tetano
Editor, Senior Moderator
Cell Rep. 2013 Jan 15. pii: S2211-1247(12)00454-8. doi: 10.1016/j.celrep.2012.12.010. [Epub ahead of print]
Influenza A Virus Utilizes Suboptimal Splicing to Coordinate the Timing of Infection.
Chua MA, Schmid S, Perez JT, Langlois RA, Tenoever BR.
Source
Microbiology Graduate School Training Program, Mount Sinai School of Medicine, New York, NY 10029, USA.
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.
Copyright ? 2013 The Authors. Published by Elsevier Inc. All rights reserved.
PMID:
23333274
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23333274
Influenza A Virus Utilizes Suboptimal Splicing to Coordinate the Timing of Infection.
Chua MA, Schmid S, Perez JT, Langlois RA, Tenoever BR.
Source
Microbiology Graduate School Training Program, Mount Sinai School of Medicine, New York, NY 10029, USA.
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.
Copyright ? 2013 The Authors. Published by Elsevier Inc. All rights reserved.
PMID:
23333274
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23333274