Induction of a Peptide with Activity against a Broad Spectrum of Pathogens in the Salivary Gland, following Infection with Dengue Virus

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The ultimate stage of the transmission of Dengue Virus (DENV) to man is strongly dependent on crosstalk between the virus and the immune system of its vector Aedes aegypti (Ae. aegypti). Infection of the mosquito's salivary glands by DENV is the final step prior to viral transmission. Therefore, in the present study, we have determined the modulatory effects of DENV infection on the immune response in this organ by carrying out a functional genomic analysis of uninfected salivary glands and salivary glands of female Ae. aegypti mosquitoes infected with DENV. We have shown that DENV infection of salivary glands strongly up-regulates the expression of genes that encode proteins involved in the vector's innate immune response, including the immune deficiency (IMD) and Toll signalling pathways, and that it induces the expression of the gene encoding a putative anti-bacterial, cecropin-like, peptide (AAEL000598). Both the chemically synthesized non-cleaved, signal peptide-containing gene product of AAEL000598, and the cleaved, mature form, were found to exert, in addition to antibacterial activity, anti-DENV and anti-Chikungunya viral activity. However, in contrast to the mature form, the immature cecropin peptide was far more effective against Chikungunya virus (CHIKV) and, furthermore, had strong anti-parasite activity as shown by its ability to kill Leishmania spp. Results from circular dichroism analysis showed that the immature form more readily adopts a helical conformation which would help it to cause membrane permeabilization, thus permitting its transfer across hydrophobic cell surfaces, which may explain the difference in the anti-pathogenic activity between the two forms. The present study underscores not only the importance of DENV-induced cecropin in the innate immune response of Ae. aegypti, but also emphasizes the broad-spectrum anti-pathogenic activity of the immature, signal peptide-containing form of this peptide.

Vyšlo v časopise: Induction of a Peptide with Activity against a Broad Spectrum of Pathogens in the Salivary Gland, following Infection with Dengue Virus. PLoS Pathog 7(1): e32767. doi:10.1371/journal.ppat.1001252
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001252

Souhrn

Zdroje

1. Anonymous

2009 Dengue and dengue hemorrhagic fever Geneva World Health Organization

2. SrikiatkhachornA

GreenS

2010 Markers of dengue disease severity. Curr Top Microbiol Immunol 338 67 82

3. LuplertlopN

MisséD

BrayD

DeleuzeV

GonzalezJP

2006 Dengue-virus-infected dendritic cells trigger vascular leakage through metalloproteinase overproduction. EMBO Rep 7 1176 1181

4. SalazarMI

RichardsonJH

Sanchez-VargasI

OlsonKE

BeatyBJ

2007 Dengue virus type 2: replication and tropisms in orally infected Aedes aegypti mosquitoes. BMC Microbiol 7 9

5. HoffmannJA

KafatosFC

JanewayCA

EzekowitzRA

1999 Phylogenetic perspectives in innate immunity. Science 284 1313 1318

6. IpYT

ReachM

EngstromY

KadalayilL

CaiH

1993 Dif a dorsal-related gene that mediates an immune response in Drosophila. Cell 75 753 763

7. Sanchez-VargasI

ScottJC

Poole-SmithBK

FranzAWE

Barbosa-SolomieuV

2009 Dengue virus type 2 infections of Aedes aegypti are modulated by the mosquito's RNA interference pathway. PLoS Pathog 5 e1000299

8. XiZ

RamirezJL

DimopoulosG

2008 The Aedes aegypti toll pathway controls dengue virus infection. PLoS Pathog 4 e1000098

9. Souza-NetoJA

SimS

DimopoulosG

2009 An evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense. Proc Natl Acad Sci USA 106 17841 17846

10. NeneV

WortmanJR

LawsonD

HaasB

KodiraC

2007 Genome sequence of Aedes aegypti, a major arbovirus vector. Science 316 1718 1723

11. CalvoE

PhamVM

MarinottiO

AndersenJF

RibeiroJM

2009 The salivary gland transcriptome of the neotropical malaria vector Anopheles darlingi reveals accelerated evolution of genes relevant to hematophagy. BMC Genomics 29 10 57

12. RibeiroJM

ArcàB

LombardoF

CalvoE

PhanVM

2007 An annotated catalogue of salivary gland transcripts in the adult female mosquito, Aedes aegypti. BMC Genomics 8 6

13. ZivkovicZ

TorinaA

MitraR

AlongiA

ScimecaS

2010 Subolesin expression in response to pathogen infection in ticks. BMC Immunol 19 11 17

14. CampbellCL

VandykeKA

LetchworthGJ

DroletBS

HanekampT

2005 Midgut and salivary gland transcriptomes of the arbovirus vector Culicoides sonorensis (Diptera: Ceratopogonidae). Insect Mol Biol 14 121 136

15. Rosinski-ChupinI

BriolayJ

BrouillyP

PerrotS

GomezSM

2007 SAGE analysis of mosquito salivary gland transcriptomes during Plasmodium invasion. Cell Microbiol 9 708 724

16. HalsteadSB

SimasthienP

1970 Observations related to the pathogenesis of dengue hemorrhagic fever. II.Antigenic and biologic properties of dengue viruses and their association with disease response in the host. Yale J Biol Med 42 276 292

17. YaoH

FangM

ZhaoW

DuanF

LinL

2003 NS2A-NS2B sequence analysis of DEN-4 virus strains. Southeast Asian J Trop Med Public Health 34 554 558

18. MacdonaldWW

1963 Further studies on a strain of Aedes aegypti susceptible to infection with sub-periodic Brugia malayi. Ann Trop Med Parasitol 57 452 460

19. AltoBW

LounibosLP

HiggsS

JulianoSA

2005 Larval competition differentially affects arbovirus infection in Aedes mosquitoes. Ecology 86 3279 3288

20. PiquemalD

CommesT

ManchonL

2002 Transcriptome analysis of monocytic leukemia cell differentiation. Genomics 80 361 371

21. Leparc-GoffartI

BaragattiM

TemmamS

TuiskunenA

MoureauG

2009 Development and validation of real-time one-step reverse transcription-PCR for the detection and typing of dengue viruses. J Clin Virol 45 6166

22. WasinpiyamongkolL

PatramoolS

LuplertlopN

SurasombatpattanaP

DoucouréS

2010 Blood-feeding and immunogenic Aedes aegypti saliva proteins. Proteomics 10 1 11

23. MisséD

YsselH

TrabattoniD

ObletC

Lo CaputoS

2007 IL-22 participates in an innate anti-HIV-1 host-resistance network through acute-phase protein induction. J Immunol 178 407 15

24. WuJM

JanPS

YuHC

HaungHY

FangHJ

2009 Structure and function of a custom anticancer peptide, CB1a. Peptides 30 839 848

25. SerenoD

RoyG

LemesreJL

PapadopoulouB

OuelletteM

2001 DNA transformation of Leishmania infantum axenic amastigotes and their use in drug screening. Antimicrob Agents Chemother 45 1168 73

26. AbbassiF

OuryB

BlascoT

SerenoD

BolbachG

2008 Isolation, characterization and molecular cloning of new temporins from the skin of the North African ranid Pelophylax saharica. Peptides 29 1526 1533

27. EkengrenS

HultmarkD

1999 Drosophila cecropin as an antifungal agent. Insect Biochem Mol Biol 29 965 972

28. SolignatM

GayB

HiggsS

BriantL

DevauxC

2009 Replication cycle of chikungunya: a re-emerging arbovirus. Virology 393 183 197

29. BernardE

SolignatM

GayB

ChazalN

HiggsS

2010 Endocytosis of chickungunya virus into mammalian cells: role of clathrin and early endosomal compartments. PLoS One 5 e11479

30. ResendeJM

MoraesCM

MunhozVH

AisenbreyC

VerlyRM

2009 Membrane structure and conformational changes of the antibiotic heterodimeric peptide distinction by solid-state NMR spectroscopy. Proc Natl Acad Sci USA 10 16639 16644

31. ChoeKM

WernerT

StövenS

HultmarkD

AndersonKV

2002 Requirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila. Science 296 359 362

32. CalvoE

MansBJ

RibeiroJM

AndersenJF

2009 Multifunctionality and mechanism of ligand binding in a mosquito antiinflammatory protein. Proc Natl Acad Sci USA 106 3728 3733

33. HarizanovaN

GeorgievaT

DunkovBC

YoshigaT

LawJH

2005 Aedes aegypti transferrin. Gene structure, expression pattern, and regulation. Insect Mol Biol 14 79 88

34. ChenJ

SunM

LeeS

ZhouG

RowleyJD

2002 Identifying novel transcripts and novel genes in the human genome by using novel SAGE tags. Proc Natl Acad Sci USA 99 12257 1262

35. DubrulleM

MoussonL

MoutaillerS

VazeilleM

FaillouxAB

2009 Chikungunya virus and Aedes mosquitoes: saliva is infectious as soon as two days after oral infection. PLoS One 4 e5895

36. FaranME

RomoserWS

RoutierRG

BaileyCL

1988 The distribution of Rift Valley fever virus in the mosquito Culex pipiens as revealed by viral titration of dissected organs and tissues. Am J Trop Med Hyg 39 206 213

37. GaidamovichSY

KhutoretskayaNV

LvovaAI

SveshnikovaNA

1973 Immuno-fluorescent staining study of the salivary glands of mosquitoes infected with group A arboviruses. Intervirology 1 193 200

38. RamirezJL

DimopoulosG

2010 The Toll immune signaling pathway control conserved anti-dengue defenses across diverse Ae. aegypti strains and against multiple dengue virus serotypes. Dev Comp Immunol 34 625 629

39. TurcoSJ

DescoteauxA

1992 The lipophosphoglycan of Leishmania parasites. Annu Rev Microbiol 46 65 94

40. Díaz-AchiricaP

UbachJ

GuineaA

AndreuD

RivasL

1998 The plasma membrane of Leishmania donovani promastigotes is the main target for CA(1–8)M(1–18), a synthetic cecropin A-melittin hybrid peptide. Biochem J 330 453 60

41. YangL

HarrounTA

WeissTM

DingL

HuangHW

2001 Barrel-stave model or toroidal model? A case study on melittin pores. Biophys J 81 1475 1485

42. BrogdenKA

2005 Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 3 238 250

43. HsiehSC

TsaiWY

WangWK

2010 The length of and nonhydrophobic residues in the transmembrane domain of dengue virus envelope protein are critical for its retention and assembly in the endoplasmic reticulum. J Virol 84 4782 4797

44. KokozaV

AhmedA

Woon ShinS

OkaforN

ZouZ

2010 Blocking of Plasmodium transmission by cooperative action of Cecropin A and Defensin A in transgenic Aedes aegypti mosquitoes. Proc Natl Acad Sci USA 107 8111 8116

45. WachingerM

KleinschmidtA

WinderD

von PechmannN

LudvigsenA

1998 Antimicrobial peptides melittin and cecropin inhibit replication of human immunodeficiency virus 1 by suppressing viral gene expression. J Gen Virol 79 731 740

46. Carballar-LejarazúR

RodríguezMH

de la Cruz Hernández-HernándezF

2008 Recombinant scorpine: a multifunctional antimicrobial peptide with activity against different pathogens. Cell Mol Life Sci 65 3081 3092

47. CallawayJE

LaiJ

HaselbeckB

BaltaianM

BonnesenSP

1993 Modification of the C terminus of cecropin is essential for broad-spectrum antimicrobial activity. Antimicrob Agents Chemother 37 1614 1619

48. PlunkettRM

MurraySI

LowenbergerCA

2009 Generation and characterization of the antibacterial activity of a novel hybrid antimicrobial peptide comprising functional domains from different insect cecropins. Can J Microbiol 55 520 528

49. MorensDM

FolkersGK

FauciAS

2004 The challenge of emerging and re-emerging infectious diseases. Nature 430 242 249

50. GottarM

GobertV

MichelT

BelvinM

DuykG

2002 The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein. Nature 416 640 644

51. SchmidtRL

TrejoTR