Medical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
Front Immunol. 2018 Feb 23;9:237. doi: 10.3389/fimmu.2018.00237. eCollection 2018.
The phosphatidylinositol-3-kinase (PI3K)/Akt pathway is important for multiple stages of herpesvirus replication including virus entry, replication, latency, and reactivation. Recently, patients with gain-of-function mutations in the p110δ-catalytic subunit of PI3K or in the p85-regulatory subunit of PI3K have been reported. These patients have constitutively active PI3K with hyperactivation of Akt. They present with lymphoproliferation and often have infections, particularly recurrent respiratory infections and/or severe virus infections. The most frequent virus infections are due to Epstein-Barr virus (EBV) and cytomegalovirus (CMV); patients often present with persistent EBV and/or CMV viremia, EBV lymphoproliferative disease, or CMV lymphadenitis. No patients have been reported with CMV pneumonia, colitis, or retinitis. Other herpesvirus infections have included herpes simplex pneumonia, recurrent zoster, and varicella after vaccination with the varicella vaccine. Additional viral infections have included adenovirus viremia, severe warts, and extensive Molluscum contagiosum virus infection. The increased susceptibility to virus infections in these patients is likely due to a reduced number of long-lived memory CD8 T cells and an increased number of terminally differentiated effector CD8 T cells.
磷脂酰肌醇-3-激酶（PI3K）/Akt 途径对疱疹病毒复制的多个阶段都很重要，包括病毒进入、复制、潜伏和再激活。最近，已经报道了 p110δ-催化亚基或 PI3K 的 p85-调节亚基的 PI3K 获得性功能突变的患者。这些患者具有持续激活的 PI3K 和 Akt 的过度激活。他们表现为淋巴组织增生，并且经常发生感染，特别是复发性呼吸道感染和/或严重病毒感染。最常见的病毒感染是由 Epstein-Barr 病毒（EBV）和巨细胞病毒（CMV）引起的；患者通常表现为持续的 EBV 和/或 CMV 病毒血症、EBV 淋巴组织增生性疾病或 CMV 淋巴结炎。没有报道过 CMV 肺炎、结肠炎或视网膜炎的患者。其他疱疹病毒感染包括单纯疱疹肺炎、复发性带状疱疹和水痘疫苗接种后的水痘。其他病毒感染包括腺病毒病毒血症、严重疣和广泛的传染性软疣病毒感染。这些患者对病毒感染的易感性增加可能是由于长寿命记忆 CD8 T 细胞数量减少和终末分化效应 CD8 T 细胞数量增加所致。
