Viral escape from antisense RNA

Molecular Microbiology
J J BullI J Molineux

Abstract

RNA coliphage SP was propagated for several generations on a host expressing an inhibitory antisense RNA complementary to bases 31-270 of the positive-stranded genome. Phages evolved that escaped inhibition. Typically, these escape mutants contained 3-4 base substitutions, but different sequences were observed among different isolates. The mutations were located within three different types of structural features within the predicted secondary structure of SP genomic RNA: (i) hairpin loops; (ii) hairpin stems; and (iii) the 5' region of the phage genome complementary to the antisense molecule. Computer modelling of the mutant genomic RNAs showed that all of the substitutions within hairpin stems improved the Watson-Crick pairing of the stem. No major structural rearrangements were predicted for any of the mutant genomes, and most substitutions in coding regions did not alter the amino acid sequence. Although the evolved phage populations were polymorphic for substitutions, many substitutions appeared independently in two selected lines. The creation of a new, perfect, antisense RNA against an escape mutant resulted in the inhibition of that mutant but not of other escape mutants nor of the ancestral, unevolved phage. Thus, at l...Continue Reading

References

Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·T M WoolfC G Jennings
Aug 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·D Herschlag
Oct 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·A HirashimaM Inouye
Jul 11, 1988·Nucleic Acids Research·Y InokuchiA Hirashima
Jan 1, 1994·Methods in Molecular Biology·M Zuker
Sep 27, 1994·Proceedings of the National Academy of Sciences of the United States of America·A E WalterM Zuker
Jan 1, 1994·Annual Review of Microbiology·E G Wagner, R W Simons
Sep 20, 1993·Journal of Molecular Biology·A B Jacobson, M Zuker
Feb 16, 1996·Journal of Molecular Biology·J BeekwilderJ van Duin
Apr 1, 1996·Journal of Medical Virology·F Y Tung, M H Tung
Jan 1, 1996·Antisense & Nucleic Acid Drug Development·Z F FuH Koprowski
Jan 1, 1997·Molecular Medicine Today·R W Wagner, W M Flanagan
Mar 1, 1997·The Journal of General Virology·J Wu, M A Gerber
Apr 18, 1997·Journal of Molecular Biology·M HuynenD Konings
May 1, 1997·Journal of Viral Hepatitis·W Ji, C W Si
Jul 1, 1997·The Journal of Infectious Diseases·A F BellR S Fujinami
Jan 1, 1997·Advances in Pharmacology·R E Kilkuskie, A K Field
Jul 1, 1996·Nature Biotechnology·R W WagnerB C Froehler

❮ Previous
Next ❯

Citations

Feb 26, 2004·Antimicrobial Agents and Chemotherapy·Hwijin Kim, John Yin
May 23, 2006·Nature Reviews. Microbiology·Joseph M Sturino, Todd R Klaenhammer
Mar 18, 2000·Antimicrobial Agents and Chemotherapy·D Endy, J Yin
Mar 10, 2004·Applied and Environmental Microbiology·Joseph M Sturino, Todd R Klaenhammer
Jun 10, 2009·Immunology and Cell Biology·Donald R Forsdyke
Feb 13, 2001·Gene·D R Forsdyke, J R Mortimer
Oct 12, 2000·Clinical Microbiology Reviews·C D BlairK E Olson
Sep 15, 2004·Journal of Molecular Biology·I S NovellaB E Ebendick-Corpus

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bacteriophage: Phage Therapy

Phage therapy uses bacterial viruses (bacteriophages) to treat bacterial infections and is widely being recognized as an alternative to antibiotics. Here is the latest research.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Bacterial Respiration

This feed focuses on cellular respiration in bacteria, known as bacterial respiration. Discover the latest research here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.