the splicing factor proline-glutamine rich (sfpqpsf) is involved in influenza virus transcription剪接因子proline-glutamine丰富(sfpqpsf)流感病毒转录.pdfVIP

The Splicing Factor Proline-Glutamine Rich (SFPQ/PSF) Is Involved in Influenza Virus Transcription 1,2 ´ 1,2¤ ´ 1,2 ´ 1,2 Sara Landeras-Bueno , Nuria Jorba , Maite Perez-Cidoncha , Juan Ortın * ´ 1 Centro Nacional de Biotecnologıa (CSIC), Campus de Cantoblanco, Madrid, Spain, 2 CIBER de Enfermedades Respiratorias, ISCIII, Bunyola, Mallorca, Spain Abstract The influenza A virus RNA polymerase is a heterotrimeric complex responsible for viral genome transcription and replication in the nucleus of infected cells. We recently carried out a proteomic analysis of purified polymerase expressed in human cells and identified a number of polymerase-associated cellular proteins. Here we characterise the role of one such host factors, SFPQ/PSF, during virus infection. Down-regulation of SFPQ/PSF by silencing with two independent siRNAs reduced the virus yield by 2–5 log in low-multiplicity infections, while the replication of unrelated viruses as VSV or Adenovirus was almost unaffected. As the SFPQ/PSF protein is frequently associated to NonO/p54, we tested the potential implication of the latter in influenza virus replication. However, down-regulation of NonO/p54 by silencing with two independent siRNAs did not affect virus yields. Down-regulation of SFPQ/PSF by siRNA silencing led to a reduction and delay of influenza virus gene expression. Immunofluorescence analyses showed a good correlation between SFPQ/PSF and NP levels in infected cells. Analysis of virus RNA accumulation in silenced cells showed that production of mRNA, cRNA and vRNA is reduced by more than 5-fold but splicing is not affected. Likewise, the accumulation of viral mRNA in cicloheximide-treated cells was reduced by