PMID: 10590087Dec 10, 1999Paper

Mutagenesis of the signal sequence of yellow fever virus prM protein: enhancement of signalase cleavage In vitro is lethal for virus production

Journal of Virology
Eva LeeM Lobigs

Abstract

Proteolytic processing at the C-prM junction in the flavivirus polyprotein involves coordinated cleavages at the cytoplasmic and luminal sides of an internal signal sequence. We have introduced at the COOH terminus of the yellow fever virus (YFV) prM signal sequence amino acid substitutions (VPQAQA mutation) which uncoupled efficient signal peptidase cleavage of the prM protein from its dependence on prior cleavage in the cytoplasm of the C protein mediated by the viral NS2B-3 protease. Infectivity assays with full-length YFV RNA transcripts showed that the VPQAQA mutation, which enhanced signal peptidase cleavage in vitro, was lethal for infectious virus production. Revertants or second-site mutants were recovered from cells transfected with VPQAQA RNA. Analysis of these viruses revealed that single amino acid substitutions in different domains of the prM signal sequence could restore viability. These variants had growth properties in vertebrate cells which differed only slightly from those of the parent virus, despite efficient signal peptidase cleavage of prM in cell-free expression assays. However, the neurovirulence in mice of the VPQAQA variants was significantly attenuated. This study demonstrates that substitutions in t...Continue Reading

References

May 1, 1990·The Journal of Membrane Biology·G von Heijne
Jun 9, 1988·Biochimica Et Biophysica Acta·G von Heijne
Jun 11, 1986·Nucleic Acids Research·G von Heijne
Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·M Lobigs
Jan 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·P M ZanottoE C Holmes
Jun 1, 1997·Protein Science : a Publication of the Protein Society·R E DalbeyJ M van Dijl
Nov 21, 1998·Nature·G von Heijne
Jun 25, 1999·Cell·M Pilon, R Schekman

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Citations

Apr 6, 2004·Immunology and Cell Biology·Mario LobigsEva Lee
Feb 14, 2004·Journal of Virology·Poonsook KeelapangNopporn Sittisombut
Mar 7, 2002·Proceedings of the National Academy of Sciences of the United States of America·Alexander G PletnevDavid W Vaughn
Feb 11, 2004·Proceedings of the National Academy of Sciences of the United States of America·Regina M KoflerChristian W Mandl
Jun 25, 2014·Archives of Virology·Charmaine van EedenMarietjie Venter
Aug 7, 2013·Science China. Life Sciences·PeiPei LiuJingLiang Su
Jan 13, 2015·The Journal of General Virology·Xiao-Dan LiBo Zhang
Feb 26, 2015·The Journal of General Virology·Justin A RobyAlexander A Khromykh
Dec 3, 2014·Current Opinion in Virology·Swapna Apte-SenguptaRichard J Kuhn
Feb 9, 2008·Emerging Infectious Diseases·Elizabeth M BothaMarietjie Venter
Oct 24, 2009·PLoS Pathogens·Marcelo M SamsaAndrea V Gamarnik
Mar 24, 2015·Antiviral Research·Xuping XiePei-Yong Shi
May 31, 2011·Vaccine·Alexander A RumyantsevKonstantin V Pugachev
Aug 9, 2016·Annual Review of Virology·Laura A Byk, Andrea V Gamarnik
Jan 15, 2003·Journal of Medical Virology·Takanobu KatoTakaji Wakita
Feb 13, 2018·Nature Reviews. Microbiology·Christopher J NeufeldtRalf Bartenschlager

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