Investigation of the impact of AXL, TLR3, and STAT2 in congenital Zika syndrome through genetic polymorphisms and protein-protein interaction network analyses

Birth Defects Res. 2023 Oct 1;115(16):1500-1512. doi: 10.1002/bdr2.2232. Epub 2023 Aug 1.

Abstract

Introduction: Zika virus (ZIKV) is a human teratogen that causes congenital Zika syndrome (CZS). AXL, TLR3, and STAT2 are proteins involved in the ZIKV's entry into cells (AXL) and host's immune response (TLR3 and STAT2). In this study, we evaluated the role of genetic polymorphisms in these three genes as risk factors to CZS, and highlighted which proteins that interact with them could be important for ZIKV infection and teratogenesis.

Materials and methods: We evaluate eighty-eight children exposed to ZIKV during the pregnancy, 40 with CZS and 48 without congenital anomalies. The evaluated polymorphisms in AXL (rs1051008), TLR3 (rs3775291), and STAT2 (rs2066811) were genotyped using TaqMan® Genotyping Assays. A protein-protein interaction network was created in STRING database and analyzed in Cytoscape software.

Results: We did not find any statistical significant association among the polymorphisms and the occurrence of CZS. Through the analyses of the network composed by AXL, TLR3, STAT2 and their interactions targets, we found that EGFR and SRC could be important proteins for the ZIKV infection and its teratogenesis.

Conclusion: In summary, our results demonstrated that the evaluated polymorphisms do not seem to represent risk factors for CZS; however, EGFR and SRC appear to be important proteins that should be investigated in future studies.

Keywords: AXL receptor tyrosine kinase; STAT2 transcription factor; Zika virus infection; congenital abnormalities; disease susceptibility; maternal exposure; toll-like receptor 3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Axl Receptor Tyrosine Kinase
  • Child
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Pregnancy
  • Protein Interaction Maps / genetics
  • Proto-Oncogene Proteins / genetics
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • STAT2 Transcription Factor / genetics
  • STAT2 Transcription Factor / metabolism
  • Teratogenesis*
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / metabolism
  • Zika Virus Infection* / genetics
  • Zika Virus* / physiology

Substances

  • Axl Receptor Tyrosine Kinase
  • Toll-Like Receptor 3
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • ErbB Receptors
  • TLR3 protein, human
  • STAT2 protein, human
  • STAT2 Transcription Factor