Melzi Eleonora, Caporale Marco, Rocchi Mara, Martín Verónica, Gamino Virginia, di Provvido Andrea, Marruchella Giuseppe, Entrican Gary, Sevilla Noemí, Palmarini Massimo
MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, Scotland.
MRC-University of Glasgow Centre for Virus Research, Glasgow G61 1QH, Scotland; Istituto Zooprofilattico Sperimentale dell'Abruzzo e Molise "G. Caporale", 64100 Teramo, Italy.
Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):E6238-E6247. doi: 10.1073/pnas.1610012113. Epub 2016 Sep 26.
Arboviruses cause acute diseases that increasingly affect global health. We used bluetongue virus (BTV) and its natural sheep host to reveal a previously uncharacterized mechanism used by an arbovirus to manipulate host immunity. Our study shows that BTV, similarly to other antigens delivered through the skin, is transported rapidly via the lymph to the peripheral lymph nodes. Here, BTV infects and disrupts follicular dendritic cells, hindering B-cell division in germinal centers, which results in a delayed production of high affinity and virus neutralizing antibodies. Moreover, the humoral immune response to a second antigen is also hampered in BTV-infected animals. Thus, an arbovirus can evade the host antiviral response by inducing an acute immunosuppression. Although transient, this immunosuppression occurs at the critical early stages of infection when a delayed host humoral immune response likely affects virus systemic dissemination and the clinical outcome of disease.
虫媒病毒引发的急性疾病对全球健康的影响日益增大。我们利用蓝舌病病毒（BTV）及其天然宿主绵羊，揭示了一种此前未被描述的虫媒病毒操纵宿主免疫的机制。我们的研究表明，与通过皮肤递送的其他抗原类似，BTV通过淋巴迅速转运至外周淋巴结。在此，BTV感染并破坏滤泡树突状细胞，阻碍生发中心的B细胞分裂，导致高亲和力和病毒中和抗体的产生延迟。此外，在感染BTV的动物中，对第二种抗原的体液免疫反应也受到阻碍。因此，一种虫媒病毒可通过诱导急性免疫抑制来逃避宿主的抗病毒反应。尽管这种免疫抑制是短暂的，但它发生在感染的关键早期阶段，此时宿主体液免疫反应延迟可能会影响病毒的全身传播和疾病的临床结局。
