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Innate and adaptive immune response genes in the Zika Virus infection

Grant number: 16/05115-9
Support type:Regular Research Grants
Duration: September 01, 2016 - August 31, 2018
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Luiz Carlos de Mattos
Grantee:Luiz Carlos de Mattos
Home Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil
Assoc. researchers:Cinara de Cássia Brandão de Mattos
Associated scholarship(s):17/26833-0 - Innate and adaptive immune response genes in the Zika virus infection, BP.TT

Abstract

The growing epidemic by Zika virus in Brazil is one of the most important challenges for contemporary Brazilian science not only for cases of microcephaly potentially associated with this virus as well as for the investigation of many aspects of the immune responses (innate and adaptive) among infected individuals, symptomatic and asymptomatic. The main objective is to test the hypothesis that the genes of the innate immune response (KIR, MICA, TLR) and adaptive (HLA) are associated with Zika virus infection and the microcephaly potentially related to this virus. Its specific objectives are: 1 - Select two groups of patients with Zika virus infection constituted as follows: Group 1 - pregnant women with infection by Zika virus and symptomatic; Group 2 - pregnant women with infection by Zika virus and asymptomatic; 2. To confirm the infection by Zika virus infection by molecular methods in both groups; 3. Identifying the HLA class I genes (HLA-A, HLA-B and HLA-C) and II (HLA-DRB1, HLA-DQB1), KIRs and their ligands, MICA, TLR3 and TLR7 genes in both groups ; 4. Verify if these genes are associated with the presence or absence of symptoms in both groups; 5. Check if one or more of these genes are associated with microcephaly potentially related to infection by Zika virus. Pregnant women from São José do Rio Preto and region receiving medical attention at Children's Hospital and Maternity will be enrolled. In addition to epidemiological data, samples of blood and urine will be collected for laboratory investigation of Zika virus infection. Amplification of Viral RNA by real-time PCR (qPCR) with primers and probes specific to the regions of the structural membrane protein (M) and envelope (E) genes of the Flavivirus as well as the RT-PCR method for the detection of Zika virus with specific primers for nonstructural protein gene 5 (NS5) will be used. Genomic DNA will be used for genotyping of KIR genes, MICA and HLA by PCR-SSOP method. The MICA-129 functional polymorphism (A>G, rs1051792) will be analyzed by the method PCR and Nested and the TLR3 rs3775291 polymorphism rs179008 TLR7 and will be analyzed by allelic discrimination with the qPCR method. The gene frequencies of KIR and MICA-129 rs1051792 alleles, TLR3 rs3775291 and rs179008 TLR7 be obtained by direct counting. The alleles and haplotypes of HLA class I and II will be analyzed using the Arlequin program, version 3.1. Comparisons of KIR gene frequencies and their HLA ligands and the MICA gene polymorphism will be performed using the chi-square test with Yates correction or Fisher's exact test (p<0.05). The results to be achieved will know if the HLA genes, KIR, MICA and TLR are immunogenetic factors that influence the immune response and infection Zika virus. We can understand the importance of immunogenetic changes to the guidance of enlightenment programs, education, prevention, treatment of infection and disease caused by Zika virus and development of vaccines and new therapeutic drugs.Key-words: Zika virus, Microcephaly, HLA, MICA, KIR, Toll-Like receptors (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
NOGUEIRA, M. L.; NERY JUNIOR, N. R. R.; ESTOFOLETE, C. F.; BERNARDES TERZIAN, A. C.; GUIMARAES, G. F.; ZINI, N.; ALVES DA SILVA, R.; DUTRA SILVA, G. C.; JUNQUEIRA FRANCO, L. C.; RAHAL, P.; BITTAR, C.; CARNEIRO, B.; VASCONCELOS, P. F. C.; FREITAS HENRIQUES, D.; BARBOSA, D. M. U.; LOPES ROMBOLA, P.; DE GRANDE, L.; NEGRI REIS, A. F.; PALOMARES, S. A.; WAKAI CATELAN, M.; CRUZ, L. E. A. A.; NECCHI, S. H.; MENDONCA, R. C. V.; PENHA DOS SANTOS, I. N.; ALAVARSE CARON, S. B.; COSTA, F.; BOZZA, F. A.; SOARES DE SOUZA, A.; BRANDAO DE MATTOS, C. C.; DE MATTOS, L. C.; VASILAKIS, N.; OLIANI, A. H.; VAZ OLIANI, D. C. M.; KO, A. I. Adverse birth outcomes associated with Zika virus exposure during pregnancy in Sao Jose do Rio Preto, Brazil. Clinical Microbiology and Infection, v. 24, n. 6, p. 646-652, JUN 2018. Web of Science Citations: 10.
DE SOUZA, ANTONIO SOARES; DIAS, CRISTIANE MORAES; BRAOJOS BRAGA, FERNANDA DEL CAMPO; BERNARDES TERZIAN, ANA CAROLINA; ESTOFOLETE, CASSIA FERNANDA; OLIANI, ANTONIO HELIO; OLIVEIRA, GUSTAVO HENRIQUE; BRANDAO DE MATTOS, CINARA CASSIA; DE MATTOS, LUIZ CARLOS; NOGUEIRA, MAURICIO LACERDA; MOS VAZ-OLIANI, DENISE CRISTINA. Fetal Infection by Zika Virus in the Third Trimester: Report of 2 Cases. Clinical Infectious Diseases, v. 63, n. 12, p. 1622-1625, DEC 15 2016. Web of Science Citations: 33.

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