TFIIH Transcription Factor, a Target for the Rift Valley Hemorrhagic Fever Virus¹

Speaker: 姚蕙雯

Commentator: 陳舜華  老師

Date: 2004/ 05/ 12   15:00-16:00

Abstract:

The Rift Valley Fever Virus (RVFV), an arbovirus with high pathogenicity for humans and ruminants, is a member of the Bunyaviridae which has segmented, negative single-stranded RNA genome.  Upon infection, RVFV can cause a broad spectrum of clinical symptoms, like severe encephalitis, fatal hepatitis and hemorrhagic fever.  Since RVFV was first reported among livestock in Kenya in the early 1900s, the pathogenesis of RVFV infection was not known well.  Some cytopathic RNA viruses, like poliovirus and vesicular stomatitis virus, can inhibit the host transcription machinery without affecting its own replication.²   In this study, the authors wanted to know if RVFV has the same effect on cellular functions.  First, they infected HeLa cells with RVFV and found that the RNA synthesis in infected cells was inhibited by the virulent strain, ZH548, which expressed wild-type nonstructural proteins (NSs), but not by the avirulent strain, C13.  Using cDNA library screening, they found that NSs inhibited host RNA synthesis by interacting with p44, a subunit of TFIIH.  TFIIH is a basal transcription factor with multisubunit structure, and also involves in DNA repair and the regulation of cell cycle.³  During RVFV ZH548 infection, the cellular concentration of TFIIH was decreased in infected cells because some of its subunits, p44 and XPB, formed filamentous structures with NSs in the nucleus.  At the same time, there were abnormal accumulations of another subunit of TFIIH, XPD, around the nuclear membrane in infected cells.  By sequestering the subunits of TFIIH in the nuclear filamentous structures, the formation of functional TFIIH complexes was limited in infected cells.  Thus, TFIIH transcription factor was a target for viral NSs in the pathogenesis of RVFV infection.

References:

1.     Le May, N., Dubaele, S., De Santis, LP., Billecocq, A., Bouloy, M., and Egly, JM. 2004. TFIIH transcription factor, a target for the Rift Valley Hemorrhagic Fever Virus. Cell. 116(4): 541-50.

2.     Lyles, DS. 2000. Cytopathogenesis and inhibition of host gene expression by RNA viruses. Microbiol. Mol. Biol. Rev. 64(4): 709-24.

3.     Zurita, M., and Merino, C. 2003. The transcriptional complexity of the TFIIH complex. Trends Genet. 19(10): 578-84.