Rapid dissemination of a pathogenic simian/human immunodeficiency virus to systemic organs and active replication in lymphoid tissues following intrarectal infection
Rapid dissemination of a pathogenic simian/human immunodeficiency virus to systemic organs and active replication in lymphoid tissues following intrarectal infection
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DOI：
10.1099/vir.0.81307-0
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发表时间：
2006-05-01
影响因子：
3.8
通讯作者：
Hayami, M
中科院分区：
文献类型：
--
作者：
Miyake, A;Ibuki, K;Hayami, M
更好地了解人类免疫缺陷病毒1（HIV-1）感染早期的病毒学事件对于开发有效的抗病毒疫苗非常重要。在这项研究中，通过使用定量PCR和感染性空斑试验，病毒的分布和复制进行了检查，在各种内部器官的恒河猴，猕猴近1个月后，直肠内接种的致病性猴免疫缺陷病毒/HIV嵌合病毒（SHIV-C2/ 1-KS 661 c）。在接种后3天（p.i.），在直肠、胸腺和腋窝淋巴结中检测到前病毒DNA。在淋巴组织中，感染后第6天首次检测到感染性病毒。在感染后13天检测到高水平的前病毒DNA和感染性病毒。到感染后27天，尽管前病毒DNA载量保持不变，但传染性病毒的水平急剧下降。在肠道中，检测到的感染性病毒水平远低于淋巴组织，而在整个感染过程中，在淋巴组织中检测到的前病毒DNA水平相同。在胸腺和空肠中，CD 4CD 8双阳性T细胞比CD 4单阳性细胞更早耗尽。这些结果表明，病毒在粘膜传播后迅速扩散到全身组织。此后，感染性病毒在淋巴组织中活跃产生，但在病毒血症高峰后水平显著下降。相反，在肠道中，感染性病毒从感染开始就以低水平产生。此外，在CD 4单阳性和CD 4CD 8双阳性T细胞中，病毒的发病机制不同。
A better understanding of virological events during the early phase of human immunodeficiency virus 1 (HIV-1) infection is important for development of effective antiviral vaccines. In this study, by using quantitative PCR and an infectious plaque assay, virus distribution and replication were examined in various internal organs of rhesus; macaques for almost 1 month after intrarectal inoculation of a pathogenic simian immunodeficiency virus/HIV chimeric virus (SHIV-C2/ 1-KS661c). At 3 days post-inoculation (p.i.), proviral DNA was detected in the rectum, thymus and axillary lymph node. In lymphoid tissues, infectious virus was first detected at 6 days p.i. and a high level of proviral DNA and infectious virus were both detected at 13 days p.i. By 27 days p.i., levels of infectious virus decreased dramatically, although proviral DNA load remained unaltered. In the intestinal tract, levels of infectious virus detected were much lower than in lymphoid tissues, whereas proviral DNA was detected at the same level as in lymphoid tissues throughout the infection. In the thymus and jejunum, CD4CD8 double-positive T cells were depleted earlier than CD4 single-positive cells. These results show that the virus spread quickly to systemic tissues after mucosal transmission. Thereafter, infectious virus was actively produced in the lymphoid tissues, but levels decreased significantly after the peak of viraemia. In contrast, in the intestinal tract, infectious virus was produced at low levels from the beginning of infection. Moreover, virus pathogenesis differed in CD4 single-positive and CD4CD8 double-positive T cells.