The splicing factor proline-glutamine rich (SFPQ/PSF) is involved in influenza virus transcription

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 3-fold. in contrast,down-regulation of sfpq/psf in a recombinant virus replicon system indicated that,while the accumulation of viral mrna is reduced by 5-fold,vrna levels are slightly increased. in vitro transcription of recombinant rnps generated in sfpq/psf-silenced cells indicated a 4-5-fold reduction in polyadenylation but no alteration in cap snatching. these results indicate that sfpq/psf is a host factor essential for influenza virus transcription that increases the efficiency of viral mrna polyadenylation and open the possibility to develop new antivirals targeting the accumulation of primary transcripts,a very early step during infection. © 2011 landeras-bueno et al.