The liver is a major organ for clearing simian immunodeficiency virus in rhesus monkeys
The liver is a major organ for clearing simian immunodeficiency virus in rhesus monkeys
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DOI：
10.1128/jvi.76.10.5271-5273.2002
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发表时间：
2002-05-01
影响因子：
5.4
通讯作者：
Ho, DD
中科院分区：
文献类型：
--
作者：
Zhang, LQ;Dailey, PJ;Ho, DD
人或猴免疫缺陷病毒（SIV）感染的特征是病毒颗粒和生产性感染细胞的快速更新。最近有报道称，SIV在体内的清除非常快，半衰期大约为几分钟。然而，负责这种快速清除的潜在机制或位点仍然未知。为了研究这个问题，我们选择输注从自体外周血单核细胞生长的感染性SIVmac 239，这些细胞被[S-35]甲硫氨酸和[S-35]半胱氨酸放射性标记。这种方法从病毒膜上消除了可能对病毒清除有显著影响的同种异体抗原。此外，这种方法还允许通过测量放射性强度来鉴定病毒清除的位点，即使SIV RNA在组织中发生降解。我们现在报告，在血液中注入的SIV的半衰期是非常接近的估计从以前的研究，其中未标记的SIV生长在异源细胞系中使用。因此，由于病毒体表面存在人抗原而产生的同种异体效应可能在病毒体高清除率中发挥最小作用。此外，近30%的输注放射性物质存在于肝脏中，在肺（5.4%）、淋巴结（3.0%）和脾脏（0.4%）中检测到可测量的量。在肝脏中检测到显著比例的输注病毒表明，循环中的病毒清除是由一种常见的非特异性机制介导的，如网状内皮系统的吞噬功能。外源注入的病毒粒子的快速清除和降解可能对使用病毒载体的基因治疗造成主要障碍，除非开发出克服这些粒子的快速体内消除的策略。
Infection with human or simian immunodeficiency virus (SIV) is characterized by the rapid turnover of both viral particles and productively infected cells. It has recently been reported that the clearance of SIV in vivo is exceedingly fast, with half-lives on the order of minutes. The underlying mechanism or site responsible for this rapid clearance, however, remains unknown. To investigate this issue, we chose to infuse infectious SIVmac239 grown from autologous peripheral blood mononuclear cells that were radioactively labeled by [S-35] methionine and [S-35] cysteine. This approach eliminates from the viral membrane alloantigens that may have a significant impact on viral clearance. In addition, this approach also permits identification of the sites of viral clearance by measuring the radioactive intensity, even if degradation of SIV RNA occurs in tissues. We now report that the half-life of infused SIV in blood is extremely close to estimates from a previous study, in which unlabeled SIV grown in a heterologous cell line was used. The allogeneic effect due to the presence of human antigens on the surfaces of virions may, therefore, play a minimal role in the high rate of virion clearance. Moreover, close to 30% of infused radioactivity was found in the liver and measureable amounts were detected in the lungs (5.4%), lymph nodes (3.0%), and spleen (0.4%). The detection of a significant proportion of infused virus in the liver suggests that viral clearance from circulation is mediated by a common, nonspecific mechanism, such as the phagocytic functions of the reticuloendothelial system. The rapid clearance and degradation of exogenously infused virions may pose a major obstacle for gene therapy with viral vectors, unless strategies to overcome the rapid in vivo elimination of these particles are developed.