Zhang Zhi-Qiang, Casimiro Danilo R, Schleif William A, Chen Minchun, Citron Michael, Davies Mary-Ellen, Burns Janine, Liang Xiaoping, Fu Tong-Ming, Handt Larry, Emini Emilio A, Shiver John W
Department of Vaccines and Biologics Research, Merck Research Laboratories, West Point, PA 19486, USA.
Virology. 2007 May 10;361(2):455-64. doi: 10.1016/j.virol.2006.12.006. Epub 2007 Jan 16.
Lack of virus specific antibody response is commonly observed in both HIV-1-infected humans and SIV-infected monkeys with rapid disease progression. However, the mechanisms underlying this important observation still remain unclear. In a titration study of a SIVmac239 viral stock, three out of six animals with viral inoculation rapidly progressed to AIDS within 5 months. Unexpectedly, there was no obvious depletion of CD4(+) T cells in both peripheral and lymph node (LN) compartments in these animals. Instead, progressive depletion of proliferating B cells and disruption of the follicular dendritic cell (FDC) network in germinal centers (GC) was evident in the samples collected at as early as 20 days after viral challenge. This coincided with undetectable, or weak and transient, virus-specific antibody responses over the course of infection. In situ hybridization of SIV RNA in the LN samples revealed a high frequency of SIV productively infected cells and large amounts of accumulated viral RNA in the GCs in these animals. Early severe depletion of GC proliferating B cells and disruption of the FDC network may thus result in an inability to mount a virus-specific antibody response in rapid progressors, which has been shown to contribute to accelerated disease progression of SIV infection.
在疾病进展迅速的HIV-1感染人类和SIV感染猴子中，通常都观察到缺乏病毒特异性抗体反应。然而，这一重要观察结果背后的机制仍不清楚。在一项SIVmac239病毒储备液的滴定研究中，接种病毒的六只动物中有三只在5个月内迅速发展为艾滋病。出乎意料的是，这些动物的外周和淋巴结（LN）区室中的CD4(+) T细胞没有明显耗竭。相反，在病毒攻击后最早20天采集的样本中，生发中心（GC）中增殖B细胞的逐渐耗竭和滤泡树突状细胞（FDC）网络的破坏很明显。这与感染过程中无法检测到、或微弱且短暂的病毒特异性抗体反应相一致。LN样本中SIV RNA的原位杂交显示，这些动物的GC中有高频率的SIV有效感染细胞和大量积累的病毒RNA。因此，GC增殖B细胞的早期严重耗竭和FDC网络的破坏可能导致快速进展者无法产生病毒特异性抗体反应，这已被证明会导致SIV感染的疾病加速进展。
