IMPORTANCE OF INTERFERONS IN RECOVERY FROM MOUSEPOX
IMPORTANCE OF INTERFERONS IN RECOVERY FROM MOUSEPOX
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DOI：
10.1128/jvi.67.7.4214-4226.1993
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发表时间：
1993-07-01
影响因子：
5.4
通讯作者：
BULLER, RML
中科院分区：
文献类型：
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作者：
KARUPIAH, G;FREDRICKSON, TN;BULLER, RML
研究表明，γ 干扰素对于 C57BL/6 小鼠的鼠痘恢复至关重要。对足垫感染节肢动物病毒的小鼠进行抗γ干扰素治疗，导致病毒在脾、肺、卵巢，尤其是肝脏中的扩散增强和有效复制。所有接受治疗的感染小鼠平均在 7 天内死亡，比接受类似感染的严重联合免疫缺陷小鼠早 2.5 天。另一方面，α干扰素似乎在控制所检查组织中的病毒复制方面没有主要作用，而β干扰素对于肝脏和卵巢中的病毒清除很重要，但对脾脏中的病毒清除则不然。抗α、β干扰素或抗β干扰素抗体疗法仅导致25%的死亡率。受感染的对照小鼠存活下来，但在感染部位（足垫）显示出短肢病毒的持续存在，并且该病毒在脾脏、肝脏、肺和卵巢以及引流腘淋巴结的纤维网状细胞中短暂存在，但不存在淋巴样细胞。 γ干扰素而非α和/或β干扰素的消耗导致脾脏T（尤其是γ-TCR+）、B和Mac-1+细胞的数量显着减少，尽管与对照值相比，脾脏中Mac-1+细胞的比例增加。 α、β或γ干扰素的消耗不会严重影响病毒特异性细胞毒性T淋巴细胞反应或自然杀伤细胞溶细胞活性的产生。这项研究使用了自然病毒疾病模型，强调了γ干扰素在感染所有阶段和所有测试组织中病毒清除的至关重要性，但原发感染部位除外，原发感染部位的病毒清除似乎被延迟。
Gamma interferon is shown to be critical in recovery of C57BL/6 mice from mousepox. Anti-gamma interferon treatment of mice infected in the footpad with ectromelia virus resulted in enhanced spread to and efficient virus replication in the spleen, lungs, ovaries, and, especially, liver. All treated, infected mice died within a mean of 7 days, 2.5 days earlier than mice with severe combined immunodeficiency that were given a comparable infection. On the other hand, alpha interferon appeared not to have a major role in controlling virus replication in tissues examined, and beta interferon was important for virus clearance in the liver and ovaries but not the spleen. Either anti-alpha, beta interferon or anti-beta interferon antibody therapy resulted in only 25% mortality. Infected control mice survived but showed persistence of ectromelia virus at the site of infection (the footpad) and transient presence of the virus in the spleen, liver, lungs, and ovaries and in the fibroreticular but not lymphoid cells of the draining popliteal lymph node. Depletion of gamma interferon but not alpha and/or beta interferon resulted in a significant reduction in the numbers of splenic T (especially gammdelta-TCR+), B, and Mac-1+ cells, although the proportion of Mac-l+ cells in the spleen increased compared with control values. Depletion of alpha, beta, or gamma interferons did not severely affect the generation of virus-specific cytotoxic T-lymphocyte responses or natural killer cell cytolytic activity. This study, in which a natural virus disease model was used, underscores the crucial importance of gamma interferon in virus clearance at all stages of infection and in all tissues tested except the primary site of infection, where virus clearance appears to be delayed.