title: Influenza A virus utilizes suboptimal splicing to coordinate the timing of infection.
abstract: Influenza A virus is unique as an RNA virus in that it replicates in the nucleus and undergoes splicing. With only ten major proteins, the virus must gain nuclear access, replicate, assemble progeny virions in the cytoplasm, and then egress. In an effort to elucidate the coordination of these events, we manipulated the transcript levels from the bicistronic nonstructural segment that encodes the spliced virus product responsible for genomic nuclear export. We find that utilization of an erroneous splice site ensures the slow accumulation of the viral nuclear export protein (NEP) while generating excessive levels of an antagonist that inhibits the cellular response to infection. Modulation of this simple transcriptional event results in improperly timed export and loss of virus infection. Together, these data demonstrate that coordination of the influenza A virus life cycle is set by a "molecular timer" that operates on the inefficient splicing of a virus transcript.
authors: Microbiology Graduate School Training Program, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors: Mark A
authors: MA
authors: Chua
authors: Sonja
authors: S
authors: Schmid
authors: Jasmine T
authors: JT
authors: Perez
authors: Ryan A
authors: RA
authors: Langlois
authors: Benjamin R
authors: BR
authors: Tenoever
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D020868:Gene Silencing; D009980:Influenza A virus / Q000235:genetics* / Q000502:physiology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000235:genetics* / Q000821:virology*; D012326:RNA Splicing / Q000235:genetics*; D034741:RNA, Small Interfering / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: C085820:INS1 protein, influenza virus; D035683:MicroRNAs; D034741:RNA, Small Interfering; D012261:Ribonucleoproteins; D017361:Viral Nonstructural Proteins