Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USA.
Immunology. 2013 Oct;140(2):168-78. doi: 10.1111/imm.12116.
Pathogenic New World hantaviruses cause severe disease in humans characterized by a vascular leak syndrome, leading to pulmonary oedema and respiratory distress with case fatality rates approaching 40%. Hantaviruses infect microvascular endothelial cells without conspicuous cytopathic effects, indicating that destruction of the endothelium is not a mechanism of disease. In humans, high levels of inflammatory cytokines are present in the lungs of patients that succumb to infection. This, along with other observations, suggests that disease has an immunopathogenic component. Currently the only animal model available to study hantavirus disease is the Syrian hamster, where infection with Andes virus (ANDV), the primary agent of disease in South America, results in disease that closely mimics that seen in humans. Conversely, inoculation of hamsters with a passaged Sin Nombre virus (SNV), the virus responsible for most cases of disease in North America, results in persistent infection with high levels of viral replication. We found that ANDV elicited a stronger innate immune response, whereas SNV elicited a more robust adaptive response in the lung. Additionally, ANDV infection resulted in significant changes in the blood lymphocyte populations. To determine whether the adaptive immune response influences infection outcome, we depleted hamsters of CD4(+) and CD8(+) T cells before infection with hantaviruses. Depletion resulted in inhibition of virus-specific antibody responses, although the pathogenesis and replication of these viruses were unaltered. These data show that neither hantavirus replication, nor pathogenesis caused by these viruses, is influenced by the adaptive immune response in the Syrian hamster.
新世界汉坦病毒会导致人类患上严重疾病，其特征为血管渗漏综合征，导致肺水肿和呼吸窘迫，病死率接近 40%。汉坦病毒感染微血管内皮细胞而没有明显的细胞病变效应，这表明内皮细胞的破坏不是疾病的机制。在人类中，感染后肺部会出现高水平的炎症细胞因子。这一点，以及其他观察结果，表明疾病具有免疫发病机制成分。目前，可用于研究汉坦病毒病的唯一动物模型是叙利亚仓鼠，感染安第斯病毒（ANDV），即南美洲主要病原体，会导致与人类所见非常相似的疾病。相反，接种经过传代的辛诺柏病毒（SNV）（导致北美的大多数病例）会导致持续性感染和高水平的病毒复制。我们发现，ANDV 引发了更强的先天免疫反应，而 SNV 则在肺部引发了更强大的适应性反应。此外，ANDV 感染导致血液淋巴细胞群发生显著变化。为了确定适应性免疫反应是否会影响感染结果，我们在感染汉坦病毒之前耗尽了仓鼠的 CD4(+)和 CD8(+)T 细胞。耗竭导致病毒特异性抗体反应受到抑制，尽管这些病毒的发病机制和复制未受影响。这些数据表明，在叙利亚仓鼠中，适应性免疫反应既不会影响汉坦病毒的复制，也不会影响这些病毒引起的发病机制。
