Role of virus replication in a murine model of AIDS-associated interstitial pneumonitis.
Role of virus replication in a murine model of AIDS-associated interstitial pneumonitis.
复制标题
病毒复制在艾滋病相关间质性肺炎小鼠模型中的作用。
DOI：
10.1080/019021499269972
复制
发表时间：
1999
影响因子：
1.7
通讯作者：
Cohen,DA
中科院分区：
文献类型：
--
作者：
Fitzpatrick,EA;Avdiushko,M;Kaplan,AM;Cohen,DA
HIV感染的主要并发症之一是发生间质性肺炎（IP）。IP的特征是肺部淋巴细胞浸润，在某些情况下可能导致呼吸衰竭。IP的病因尚不清楚，但可能是肺部发生抗病毒或自身免疫反应的结果。为了确定病毒复制在IP发展中的作用，在逆转录病毒相关IP的小鼠模型中评价了AZT抑制肺部炎症发展的能力。用LP-BM 5逆转录病毒感染小鼠，其诱导小鼠AIDS。感染小鼠在感染后4周出现IP，其特征为活化的T细胞、B细胞和巨噬细胞浸润肺。病毒感染后2周可在这些小鼠的肺中检测到，并在整个疾病过程中持续存在。为了确定病毒载量的减少是否影响疾病的进程，感染小鼠在感染后不同时期接受AZT治疗，并分析IP的发展。与未治疗的感染小鼠相比，AZT治疗导致感染小鼠肺中病毒RNA的治疗时间依赖性减少。肺部病毒负荷的降低与IP严重程度的降低以及促炎细胞因子白细胞介素（IL）-1 β和干扰素（IFN）-γ的产生减少相关。这些结果表明，持续病毒复制在肺有助于IP的发病机制。
One of the major complications of HIV infection is the development of interstitial pneumonitis (IP). IP is characterized by lymphocytic infiltration of the lung and may lead to respiratory failure in some cases. The etiology of IP is unknown although it is likely the result of an antiviral or autoimmune response occurring in the lung. To determine the role of viral replication in the development of IP, AZT was evaluated for the ability to inhibit development of lung inflammation in a murine model of retrovirus-associated IP. Mice were infected with LP-BM5 retrovirus, which induces murine AIDS. Infected mice develop IP by 4 weeks postinfection characterized by infiltration of the lung with activated T cells, B cells, and macrophages. Virus could be detected in the lungs of these mice by 2 weeks postinfection and persisted throughout the course of disease. To determine if reduction in viral load affected the disease process, infected mice were treated with AZT for varying periods postinfection and analyzed for the development of IP. Treatment with AZT resulted in a treatment time-dependent reduction of viral RNA in the lungs of infected mice compared to untreated infected mice. The reduction of viral burden in the lungs correlated with a reduction in the severity of IP and decreased production of the proinflammatory cytokines interleukin (IL)-1beta and interferon (IFN)-gamma. These results suggest that continuous viral replication in the lung contributes to the pathogenesis of IP.