Zhang Linqi, Dailey Peter J, Gettie Agegnehu, Blanchard Jim, Ho David D
Aaron Diamond AIDS Research Center and The Rockefeller University, New York, New York 10016, USA.
J Virol. 2002 May;76(10):5271-3. doi: 10.1128/jvi.76.10.5271-5273.2002.
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 [(35)S]methionine and [(35)S]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.
人类免疫缺陷病毒（HIV）或猿猴免疫缺陷病毒（SIV）感染的特征是病毒颗粒和被感染的细胞快速更新。最近有报道称，SIV在体内的清除速度极快，半衰期仅为几分钟。然而，导致这种快速清除的潜在机制或部位仍不清楚。为了研究这个问题，我们选择注入从经[(35)S]甲硫氨酸和[(35)S]半胱氨酸放射性标记的自体外周血单核细胞中培养出的感染性SIVmac239。这种方法消除了病毒膜上可能对病毒清除有重大影响的同种异体抗原。此外，即使SIV RNA在组织中发生降解，这种方法也能通过测量放射性强度来确定病毒清除的部位。我们现在报告，注入血液中的SIV的半衰期与先前一项研究的估计值极为接近，在该研究中使用的是在异源细胞系中培养的未标记SIV。因此，病毒颗粒表面存在人类抗原所导致的同种异体效应在病毒颗粒的高清除率中可能只起很小的作用。此外，在肝脏中发现了近30%注入的放射性物质，在肺（5.4%）、淋巴结（3.0%）和脾脏（0.4%）中也检测到了可测量的量。在肝脏中检测到相当一部分注入的病毒表明，循环中病毒的清除是由一种常见的非特异性机制介导的，比如网状内皮系统的吞噬功能。外源性注入的病毒颗粒的快速清除和降解可能对病毒载体基因治疗构成重大障碍，除非开发出克服这些颗粒在体内快速清除的策略。
