Moraes Amarilis Giaretta de, Ayo Christiane Maria, Elpídio Laise Nayana Sala, Souza Victor Hugo de, Yamanaka Aléia Harumi Uchibaba, Nogueira Maurício Lacerda, Passos Saulo Duarte, Brandão Cinara Cássia, Mattos Luiz Carlos de, Amaral Greicy Cezar do, Neto Quirino Alves de Lima, Visentainer Jeane Eliete Laguila
Post Graduation Program in Biosciences and Physiopathology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá 87020-270, PR, Brazil.
Laboratory of Immunogenetics, Department of Basic Health Sciences, State University of Maringá, Maringá 87020-270, PR, Brazil.
Curr Issues Mol Biol. 2022 Jun 27;44(7):2783-2793. doi: 10.3390/cimb44070191.
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 , and 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 / ( = 0.03, = 0.06, OR = 12.4; = 0.008, = 0.016, OR = 16.4) and / ( = 0.01, = 0.02, OR = 19.2; = 0.008, = 0.016, OR = 16.4). ( = 0.04, = 0.52, OR = 4.30) was also a susceptibility factor. / ( = 0.02, = 0.08, OR = 0.07), / ( = 0.01, = 0.04, OR = 0.04) and / ( = 0.04, = 0.52, OR = 0.14) were suggested as protective factors against vertical transmission. The current study suggests that polymorphic sites in the and genes might be associated with mother-to-child ZIKV transmission while might be associated with protection against ZIKV transmission in the womb in a population from the south and southeast of Brazil.
在2015 - 2016年疫情期间,巴西是美洲地区寨卡病毒(ZIKV)感染率最高的国家。29%的ZIKV检测呈阳性的孕妇超声检查显示胎儿有异常。人类白细胞抗原G(HLA - G)通过与抑制性受体LILRB1和LILRB2结合发挥免疫调节作用,从而防止母胎排斥和病原体垂直传播。HLA - G与其一种受体的结合可调节先天性免疫和适应性免疫。然而,在病毒感染时,这些分子可能作为致病介质,使妊娠环境从抗炎状态转变为促炎表型。基因突变可能与表型变化有关。本研究旨在探讨HLA - G基因的rs1063320、rs1063321和rs1063323多态性位点在母胎ZIKV传播中的可能作用。通过直接测序检测多态性。采用Mid - P精确检验或Yates校正比较ZIKV非传播和传播母婴对、ZIKV传播和非传播母亲以及ZIKV感染和未感染儿童中每个分析SNP的等位基因和/或基因型频率差异。对于rs1063320/rs1063321(P = 0.03,Pc = 0.06,OR = 12.4;P = 0.008,Pc = 0.016,OR = 16.4)和rs1063321/rs1063323(P = 0.01,Pc = 0.02,OR = 19.2;P = 0.008,Pc = 0.016,OR = 16.4),提示ZIKV垂直传播存在显著易感性。rs1063323(P = 0.04,Pc = 0.52,OR = 4.30)也是一个易感因素。rs1063320/rs1063321(P = 0.02,Pc = 0.08,OR = 0.07)、rs1063321/rs1063323(P = 0.01,Pc = 0.04,OR = 0.04)和rs1063323/rs1063320(P = 0.04,Pc = 0.52,OR = 0.14)被认为是防止垂直传播的保护因素。当前研究表明,在巴西南部和东南部人群中,HLA - G基因的rs1063320和rs1063321多态性位点可能与母婴ZIKV传播有关,而rs1063323可能与子宫内预防ZIKV传播有关。