Tisoncik-Go Jennifer, Lewis Thomas B, Whitmore Leanne S, Voss Kathleen, Niemeyer Skyler, Dai Jin, Kim Paul, Hubbell Kai, Iwayama Naoto, Ahrens Chul, Wangari Solomon, Murnane Robert, Edlefsen Paul T, Guerriero Kathryn A, Gale Michael, Fuller Deborah H, O'Connor Megan A
Washington National Primate Research Center, University of Washington, Seattle, WA, United States.
Department of Immunology, University of Washington, Seattle, WA, United States.
Front Immunol. 2025 Mar 4;16:1535807. doi: 10.3389/fimmu.2025.1535807. eCollection 2025.
Mosquito-borne flaviviruses, including dengue (DENV) and Zika (ZIKV) viruses, have caused widespread epidemics in areas with high HIV prevalence, partly due to the expanded geographic range of arthropod vectors. Despite the occurrence of large flavivirus outbreaks in areas with high HIV prevalence, little is known about the effects of flavivirus infection in people living with HIV (PLWH). Here, we use a pigtail macaque model of HIV/AIDS to investigate the impact of simian immunodeficiency virus (SIV)-induced immunosuppression on ZIKV replication and pathogenesis. During acute SIV infection, peripheral ZIKV cellular targets expanded and innate immune activation increased. , peripheral blood mononuclear cells (PBMC) from SIV infected pigtail macaques were less permissive to ZIKV infection. , ZIKV viremia was delayed and ZIKV was more persistent in the gastrointestinal tissues of SIV-ZIKV co-infected animals. This persistence was associated with changes in innate cellular (monocytes, neutrophils) recruitment to the blood and tissues, reduced anti-ZIKV immunity, and sustained expression of peripheral inflammatory and innate immune genes. Collectively, these findings uniquely suggest that untreated SIV infection may promote inflammatory cellular innate responses and create a state of persistent immune activation that contributes to prolonged ZIKV viremia and persistence in the gastrointestinal tract. Furthermore, these results suggest that PLWH and other immunocompromised individuals could be at higher risk for prolonged ZIKV infection, potentially extending the window of ZIKV transmission. These insights highlight the importance of including PLWH in strategies for deploying vaccines and treatments against ZIKV.
包括登革热病毒（DENV）和寨卡病毒（ZIKV）在内的蚊媒黄病毒，已在艾滋病毒高流行地区引发了广泛的疫情，部分原因是节肢动物媒介的地理分布范围扩大。尽管在艾滋病毒高流行地区发生了大规模的黄病毒疫情，但对于黄病毒感染对艾滋病毒感染者（PLWH）的影响却知之甚少。在此，我们使用艾滋病毒/艾滋病的猪尾猕猴模型，来研究猿猴免疫缺陷病毒（SIV）诱导的免疫抑制对寨卡病毒复制和发病机制的影响。在急性SIV感染期间，外周寨卡病毒细胞靶点扩大，固有免疫激活增加。然而，来自感染SIV的猪尾猕猴的外周血单核细胞（PBMC）对寨卡病毒感染的敏感性较低。此外，寨卡病毒血症出现延迟，且寨卡病毒在SIV-ZIKV共感染动物的胃肠道组织中持续存在的时间更长。这种持续性与血液和组织中固有细胞（单核细胞、中性粒细胞）募集的变化、抗寨卡病毒免疫力降低以及外周炎症和固有免疫基因的持续表达有关。总体而言，这些发现独特地表明，未经治疗的SIV感染可能促进炎症性细胞固有反应，并产生一种持续免疫激活状态，这有助于寨卡病毒血症的延长以及在胃肠道中的持续存在。此外，这些结果表明，艾滋病毒感染者和其他免疫功能低下的个体可能面临更长时间寨卡病毒感染的更高风险，这可能会延长寨卡病毒的传播窗口期。这些见解凸显了将艾滋病毒感染者纳入寨卡病毒疫苗和治疗策略的重要性。
