Wu Zeguang, Sinzger Christian, Reichel Johanna Julia, Just Marlies, Mertens Thomas
Institute of Virology, Ulm University Medical Center, Ulm, Germany.
Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
J Virol. 2015 Mar;89(5):2906-17. doi: 10.1128/JVI.03489-14. Epub 2014 Dec 24.
Human cytomegalovirus (HCMV) transmission within the host is important for the pathogenesis of HCMV diseases. Natural killer (NK) cells are well known to provide a first line of host defense against virus infections. However, the role of NK cells in the control of HCMV transmission is still unknown. Here, we provide the first experimental evidence that NK cells can efficiently control HCMV transmission in different cell types. NK cells engage different mechanisms to control the HCMV transmission both via soluble factors and by cell contact. NK cell-produced interferon gamma (IFN-γ) suppresses HCMV production and induces resistance of bystander cells to HCMV infection. The UL16 viral gene contributes to an immune evasion from the NK cell-mediated control of HCMV transmission. Furthermore, the efficacy of the antibody-dependent NK cell-mediated control of HCMV transmission is dependent on a CD16-158V/F polymorphism. Our findings indicate that NK cells may have a clinical relevance in HCMV infection and highlight the need to consider potential therapeutic strategies based on the manipulation of NK cells.
Human cytomegalovirus (HCMV) infects 40% to 100% of the human population worldwide. After primary infection, mainly in childhood, the virus establishes a lifelong persistence with possible reactivations. Most infections remain asymptomatic; however, HCMV represents a major health problem since it is the most frequent cause of infection-induced birth defects and is responsible for high morbidity and mortality in immunocompromised patients. The immune system normally controls the infection by antibodies and immune effector cells. One type of effector cells are the natural killer (NK) cells, which provide a rapid response to virus-infected cells. NK cells participate in viral clearance by inducing the death of infected cells. NK cells also secrete antiviral cytokines as a consequence of the interaction with an infected cell. In this study, we investigated the mechanisms by which NK cells control HCMV transmission, from the perspectives of immune surveillance and immune evasion.
人巨细胞病毒（HCMV）在宿主体内的传播对于HCMV疾病的发病机制很重要。自然杀伤（NK）细胞是众所周知的提供宿主抵御病毒感染的第一道防线。然而，NK细胞在控制HCMV传播中的作用仍然未知。在此，我们提供了首个实验证据，表明NK细胞可以有效控制不同细胞类型中的HCMV传播。NK细胞通过可溶性因子和细胞接触参与不同机制来控制HCMV传播。NK细胞产生的干扰素γ（IFN-γ）抑制HCMV产生并诱导旁观者细胞对HCMV感染产生抗性。UL16病毒基因有助于HCMV逃避NK细胞介导的传播控制。此外，抗体依赖性NK细胞介导的HCMV传播控制的功效取决于CD16-158V/F多态性。我们的发现表明NK细胞可能在HCMV感染中具有临床相关性，并强调需要考虑基于操纵NK细胞的潜在治疗策略。
人巨细胞病毒（HCMV）感染全球40%至100%的人群。初次感染后，主要在儿童期，病毒建立终身潜伏并可能重新激活。大多数感染无症状；然而，HCMV是一个主要的健康问题，因为它是感染引起的出生缺陷最常见的原因，并且在免疫功能低下的患者中导致高发病率和死亡率。免疫系统通常通过抗体和免疫效应细胞控制感染。一种效应细胞是自然杀伤（NK）细胞，它对病毒感染细胞提供快速反应。NK细胞通过诱导感染细胞死亡参与病毒清除。NK细胞与感染细胞相互作用还会分泌抗病毒细胞因子。在本研究中，我们从免疫监视和免疫逃避的角度研究了NK细胞控制HCMV传播的机制。
