Host-Level Susceptibility and IRF1 Expression Influence the Ability of IFN-γ to Inhibit KSHV Infection in B Lymphocytes.
Host-Level Susceptibility and IRF1 Expression Influence the Ability of IFN-γ to Inhibit KSHV Infection in B Lymphocytes.
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DOI：
10.3390/v14102295
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发表时间：
2022-10-19
期刊：
影响因子：
--
通讯作者：
Totonchy J
中科院分区：
文献类型：
--
作者：
Alomari N;Totonchy J
卡波西肉瘤相关疱疹病毒（Kaposi's sarcoma-associated herpesvirus，KSHV）与血管内皮细胞肿瘤、卡波西肉瘤（Kaposi's sarcoma，KS）和淋巴组织增生性疾病、多中心Castleman病（multicentricCastleman's disease，MCD）、原发性渗出性淋巴瘤（primary effusion lymphoma，PEL）和KSHV炎性细胞因子综合征（inflammatory cytokine syndrome，KICS）有关。在大多数KSHV相关疾病中发现了促炎细胞因子的失调。然而，关于宿主微环境在调节KSHV在B细胞中建立中的作用知之甚少。在本研究中，我们证明IFN-γ对KSHV感染具有强烈的抑制作用，但仅在本质上对感染更敏感的扁桃体来源的淋巴细胞样本的子集中，包含较高比例的幼稚B细胞，并显示出IRF1和STAT1-pY701水平升高。IFN-γ在应答样品中的作用与生殖中心B细胞（GCB）频率增加和浆细胞感染减少相关，表明IFN-γ介导的GC中病毒动力学的调节可以抑制KSHV感染的建立。
Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with vascular endothelial cell tumor, Kaposi’s sarcoma (KS) and lymphoproliferative disorder, multicentric Castleman’s disease (MCD), primary effusion lymphoma (PEL) and KSHV inflammatory cytokine syndrome (KICS). Dysregulation of proinflammatory cytokines is found in most KSHV associated diseases. However, little is known about the role of host microenvironment in the regulation of KSHV establishment in B cells. In the present study, we demonstrated that IFN-γ has a strong inhibitory effect on KSHV infection but only in a subset of tonsil-derived lymphocyte samples that are intrinsically more susceptible to infection, contain higher proportions of naïve B cells, and display increased levels of IRF1 and STAT1-pY701. The effect of IFN-γ in responsive samples was associated with increased frequencies of germinal center B cells (GCB) and decreased infection of plasma cells, suggesting that IFN-γ-mediated modulation of viral dynamics in GC can inhibit the establishment of KSHV infection.
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