Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Oct 1;115(16):1500-1512.
doi: 10.1002/bdr2.2232. Epub 2023 Aug 1.

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

Julia A Gomes  1   2 , Eduarda Sgarioni  2   3 , Juliano A Boquett  1   4   5 , Thayne W Kowalski  1   2   3   6 , Lucas R Fraga  2   6   7   8 , Ana Cláudia P Terças-Trettel  9   10 , Juliana H da Silva  11 , Bethânia F R Ribeiro  12 , Marcial F Galera  13   14 , Thalita M de Oliveira  14 , Maria Denise F Carvalho de Andrade  15   16   17   18 , Isabella F Carvalho  16 , Lavínia Schüler-Faccini  1   3   4   6 , Fernanda S L Vianna  1   2   3   6   7
Affiliations

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

Julia A Gomes et al. Birth Defects Res. .

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.

PubMed Disclaimer

References

REFERENCES

    1. Ackerman, S. (1992). The development and shaping of the brain. In Discovering the Brain. National Academies Press (US) Chapter 6. Available from: https://www.ncbi.nlm.nih.gov/books/NBK234146/
    1. Agrelli, A., de Moura, R. R., Crovella, S., & Brandão, L. A. C. (2019). ZIKA virus entry mechanisms in human cells. Infection, Genetics and Evolution, 69, 22-29.
    1. Aguiar, R. S., Pohl, F., Morais, G. L., Nogueira, F. C. S., Carvalho, J. B., Guida, L., Arge, L. W. P., Melo, A., Moreira, M. E. L., Cunha, D. P., Gomes, L., Portari, E. A., Velasquez, E., Melani, R. D., Pezzuto, P., de Castro, F. L., Geddes, V. E. V., Gerber, A. L., Azevedo, G. S., … Nakaya, H. I. (2020). Molecular alterations in the extracellular matrix in the brains of newborns with congenital Zika syndrome. Science Signaling, 13, eaay6736.
    1. Azamor, T., Cunha, D. P., da Silva, A. M. V., Bezerra, O. C. L., Ribeiro-Alves, M., Calvo, T. L., Kehdy, F. S. G., Manta, F. S. N., Pinto, T. G. T., Ferreira, L. P., Portari, E. A., Guida, L. D. C., Gomes, L., Moreira, M. E. L., de Carvalho, E. F., Cardoso, C. C., Muller, M., Ano Bom, A. P. D., Neves, P. C. D. C., … Moraes, M. O. (2021). Congenital Zika syndrome is associated with interferon alfa receptor 1. Frontiers in Immunology, 12, 764746.
    1. Barik, S. (2022). Mechanisms of viral degradation of cellular signal transducer and activator of transcription 2. International Journal of Molecular Sciences, 23(1), 489.

Publication types

MeSH terms

LinkOut - more resources