HLA-G, LILRB1 and LILRB2 Variants in Zika Virus Transmission from Mother to Child in a Population from South and Southeast of Brazil

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de Moraes, Amarilis Giaretta ; Ayo, Christiane Maria ; Sala Elpidio, Laise Nayana ; de Souza, Victor Hugo ; Uchibaba Yamanaka, Aleia Harumi ; Nogueira, Mauricio Lacerda ; Passos, Saulo Duarte ; Brandao, Cinara Cassia ; de Mattos, Luiz Carlos ; do Amaral, Greicy Cezar ; de Lima Neto, Quirino Alves ; Laguila Visentainer, Jeane Eliete

• Document type: Journal article
• Source: CURRENT ISSUES IN MOLECULAR BIOLOGY; v. 44, n. 7, p. 11-pg., 2022-07-01.

Abstract

During the 2015-2016 epidemic, Brazil was the country with the highest rate of Zika virus (ZIKV) infection in the Americas. Twenty-nine percent of pregnant women positive for ZIKV exhibited ultrasound scans with fetus anomalies. Human leukocyte antigen-G (HLA-G) exerts immunoregulatory effects by binding to inhibitory receptors, namely LILRB1 and LILRB2, thus preventing mother-fetus rejection and vertical pathogen transmission. The binding of HLA-G to one of its receptors modulates both innate and adaptive immunity. However, in a viral infection, these molecules may behave as pathogenic mediators shifting the pregnancy environment from an anti-inflammatory profile to a pro-inflammatory phenotype. Genetic mutations might be associated with the change in phenotype. This study aimed to explore the possible role of polymorphic sites in HLA-G, LILRB1 and LILRB2 in mother-fetus ZIKV transmission. Polymorphisms were detected by direct sequencing. Differences in allele and/or genotype frequencies for each SNP analyzed among ZIKV non-transmitting and transmitting mother-child pairs, among ZIKV-transmitting and non-transmitting mothers and between ZIKV-infected and non-infected children were compared by Mid-P exact test or Yates' correction. Significant susceptibility of ZIKV vertical transmission is suggested in ZIKV-transmitting and non-transmitting mothers and ZIKV-infected and non-infected children for LILRB1_rs1061684 T/T (p = 0.03, Pc = 0.06, OR = 12.4; p = 0.008, Pc = 0.016, OR = 16.4) and LILRB1_rs16985478 A/A (p = 0.01, Pc = 0.02, OR = 19.2; p = 0.008, Pc = 0.016, OR = 16.4). HLA-G_rs1710 (p = 0.04, Pc = 0.52, OR = 4.30) was also a susceptibility factor. LILRB2_rs386056 G/A (p = 0.02, Pc = 0.08, OR = 0.07), LILRB2_rs7247451 G/G (p = 0.01, Pc = 0.04, OR = 0.04) and HLAG_rs9380142 T/T (p = 0.04, Pc = 0.52, OR = 0.14) were suggested as protective factors against vertical transmission. The current study suggests that polymorphic sites in the LILRB1 and HLA-G genes might be associated with mother-to-child ZIKV transmission while LILRB2 might be associated with protection against ZIKV transmission in the womb in a population from the south and southeast of Brazil. (AU)

• FAPESP's process: 16/05115-9 - Innate and adaptive immune response genes in the Zika virus infection
• Grantee: Luiz Carlos de Mattos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/08578-0 - Vertical infection by the virus Zika and its impact on the mother-child area
• Grantee: Saulo Duarte Passos
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/15021-1 - Clinical-epidemiological study of a cohort of Zika infected pregnant women in São José do Rio Preto, SP
• Grantee: Maurício Lacerda Nogueira
• Support Opportunities: Research Grants - Research in Public Policies for the National Health Care System (PP-SUS)