Cervical and systemic innate immunity predictors of HIV risk linked to genital herpes acquisition and time from HSV-2 seroconversion.
Cervical and systemic innate immunity predictors of HIV risk linked to genital herpes acquisition and time from HSV-2 seroconversion.
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DOI：
10.1136/sextrans-2022-055458
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发表时间：
2023-08
影响因子：
3.6
通讯作者：
中科院分区：
文献类型：
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作者：
探讨先天免疫预测HIV-1感染的生物标志物HSV-2的风险和生物学基础的流行病学确定的HIV-1易感性HSV-2感染的妇女。我们分析了1019名女性在HSV-2获得前后HIV-1阴性访视的纵向样本。我们测量了先前与HIV-1风险相关的炎症和免疫激活的宫颈和血清生物标志物。对蛋白水平进行Box-Cox转换，并基于所有HSV-2阴性访视的前四分位数或低于/高于中位水平计算HSV-2采集的OR。双变量分析通过感染前的生物标志物水平确定HSV-2获得的可能性。线性混合效应模型评价生物标志物是否因HSV-2状态而不同，HSV-2状态定义为阴性、偶发或已确立感染，已确立感染截止时间从6个月开始。在宫颈隔室中，HIV-1风险的两种生物标志物（低SLPI和高BD-2）也预测HSV-2的获得。此外，HSV-2感染与IL-1β、IL-6、IL-8、MIP-3α、ICAM-1和VEGF相关，低于中位数水平。HSV-2感染的全身免疫预测因子是高sCD 14和IL-6，当sCD 14和IL-6同时升高时，比值最高（OR=2.23，1.49-3.35）。HSV-2感染风险的伴随全身和粘膜预测因子包括（1）血清前四分位sCD 14与宫颈低SLPI、VEGF和ICAM-1或高BD-2;（2）血清高IL-6与宫颈低VEGF和ICAM-1、SLPI、IL-1β和IL-6;和（3）血清低C反应蛋白与宫颈高BD-2（唯一的组合也预测HIV-1感染）。与HSV-2阴性访视相比，大多数宫颈生物标志物在HSV-2获得后降低，与确定的感染相比，与大量受抑制的宫颈生物标志物和较低的血清IL-6水平相关的偶发感染。全身免疫炎症和宫颈免疫抑制状态的组合预测HSV-2的收购。在HSV-2感染期间持续抑制先天免疫可能增加HIV-1易感性。
To examine innate immunity predictors of HIV-1 acquisition as biomarkers of HSV-2 risk and biological basis for epidemiologically established HIV-1 predisposition in HSV-2 infected women. We analysed longitudinal samples from HIV-1 negative visits of 1019 women before and after HSV-2 acquisition. We measured cervical and serum biomarkers of inflammation and immune activation previously linked to HIV-1 risk. Protein levels were Box-Cox transformed and ORs for HSV-2 acquisition were calculated based on top quartile or below/above median levels for all HSV-2 negative visits. Bivariate analysis determined the likelihood of HSV-2 acquisition by biomarker levels preceding infection. Linear mixed-effects models evaluated if biomarkers differed by HSV-2 status defined as negative, incident or established infections with an established infection cut-off starting at 6 months. In the cervical compartment, two biomarkers of HIV-1 risk (low SLPI and high BD-2) also predicted HSV-2 acquisition. In addition, HSV-2 acquisition was associated with IL-1β, IL-6, IL-8, MIP-3α, ICAM-1 and VEGF when below median levels. Systemic immunity predictors of HSV-2 acquisition were high sCD14 and IL-6, with highest odds when concomitantly increased (OR=2.23, 1.49–3.35). Concomitant systemic and mucosal predictors of HSV-2 acquisition risk included (1) serum top quartile sCD14 with cervical low SLPI, VEGF and ICAM-1, or high BD-2; (2) serum high IL-6 with cervical low VEGF and ICAM-1, SLPI, IL-1β and IL-6; and (3) serum low C reactive protein with cervical high BD-2 (the only combination also predictive of HIV-1 acquisition). Most cervical biomarkers were decreased after HSV-2 acquisition compared with the HSV-2 negative visits, with incident infections associated with a larger number of suppressed cervical biomarkers and lower serum IL-6 levels compared with established infections. A combination of systemic immunoinflammatory and cervical immunosuppressed states predicts HSV-2 acquisition. A persistently suppressed innate immunity during incident HSV-2 infection may add to the increased HIV-1 susceptibility.
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影响因子：
15.9
作者：
MCNEELY, TB;DEALY, M;WAHL, SM
通讯作者：
WAHL, SM
影响因子：
15.8
作者：
Torrone EA;Morrison CS;Chen PL;Kwok C;Francis SC;Hayes RJ;Looker KJ;McCormack S;McGrath N;van de Wijgert JHHM;Watson-Jones D;Low N;Gottlieb SL;STIMA Working Group
通讯作者：
STIMA Working Group
影响因子：
3.7
作者：
Fichorova, Raina N.;Morrison, Charles S.;Doncel, Gustavo F.
通讯作者：
Doncel, Gustavo F.
DOI：
10.1073/pnas.0901983106
发表时间：
2009-04-21
影响因子：
11.1
作者：
Redd, Andrew D.;Dabitao, Djeneba;Quinn, Thomas C.
通讯作者：
Quinn, Thomas C.
影响因子：
5.4
作者：
Wilson, Sarah S.;Wiens, Mayim E.;Smith, Jason G.
通讯作者：
Smith, Jason G.