In vivo assessment of NS1-truncated influenza virus with a novel SLSYSINWRH motif as a self-adjuvanting live attenuated vaccine

PloS One
John M NgunjiriChang-Won Lee

Abstract

Mutants of influenza virus that encode C-terminally truncated NS1 proteins (NS1-truncated mutants) characteristically induce high interferon responses. The dual activity of interferon in blocking virus replication and enhancing the development of adaptive immune responses makes these mutants promising as self-adjuvanting live-attenuated influenza vaccine (LAIV) candidates. Yet, among the NS1-truncated mutants, the length of NS1 is not directly correlated with the interferon-inducing efficiency, the level of attenuation, or effectiveness as LAIV. Using quantitative in vitro biologically active particle subpopulation analysis as a tool to identify potential LAIV candidates from a pool of NS1-truncated mutants, we previously predicted that a NS1-truncated mutant pc2, which was less effective as a LAIV in chickens, would be sufficiently effective as a LAIV in mammalian hosts. In this study, we confirmed that pc2 protected mice and pigs against heterologous virus challenge in terms of preventing clinical signs and reducing virus shedding. pc2 expresses a unique SLSYSINWRH motif at the C-terminus of its truncated NS1. Deletion of the SLSYSINWRH motif led to ~821-fold reduction in the peak yield of type I interferon induced in murine ...Continue Reading

References

Sep 1, 1988·Nurse Educator·D Johnson, L Jordan
Oct 22, 1998·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Y NagaoA Uemura
Jul 19, 2001·Nature·D Cyranoski
Aug 25, 2001·Rinsho byori. The Japanese journal of clinical pathology·A Oya
Oct 24, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·H F StaatsB F Haynes
Jun 14, 2002·Acta Tropica·Ilaria CapuaFrancesco Maria Cancellotti
Jun 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Enrico ProiettiFilippo Belardelli
Jun 29, 2002·Current Opinion in Immunology·Agnes Le Bon, David F Tough
Jul 3, 2002·The Journal of Clinical Investigation·Peter Palese, Adolfo García-Sastre
Aug 9, 2003·BMJ : British Medical Journal·Jane Parry
Sep 23, 2003·Nature Immunology·Agnes Le BonDavid F Tough
Oct 25, 2003·Avian Diseases·G NeumannY Kawaoka
Jan 28, 2004·Proceedings of the National Academy of Sciences of the United States of America·Ron A M FouchierAlbert D M E Osterhaus
Feb 15, 2005·Journal of Virology·Philip I MarcusMargaret J Sekellick
Jun 16, 2005·Journal of Virology·Michelle QuinlivanPeter Palese
Sep 30, 2005·The New England Journal of Medicine·John H BeigelUNKNOWN Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5
Apr 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Agnes Le BonDavid F Tough
Dec 15, 2006·The New England Journal of Medicine·Suzanne E OhmitArnold S Monto
Jan 5, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Timothy J PowellRichard W Dutton
Apr 7, 2007·The Journal of General Virology·Georg KochsPeter Staeheli
Jun 5, 2007·Vaccine·Noelle-Angelique M MolinariCarolyn B Bridges
Nov 7, 2008·Nature·Zachary A Bornholdt, B V Venkataram Prasad
Dec 17, 2008·Advances in Virus Research·Amy L VincentJürgen A Richt
Jun 3, 2009·Zoonoses and Public Health·W MaJ A Richt
May 26, 2010·Clinical Genetics·T JaijoJ M Millán
Mar 2, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mark W LaMereDenise A Kaminski
Apr 12, 2011·Influenza and Other Respiratory Viruses·Gabriele Neumann, Yoshihiro Kawaoka

❮ Previous
Next ❯

Methods Mentioned

BETA
reverse transcription PCR
Cesarean-section
PCR
transfection

Software Mentioned

GraphPad Prism
FluMist
GraphPad

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.