BAFF receptor deficiency limits gammaherpesvirus infection.
BAFF receptor deficiency limits gammaherpesvirus infection.
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DOI：
10.1128/jvi.03497-13
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发表时间：
2014-04
影响因子：
5.4
通讯作者：
Stevenson PG
中科院分区：
文献类型：
--
作者：
Frederico B;May JS;Efstathiou S;Stevenson PG
γ疱疹病毒（γHV）的淋巴细胞定植是预防癌症的重要目标。然而，它是如何运作的尚不清楚。 Epstein-Barr 病毒在体外驱动自主 B 细胞增殖，但在体内可能更巧妙地利用淋巴生发中心 (GC) 提供的增殖途径。鼠疱疹病毒 4 (MuHV-4) 可实际感染近交小鼠，为进一步了解 γHV 如何在体内定植 B 细胞提供了有用的工具。并非所有 γHV 的行为都必须相同，但 MuHV-4 的常见事件对于宿主定植具有重要意义，因此有可能成为治疗靶点。 MuHV-4 驱动的 B 细胞增殖在数量上取决于 CD4+ T 细胞的帮助。在这里，我们证明它还依赖于 B 细胞激活因子 (BAFF) 受体 (BAFF-R) 提供的 T 细胞独立生存信号。 BAFF-R−/− 小鼠中的 B 细胞可能被感染，但病毒载量仍然较低。这对应于 GC 定植中 BAFF-R 依赖性缺陷。正常的、抗原驱动的 B 细胞反应和病毒感染的 B 细胞增殖之间的密切相似性表明，在体内，γHV 主要诱导受感染的 B 细胞进入正常的 GC 反应，而不是产生大量自主增殖的母细胞。重要性 γHV 通过驱动受感染细胞增殖而导致癌症。 B 细胞是一个特定的目标。因此，我们需要了解病毒驱动的 B 细胞增殖是如何运作的。关于病毒基因是否直接驱动病毒基因或间接协调正常的宿主驱动途径的参与存在争议。在这里，我们表明鼠γHV驱动的B细胞增殖需要BAFF-R。这支持了 γHV 利用宿主增殖途径的观点，并表明干扰 BAFF-R 可以更普遍地减少 γHV 相关的 B 细胞增殖。
Lymphocyte colonization by gammaherpesviruses (γHVs) is an important target for cancer prevention. However, how it works is not clear. Epstein-Barr virus drives autonomous B cell proliferation in vitro but in vivo may more subtly exploit the proliferative pathways provided by lymphoid germinal centers (GCs). Murid herpesvirus 4 (MuHV-4), which realistically infects inbred mice, provides a useful tool with which to understand further how a γHV colonizes B cells in vivo. Not all γHVs necessarily behave the same, but common events can with MuHV-4 be assigned an importance for host colonization and so a potential as therapeutic targets. MuHV-4-driven B cell proliferation depends quantitatively on CD4+ T cell help. Here we show that it also depends on T cell-independent survival signals provided by the B cell-activating factor (BAFF) receptor (BAFF-R). B cells could be infected in BAFF-R−/− mice, but virus loads remained low. This corresponded to a BAFF-R-dependent defect in GC colonization. The close parallels between normal, antigen-driven B cell responses and virus-infected B cell proliferation argue that in vivo, γHVs mostly induce infected B cells into normal GC reactions rather than generating large numbers of autonomously proliferating blasts. IMPORTANCE γHVs cause cancers by driving the proliferation of infected cells. B cells are a particular target. Thus, we need to know how virus-driven B cell proliferation works. Controversy exists as to whether viral genes drive it directly or less directly orchestrate the engagement of normal, host-driven pathways. Here we show that the B cell proliferation driven by a murid γHV requires BAFF-R. This supports the idea that γHVs exploit host proliferation pathways and suggests that interfering with BAFF-R could more generally reduce γHV-associated B cell proliferation.