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

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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.
Funding Information
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
  • Hospital de Clínicas de Porto Alegre
  • Instituto Nacional de Genética Médica Populacional
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
  • Instituto Nacional de Genética Médica Populacional
  • Hospital de Clínicas de Porto Alegre
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico

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