TLR4 896A/G and TLR9 1174G/A Polymorphisms Are Associated with the Risk of Infectious Mononucleosis

Overview

Journal Sci Rep

Specialty Science

Date 2020 Aug 6

PMID 32753695

Citations 14

Authors

Agnieszka Jablonska

Miroslawa Studzinska

Leszek Szenborn

Malgorzata Wisniewska-Ligier

Monika Karlikowska-Skwarnik

Tomasz Gesicki

Edyta Paradowska

Affiliations

Soon will be listed here.

Abstract

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and activate innate and adaptive immune responses. Single nucleotide polymorphisms (SNPs) within the TLR genes may influence host-pathogen interactions and can have an impact on the progression of infectious diseases. The present study aimed to investigate the genotype distribution of TLR2 (2029C/T, rs121917864; 2258G/A, rs5743708), TLR4 (896A/G, rs4986790), and TLR9 (- 1237T/C, rs5743836; - 1486T/C, rs187084; 1174G/A, rs352139; and 2848C/T, rs352140) polymorphisms in 149 children and adolescents with infectious mononucleosis (IM) and 140 healthy individuals. The potential association of TLR SNPs with the clinical manifestations of EBV infection was also studied. The presence of TLR2, TLR4, and TLR9 SNPs was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). EBV DNA loads were detected by quantitative real-time PCR assay. The TLR4 896 GG and the TLR9 1174 GA genotypes were associated with an increased risk of EBV-related IM in examined patients (p = 0.014 and p = 0.001, respectively). The heterozygous genotype of the TLR4 896A/G SNP was associated with an increased risk of elevated liver enzyme levels and leukocytosis (p < 0.05). Our preliminary study revealed that the TLR4 896A/G and the TLR9 1174G/A polymorphisms seem to be related to the course of acute EBV infection in children and adolescents.

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References

Stock I . [Infectious mononucleosis--a "childhood disease" of great medical concern]. Med Monatsschr Pharm. 2013; 36(10):364-8. View

Macsween K, Crawford D . Epstein-Barr virus-recent advances. Lancet Infect Dis. 2003; 3(3):131-40. DOI: 10.1016/s1473-3099(03)00543-7. View

Balfour Jr H, Odumade O, Schmeling D, Mullan B, Ed J, Knight J . Behavioral, virologic, and immunologic factors associated with acquisition and severity of primary Epstein-Barr virus infection in university students. J Infect Dis. 2012; 207(1):80-8. PMC: 3523797. DOI: 10.1093/infdis/jis646. View

Rea T, Russo J, Katon W, Ashley R, Buchwald D . Prospective study of the natural history of infectious mononucleosis caused by Epstein-Barr virus. J Am Board Fam Pract. 2001; 14(4):234-42. View

Hadinoto V, Shapiro M, Greenough T, Sullivan J, Luzuriaga K, Thorley-Lawson D . On the dynamics of acute EBV infection and the pathogenesis of infectious mononucleosis. Blood. 2007; 111(3):1420-7. PMC: 2214734. DOI: 10.1182/blood-2007-06-093278. View

Kurth J, Spieker T, Wustrow J, Strickler G, Hansmann L, Rajewsky K . EBV-infected B cells in infectious mononucleosis: viral strategies for spreading in the B cell compartment and establishing latency. Immunity. 2000; 13(4):485-95. DOI: 10.1016/s1074-7613(00)00048-0. View

Maeda E, Akahane M, Kiryu S, Kato N, Yoshikawa T, Hayashi N . Spectrum of Epstein-Barr virus-related diseases: a pictorial review. Jpn J Radiol. 2009; 27(1):4-19. DOI: 10.1007/s11604-008-0291-2. View

Young L, Rickinson A . Epstein-Barr virus: 40 years on. Nat Rev Cancer. 2004; 4(10):757-68. DOI: 10.1038/nrc1452. View

Hjalgrim H, Smedby K, Rostgaard K, Molin D, Hamilton-Dutoit S, Chang E . Infectious mononucleosis, childhood social environment, and risk of Hodgkin lymphoma. Cancer Res. 2007; 67(5):2382-8. DOI: 10.1158/0008-5472.CAN-06-3566. View

10.

Hjalgrim H, Askling J, Rostgaard K, Hamilton-Dutoit S, Frisch M, Zhang J . Characteristics of Hodgkin's lymphoma after infectious mononucleosis. N Engl J Med. 2003; 349(14):1324-32. DOI: 10.1056/NEJMoa023141. View

11.

Ogembo J, Kannan L, Ghiran I, Nicholson-Weller A, Finberg R, Tsokos G . Human complement receptor type 1/CD35 is an Epstein-Barr Virus receptor. Cell Rep. 2013; 3(2):371-85. PMC: 3633082. DOI: 10.1016/j.celrep.2013.01.023. View

12.

Gaudreault E, Fiola S, Olivier M, Gosselin J . Epstein-Barr virus induces MCP-1 secretion by human monocytes via TLR2. J Virol. 2007; 81(15):8016-24. PMC: 1951286. DOI: 10.1128/JVI.00403-07. View

13.

Tanner J, Weis J, Fearon D, Whang Y, Kieff E . Epstein-Barr virus gp350/220 binding to the B lymphocyte C3d receptor mediates adsorption, capping, and endocytosis. Cell. 1987; 50(2):203-13. DOI: 10.1016/0092-8674(87)90216-9. View

14.

Fingeroth J, Weis J, Tedder T, Strominger J, Biro P, Fearon D . Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2. Proc Natl Acad Sci U S A. 1984; 81(14):4510-4. PMC: 345620. DOI: 10.1073/pnas.81.14.4510. View

15.

Ariza M, Glaser R, Kaumaya P, Jones C, Williams M . The EBV-encoded dUTPase activates NF-kappa B through the TLR2 and MyD88-dependent signaling pathway. J Immunol. 2009; 182(2):851-9. DOI: 10.4049/jimmunol.182.2.851. View

16.

Valente R, Ehlers E, Xu D, Ahmad H, Steadman A, Blasnitz L . Toll-like receptor 7 stimulates the expression of Epstein-Barr virus latent membrane protein 1. PLoS One. 2012; 7(8):e43317. PMC: 3432040. DOI: 10.1371/journal.pone.0043317. View

17.

Fiola S, Gosselin D, Takada K, Gosselin J . TLR9 contributes to the recognition of EBV by primary monocytes and plasmacytoid dendritic cells. J Immunol. 2010; 185(6):3620-31. DOI: 10.4049/jimmunol.0903736. View

18.

Lim W, Kireta S, Russ G, Coates P . Human plasmacytoid dendritic cells regulate immune responses to Epstein-Barr virus (EBV) infection and delay EBV-related mortality in humanized NOD-SCID mice. Blood. 2006; 109(3):1043-50. DOI: 10.1182/blood-2005-12-024802. View

19.

Paradowska E, Jablonska A, Studzinska M, Skowronska K, Suski P, Wisniewska-Ligier M . TLR9 -1486T/C and 2848C/T SNPs Are Associated with Human Cytomegalovirus Infection in Infants. PLoS One. 2016; 11(4):e0154100. PMC: 4841553. DOI: 10.1371/journal.pone.0154100. View

20.

Taniguchi R, Koyano S, Suzutani T, Goishi K, Ito Y, Morioka I . Polymorphisms in TLR-2 are associated with congenital cytomegalovirus (CMV) infection but not with congenital CMV disease. Int J Infect Dis. 2013; 17(12):e1092-7. DOI: 10.1016/j.ijid.2013.06.004. View