidaH

TakadaA

2008 Genetically destined potentials for N-linked glycosylation of influenza virus hemagglutinin. Virology 376 323 329

17. CherryJL

LipmanDJ

NikolskayaA

WolfYI

2009 Evolutionary dynamics of N-glycosylation sites of influenza virus hemagglutinin. PLoS Curr Influenza RRN1001

18. DeshpandeKL

FriedVA

AndoM

WebsterRG

1987 Glycosylation affects cleavage of an H5N2 influenza virus hemagglutinin and regulates virulence. Proc Natl Acad Sci U S A 84 36 40

19. WangCC

ChenJR

TsengYC

HsuCH

HungYF

2009 Glycans on influenza hemagglutinin affect receptor binding and immune response. Proc Natl Acad Sci U S A 106 18137 18142

20. WagnerR

HeuerD

WolffT

HerwigA

KlenkHD

2002 N-Glycans attached to the stem domain of haemagglutinin efficiently regulate influenza A virus replication. J Gen Virol 83 601 609

21. Ben-DorS

EstermanN

RubinE

SharonN

2004 Biases and complex patterns in the residues flanking protein N-glycosylation sites. Glycobiology 14 95 101

22. PetrescuAJ

MilacAL

PetrescuSM

DwekRA

WormaldMR

2004 Statistical analysis of the protein environment of N-glycosylation sites: implications for occupancy, structure, and folding. Glycobiology 14 103 114

23. BreuerW

KleinRA

HardtB

BartoschekA

BauseE

2001 Oligosaccharyltransferase is highly specific for the hydroxy amino acid in Asn-Xaa-Thr/Ser. FEBS Lett 501 106 110

24. KasturiL

EshlemanJR

WunnerWH

Shakin-EshlemanSH

1995 The hydroxy amino acid in an Asn-X-Ser/Thr sequon can influence N-linked core glycosylation efficiency and the level of expression of a cell surface glycoprotein. J Biol Chem 270 14756 14761

25. EdgarRC

2004 MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32 1792 1797

26. GallagherPJ

HenneberryJM

SambrookJF

GethingMJ

1992 Glycosylation requirements for intracellular transport and function of the hemagglutinin of influenza virus. J Virol 66 7136 7145

27. GallagherP

HenneberryJ

WilsonI

SambrookJ

GethingMJ

1988 Addition of carbohydrate side chains at novel sites on influenza virus hemagglutinin can modulate the folding, transport, and activity of the molecule. J Cell Biol 107 2059 2073

28. KlenkHD

WagnerR

HeuerD

WolffT

2002 Importance of hemagglutinin glycosylation for the biological functions of influenza virus. Virus Res 82 73 75

29. OhuchiR

OhuchiM

GartenW

KlenkHD

1997 Oligosaccharides in the stem region maintain the influenza virus hemagglutinin in the metastable form required for fusion activity. J Virol 71 3719 3725

30. HebertDN

FoellmerB

HeleniusA

1996 Calnexin and calreticulin promote folding, delay oligomerization and suppress degradation of influenza hemagglutinin in microsomes. EMBO J 15 2961 2968

31. StevensJ

BlixtO

TumpeyTM

TaubenbergerJK

PaulsonJC

2006 Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Science 312 404 410

32. NichollsJM

ChanRW

RussellRJ

AirGM

PeirisJS

2008 Evolving complexities of influenza virus and its receptors. Trends Microbiol 16 149 157

33. GartenRJ

DavisCT

RussellCA

ShuB

LindstromS

2009 Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science 325 197 201

34. ItohY

ShinyaK

KisoM

WatanabeT

SakodaY

2009 In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 460 1021 1025

35. NeumannG

NodaT

KawaokaY

2009 Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature 459 931 939

36. WeiCJ

BoyingtonJC

DaiK

HouserKV

PearceMB

Cross-neutralization of 1918 and 2009 influenza viruses: role of glycans in viral evolution and vaccine design. Sci Transl Med 2 24ra21

37. FrancisT

SalkJE

QuilliganJJ

1947 Experience with Vaccination Against Influenza in the Spring of 1947: A Preliminary Report. Am J Public Health Nations Health 37 1013 1016

38. FrancisTJr

1947 Apparent serological variation within a strain of influenza virus. Proc Soc Exp Biol Med 65 143 147

39. SkehelJJ

StevensDJ

DanielsRS

DouglasAR

KnossowM

1984 A carbohydrate side chain on hemagglutinins of Hong Kong influenza viruses inhibits recognition by a monoclonal antibody. Proc Natl Acad Sci U S A 81 1779 1783

40. XuR

EkiertDC

KrauseJC

HaiR

CroweJEJr

Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus. Science

41. BlackburneBP

HayAJ

GoldsteinRA

2008 Changing selective pressure during antigenic changes in human influenza H3. PLoS Pathog 4 e1000058

42. TamuriAU

Dos ReisM

HayAJ

GoldsteinRA

2009 Identifying changes in selective constraints: host shifts in influenza. PLoS Comput Biol 5 e1000564

43. GambaryanAS

RobertsonJS

MatrosovichMN

1999 Effects of egg-adaptation on the receptor-binding properties of human influenza A and B viruses. Virology 258 232 239

44. WessaP

2008 Bootstrap Plot for Central Tendency (v1.0.3) in Free Statistics Software (v1.1.23-r6), Office for Research Development and Education. URL http://www.wessa.net/rwasp_bootstrapplot1.wasp/

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2010 Číslo 11
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Eozinofilní granulomatóza s polyangiitidou
nový kurz
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa