Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Viruses. 2022 Mar 25;14(4):674. doi: 10.3390/v14040674.
Virus infection of adrenal glands can disrupt secretion of mineralocorticoids, glucocorticoids, and sex hormones from the cortex and catecholamines from the medulla, leading to a constellation of symptoms such as fatigue, dizziness, weight loss, nausea, and muscle and joint pain. Specifically, varicella zoster virus (VZV) can produce bilateral adrenal hemorrhage and adrenal insufficiency during primary infection or following reactivation. However, the mechanisms by which VZV affects the adrenal glands are not well-characterized. Herein, we determined if primary human adrenal cortical cells (HAdCCs) infected with VZV support viral replication and produce a proinflammatory environment. Quantitative PCR showed VZV DNA increasing over time in HAdCCs, yet no cell death was seen at 3 days post-infection by TUNEL staining or Western Blot analysis with PARP and caspase 9 antibodies. Compared to conditioned supernatant from mock-infected cells, supernatant from VZV-infected cells contained significantly elevated IL-6, IL-8, IL-12p70, IL-13, IL-4, and TNF-α. Overall, VZV can productively infect adrenal cortical cells in the absence of cell death, suggesting that these cells may be a potential reservoir for ongoing viral replication and proinflammatory cytokine production, leading to chronic adrenalitis and dysfunction.
病毒感染肾上腺可破坏皮质分泌的盐皮质激素、糖皮质激素和性激素，以及髓质分泌的儿茶酚胺，从而导致一系列症状，如疲劳、头晕、体重减轻、恶心以及肌肉和关节疼痛。具体来说，水痘带状疱疹病毒（VZV）在初次感染或再激活时可导致双侧肾上腺出血和肾上腺功能不全。然而，VZV 影响肾上腺的机制尚未完全阐明。在此，我们确定了是否原发性人肾上腺皮质细胞（HAdCC）感染 VZV 可支持病毒复制并产生促炎环境。定量 PCR 显示 VZV DNA 在 HAdCC 中随时间推移而增加，但在感染后 3 天通过 TUNEL 染色或 PARP 和 caspase 9 抗体的 Western Blot 分析未见细胞死亡。与mock 感染细胞的条件培养基相比，VZV 感染细胞的培养基中含有明显升高的 IL-6、IL-8、IL-12p70、IL-13、IL-4 和 TNF-α。总的来说，VZV 可在没有细胞死亡的情况下有效地感染肾上腺皮质细胞，表明这些细胞可能是持续病毒复制和促炎细胞因子产生的潜在储库，导致慢性肾上腺炎和功能障碍。
