The A66G back mutation in NS2A of JEV SA 14 -14-2 strain contributes to production of NS1′ protein and the secreted NS1′ can be used for diagnostic biomarker for virulent virus infection

2015 ◽  
Vol 36 ◽  
pp. 116-125 ◽  
Author(s):  
Jingman Wang ◽  
Xinfeng Li ◽  
Jinyan Gu ◽  
Yu Fan ◽  
Peng Zhao ◽  
...  
Keyword(s):  
Virus Infection ◽  
Ns1 Protein ◽  
Diagnostic Biomarker ◽  
Back Mutation ◽  
Virulent Virus

Role of the chaperone protein 14-3-3ε in the regulation of influenza A virus-activated beta interferon

2021 ◽  
Author(s):  
Ee-Hong Tam ◽  
Yen-Chin Liu ◽  
Chian-Huey Woung ◽  
Helene Minyi Liu ◽  
Guan-Hong Wu ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Critical Role ◽  
Type I ◽  
Type I Ifn ◽  
Ns1 Protein ◽  
Chaperone Protein ◽  
Influenza A Virus Infection

The NS1 protein of the influenza A virus plays a critical role in regulating several biological processes in cells, including the type I interferon (IFN) response. We previously profiled the cellular factors that interact with the NS1 protein of influenza A virus and found that the NS1 protein interacts with proteins involved in RNA splicing/processing, cell cycle regulation, and protein targeting processes, including 14-3-3ε. Since 14-3-3ε plays an important role in RIG-I translocation to MAVS to activate type I IFN expression, the interaction of the NS1 and 14-3-3ε proteins may prevent the RIG-I-mediated IFN response. In this study, we confirmed that the 14-3-3ε protein interacts with the N-terminal domain of the NS1 protein and that the NS1 protein inhibits RIG-I-mediated IFN-β promoter activation in 14-3-3ε-overexpressing cells. In addition, our results showed that knocking down 14-3-3ε can reduce IFN-β expression elicited by influenza A virus and enhance viral replication. Furthermore, we found that threonine in the 49 th amino acid position of the NS1 protein plays a role in the interaction with 14-3-3ε. Influenza A virus expressing C-terminus-truncated NS1 with T49A mutation dramatically increases IFN-β mRNA in infected cells and causes slower replication than that of virus without the T-to-A mutation. Collectively, this study demonstrates that 14-3-3ε is involved in influenza A virus-initiated IFN-β expression and that the interaction of the NS1 protein and 14-3-3ε may be one of the mechanisms for inhibiting type I IFN activation during influenza A virus infection. IMPORTANCE Influenza A virus is an important human pathogen causing severe respiratory disease. The virus has evolved several strategies to dysregulate the innate immune response and facilitate its replication. We demonstrate that the NS1 protein of influenza A virus interacts with the cellular chaperone protein 14-3-3ε, which plays a critical role in RIG-I translocation that induces type I IFN expression, and that NS1 protein prevents RIG-I translocation to mitochondrial membrane. The interaction site for 14-3-3ε is the RNA-binding domain (RBD) of the NS1 protein. Therefore, this research elucidates a novel mechanism by which the NS1 RBD mediates IFN-β suppression to facilitate influenza A viral replication. Additionally, the findings reveal the antiviral role of 14-3-3ε during influenza A virus infection.

scholarly journals INFLUENCE OF AGE FACTORS ON IMMUNIZABILITY OF MICE TO RABIES VIRUS

1940 ◽  
Vol 72 (4) ◽  
pp. 453-461 ◽  
Author(s):  
J. Casals
Keyword(s):  
Virus Infection ◽  
Rabies Virus ◽  
Neutralizing Antibodies ◽  
Age Factors ◽  
Swiss Mice ◽  
Virulent Virus ◽  
Rabies Virus Infection

1. W-Swiss mice 60 or more days old are more readily immunizable against rabies virus infection than 20 day old or younger mice; this difference in immunizability with increasing age is most conspicuous when vaccination with virulent virus is followed by intracerebral test infection and least apparent when vaccination with avirulent virus is followed by intramuscular test infection. 2. The titre of circulating neutralizing antibodies does not parallel the titre of immunity.

scholarly journals Current Understanding of the Pathogenesis of Dengue Virus Infection

2020 ◽  
Author(s):  
Puneet Bhatt ◽  
Sasidharan Pillai Sabeena ◽  
Muralidhar Varma ◽  
Govindakarnavar Arunkumar
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Virus Infection ◽  
Dengue Virus ◽  
Genetic Factors ◽  
Host Immune Response ◽  
Severe Dengue ◽  
Ns1 Protein ◽  
Dengue Virus Infection ◽  
Antibody Dependent Enhancement

AbstractThe pathogenesis of dengue virus infection is attributed to complex interplay between virus, host genes and host immune response. Host factors such as antibody-dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1 antibodies, autoimmunity as well as genetic factors are major determinants of disease susceptibility. NS1 protein and anti-DENV NS1 antibodies were believed to be responsible for pathogenesis of severe dengue. The cytokine response of cross-reactive CD4+ T cells might be altered by the sequential infection with different DENV serotypes, leading to further elevation of pro-inflammatory cytokines contributing a detrimental immune response. Fcγ receptor-mediated antibody-dependent enhancement (ADE) results in release of cytokines from immune cells leading to vascular endothelial cell dysfunction and increased vascular permeability. Genomic variation of dengue virus and subgenomic flavivirus RNA (sfRNA) suppressing host immune response are viral determinants of disease severity. Dengue infection can lead to the generation of autoantibodies against DENV NS1antigen, DENV prM, and E proteins, which can cross-react with several self-antigens such as plasminogen, integrin, and platelet cells. Apart from viral factors, several host genetic factors and gene polymorphisms also have a role to play in pathogenesis of DENV infection. This review article highlights the various factors responsible for the pathogenesis of dengue and also highlights the recent advances in the field related to biomarkers which can be used in future for predicting severe disease outcome.

THE EVOLUTIONARY ADVANTAGE OF BREEDING FOR TOLERANCE OVER RESISTANCE AGAINST VIRAL PLANT DISEASE

1999 ◽  
Vol 47 (3) ◽  
pp. 135-139 ◽  
Author(s):  
Raffi Salomon
Keyword(s):  
Virus Infection ◽  
Selection Pressure ◽  
Virus Population ◽  
Long Run ◽  
Virulent Type ◽  
Evolutionary Advantage ◽  
Virulent Virus ◽  
Large Virus ◽  
Minimal Damage ◽  
Virus Mutant

A tolerant strain of a crop permits the propagation of an entire virus population, thus exerting a much lower selection pressure in favor of a virus mutant overcoming resistance. One may suppose that a tolerant crop may build up a large virus reservoir and therefore increase the chance of emergence of a more virulent type. However, the tolerant crop exerts a much lower selective pressure for a given virus line, and therefore the new virulent type remains a very low proportion of the total virus population. Susceptible crops, into which resistance to a given virus was bred, may be immune to this virus infection, thus preventing the buildup of a large virus reservoir. However, other host crops around it, or wild weeds facilitate propagation of this virus. This peripheral buildup of virus reservoir in the vicinity of the resistant crop creates a strong selection pressure for the propagation of the mutants overcoming resistance. Therefore, the planting of monoculture of a resistant crop accelerates the emergence of virulent virus lines that overcome this resistance. There is no reason to assume that resistance introduced into transgenic plants will be different. In the long run, tolerant crops may have the advantage over resistant crops, preserving for a longer time conditions in which virus infection causes only minimal damage. The production of tolerance to virus infection is an approach not yet favored by breeders and seed producers. However, it may be regarded as a less expensive, additional route to reduce the damage to crops inflicted by viral diseases.

Bluetongue virus serotype 8 virus-like particles protect sheep against virulent virus infection as a single or multi-serotype cocktail immunogen

Vaccine ◽  
2013 ◽  
Vol 31 (3) ◽  
pp. 553-558 ◽  
Author(s):  
Meredith Stewart ◽  
Eric Dubois ◽  
Corinne Sailleau ◽  
Emmanuel Bréard ◽  
Cyril Viarouge ◽  
...  
Keyword(s):  
Virus Infection ◽  
Bluetongue Virus ◽  
Virus Like Particles ◽  
Virus Serotype ◽  
Virulent Virus

scholarly journals DDX3 Interacts with Influenza A Virus NS1 and NP Proteins and Exerts Antiviral Function through Regulation of Stress Granule Formation

2016 ◽  
Vol 90 (7) ◽  
pp. 3661-3675 ◽  
Author(s):  
Sathya N. Thulasi Raman ◽  
Guanqun Liu ◽  
Hyun Mi Pyo ◽  
Ya Cheng Cui ◽  
Fang Xu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Life Cycle ◽  
Virus Infection ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Ns1 Protein ◽  
Antiviral Protein ◽  
Virus Life Cycle ◽  
Interaction Partners ◽  
Infected Cells

ABSTRACTDDX3 belongs to the DEAD box RNA helicase family and is a multifunctional protein affecting the life cycle of a variety of viruses. However, its role in influenza virus infection is unknown. In this study, we explored the potential role of DDX3 in influenza virus life cycle and discovered that DDX3 is an antiviral protein. Since many host proteins affect virus life cycle by interacting with certain components of the viral machinery, we first verified whether DDX3 has any viral interaction partners. Immunoprecipitation studies revealed NS1 and NP as direct interaction partners of DDX3. Stress granules (SGs) are known to be antiviral and do form in influenza virus-infected cells expressing defective NS1 protein. Additionally, a recent study showed that DDX3 is an important SG-nucleating factor. We thus explored whether DDX3 plays a role in influenza virus infection through regulation of SGs. Our results showed that SGs were formed in infected cells upon infection with a mutant influenza virus lacking functional NS1 (del NS1) protein, and DDX3 colocalized with NP in SGs. We further determined that the DDX3 helicase domain did not interact with NS1 and NP; however, it was essential for DDX3 localization in virus-induced SGs. Knockdown of DDX3 resulted in impaired SG formation and led to increased virus titers. Taken together, our results identified DDX3 as an antiviral protein with a role in virus-induced SG formation.IMPORTANCEDDX3 is a multifunctional RNA helicase and has been reported to be involved in regulating various virus life cycles. However, its function during influenza A virus infection remains unknown. In this study, we demonstrated that DDX3 is capable of interacting with influenza virus NS1 and NP proteins; DDX3 and NP colocalize in the del NS1 virus-induced SGs. Furthermore, knockdown of DDX3 impaired SG formation and led to a decreased virus titer. Thus, we provided evidence that DDX3 is an antiviral protein during influenza virus infection and its antiviral activity is through regulation of SG formation. Our findings provide knowledge about the function of DDX3 in the influenza virus life cycle and information for future work on manipulating the SG pathway and its components to fight influenza virus infection.

scholarly journals Influenza A Virus NS1 Protein Prevents Activation of NF-κB and Induction of Alpha/Beta Interferon

2000 ◽  
Vol 74 (24) ◽  
pp. 11566-11573 ◽  
Author(s):  
Xiuyan Wang ◽  
Ming Li ◽  
Hongyong Zheng ◽  
Thomas Muster ◽  
Peter Palese ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Wild Type Virus ◽  
Ns1 Protein ◽  
Wild Type ◽  
Functional Link ◽  
Beta Interferon ◽  
Alpha Beta

ABSTRACT The alpha/beta interferon (IFN-α/β) system represents one of the first lines of defense against virus infections. As a result, most viruses encode IFN antagonistic factors which enhance viral replication in their hosts. We have previously shown that a recombinant influenza A virus lacking the NS1 gene (delNS1) only replicates efficiently in IFN-α/β-deficient systems. Consistent with this observation, we found that infection of tissue culture cells with delNS1 virus, but not with wild-type influenza A virus, induced high levels of mRNA synthesis from IFN-α/β genes, including IFN-β. It is known that transactivation of the IFN-β promoter depends on NF-κB and several other transcription factors. Interestingly, cells infected with delNS1 virus showed high levels of NF-κB activation compared with those infected with wild-type virus. Expression of dominant-negative inhibitors of the NF-κB pathway during delNS1 virus infection prevented the transactivation of the IFN-β promoter, demonstrating a functional link between NF-κB activation and IFN-α/β synthesis in delNS1 virus-infected cells. Moreover, expression of the NS1 protein prevented virus- and/or double-stranded RNA (dsRNA)-mediated activation of the NF-κB pathway and of IFN-β synthesis. This inhibitory property of the NS1 protein of influenza A virus was dependent on its ability to bind dsRNA, supporting a model in which binding of NS1 to dsRNA generated during influenza virus infection prevents the activation of the IFN system. NS1-mediated inhibition of the NF-κB pathway may thus play a key role in the pathogenesis of influenza A virus.

scholarly journals Human Staufen1 Protein Interacts with Influenza Virus Ribonucleoproteins and Is Required for Efficient Virus Multiplication

2010 ◽  
Vol 84 (15) ◽  
pp. 7603-7612 ◽  
Author(s):  
Susana de Lucas ◽  
Joan Peredo ◽  
Rosa María Marión ◽  
Carmen Sánchez ◽  
Juan Ortín
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Particle Production ◽  
Nonstructural Protein ◽  
A549 Cells ◽  
Influenza Virus Infection ◽  
Ns1 Protein ◽  
Infected Cells

ABSTRACT The influenza A virus genome consists of 8 negative-stranded RNA segments. NS1 is a nonstructural protein that participates in different steps of the virus infectious cycle, including transcription, replication, and morphogenesis, and acts as a virulence factor. Human Staufen1 (hStau1), a protein involved in the transport and regulated translation of cellular mRNAs, was previously identified as a NS1-interacting factor. To investigate the possible role of hStau1 in the influenza virus infection, we characterized the composition of hStau1-containing granules isolated from virus-infected cells. Viral NS1 protein and ribonucleoproteins (RNPs) were identified in these complexes by Western blotting, and viral mRNAs and viral RNAs (vRNAs) were detected by reverse transcription (RT)-PCR. Also, colocalization of hStau1 with NS1, nucleoprotein (NP), and PA in the cytosol of virus-infected cells was shown by immunofluorescence. To analyze the role of hStau1 in the infection, we downregulated its expression by gene silencing. Human HEK293T cells or A549 cells were silenced using either short hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) targeting four independent sites in the hStau1 mRNA. The yield of influenza virus was reduced 5 to 10 times in the various hStau1-silenced cells compared to that in control silenced cells. The expression levels of viral proteins and their nucleocytoplasmic localization were not affected upon hStau1 silencing, but virus particle production, as determined by purification of virions from supernatants, was reduced. These results indicate a role for hStau1 in late events of the influenza virus infection, possibly during virus morphogenesis.

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