Le May Nicolas, Dubaele Sandy, Proietti De Santis Luca, Billecocq Agnès, Bouloy Michèle, Egly Jean-Marc
Unité de Génétique Moléculaire des Bunyaviridés, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris, Cedex 15, France.
Cell. 2004 Feb 20;116(4):541-50. doi: 10.1016/s0092-8674(04)00132-1.
The Rift Valley fever virus (RVFV) is the causative agent of fatal hemorrhagic fever in humans and acute hepatitis in ruminants. We found that infection by RVFV leads to a rapid and drastic suppression of host cellular RNA synthesis that parallels a decrease of the TFIIH transcription factor cellular concentration. Using yeast two hybrid system, recombinant technology, and confocal microscopy, we further demonstrated that the nonstructural viral NSs protein interacts with the p44 component of TFIIH to form nuclear filamentous structures that also contain XPB subunit of TFIIH. By competing with XPD, the natural partner of p44 within TFIIH, and sequestering p44 and XPB subunits, NSs prevents the assembly of TFIIH subunits, thus destabilizing the normal host cell life. These observations shed light on the mechanism utilized by RVFV to evade the host response.
裂谷热病毒（RVFV）是人类致命性出血热和反刍动物急性肝炎的病原体。我们发现，RVFV感染会导致宿主细胞RNA合成迅速且剧烈地受到抑制，这与TFIIH转录因子细胞浓度的降低相平行。利用酵母双杂交系统、重组技术和共聚焦显微镜，我们进一步证明，病毒非结构蛋白NSs与TFIIH的p44组分相互作用，形成也包含TFIIH的XPB亚基的核丝状结构。通过与TFIIH内p44的天然伴侣XPD竞争，并隔离p44和XPB亚基，NSs阻止了TFIIH亚基的组装，从而破坏了正常宿主细胞的生命活动。这些观察结果揭示了RVFV用于逃避宿主反应的机制。
