KSHV infection drives poorly cytotoxic CD56-negative natural killer cell differentiation in vivo upon KSHV/EBV dual infection.
KSHV infection drives poorly cytotoxic CD56-negative natural killer cell differentiation in vivo upon KSHV/EBV dual infection.
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DOI：
10.1016/j.celrep.2021.109056
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发表时间：
2021-05-04
期刊：
影响因子：
8.8
通讯作者：
Muenz, Christian
中科院分区：
文献类型：
--
作者：
Caduff, Nicole;McHugh, Donal;Rieble, Lisa;Forconi, Catherine S.;Ong'echa, John M.;Oluoch, Peter O.;Raykova, Ana;Murer, Anita;Boeni, Michelle;Zuppiger, Lara;Schulz, Thomas F.;Blackbourn, David J.;Chijioke, Obinna;Moormann, Ann M.;Muenz, Christian
疱疹病毒感染塑造了人类自然杀伤 (NK) 细胞区室。 Epstein-Barr 病毒 (EBV) 会扩增未成熟的 NKG2A+ NK 细胞，而人巨细胞病毒 (CMV) 则会促进适应性 NKG2C+ NK 细胞的积累。卡波西肉瘤相关疱疹病毒 (KSHV) 是 EBV 的近亲，两者都与淋巴瘤相关，包括原发性渗出性淋巴瘤 (PEL)，几乎总是携带这两种病毒。在这项研究中，KSHV 双重感染具有重建的人类免疫系统成分的小鼠导致 CD56−CD16+CD38+CXCR6+ NK 细胞的积累。 CD56−CD16+ NK 细胞在 KSHV 血清阳性肯尼亚儿童中也更常见。该 NK 细胞亚群对 NK 细胞敏感和抗体调理靶标的细胞毒性很弱。因此，NK 细胞耗竭不会显着改变人源化小鼠中的 KSHV 感染。这些数据表明，KSHV 可能通过驱动 CD56−CD16+ NK 细胞分化来逃避 NK 细胞介导的免疫控制。卡达夫等人。利用人源化小鼠模型来表征人类肿瘤病毒 KSHV 和 EBV 双重感染后 NK 细胞的反应。他们描述了体内 KSHV 病毒血症导致功能失调的 CD56−CD16+ NK 细胞增加，并且该亚群在 KSHV 血清阳性儿童中积累。
Herpesvirus infections shape the human natural killer (NK) cell compartment. While Epstein-Barr virus (EBV) expands immature NKG2A+ NK cells, human cytomegalovirus (CMV) drives accumulation of adaptive NKG2C+ NK cells. Kaposi sarcoma-associated herpesvirus (KSHV) is a close relative of EBV, and both are associated with lymphomas, including primary effusion lymphoma (PEL), which nearly always harbors both viruses. In this study, KSHV dual infection of mice with reconstituted human immune system components leads to the accumulation of CD56−CD16+CD38+CXCR6+ NK cells. CD56−CD16+ NK cells were also more frequently found in KSHV-seropositive Kenyan children. This NK cell subset is poorly cytotoxic against otherwise-NK-cell-susceptible and antibody-opsonized targets. Accordingly, NK cell depletion does not significantly alter KSHV infection in humanized mice. These data suggest that KSHV might escape NK-cell-mediated immune control by driving CD56−CD16+ NK cell differentiation. Caduff et al. utilize a humanized mouse model to characterize NK cell responses upon dual infection with the human tumor viruses KSHV and EBV. They describe an increase of dysfunctional CD56−CD16+ NK cells with KSHV viremia in vivo and an accumulation of this subset in KSHV-seropositive children.
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