Non-structural protein 1 of avian influenza A viruses differentially inhibit NF-κB promoter activation

<p>Abstract</p> <p>Background</p> <p>Influenza virus infection activates NF-κB and is a general prerequisite for a productive influenza virus infection. On the other hand, non-structural protein 1 (NS1) suppresses this viral activated NF-κB, presumably to prevent expression of NF-κB mediated anti-viral response. NS1 proteins of influenza A viruses are divided into two groups, known as allele A and allele B. The possible functional relevance of this NS1 division to viral pathogenicity is lacking.</p> <p>Findings</p> <p>The ability of NS1 protein from two avian influenza subtypes, H6N8 and H4N6, to inhibit NF-κB promoter activation was assessed. Further, efforts were made to characterize the genetic basis of this inhibition. We found that allele A NS1 proteins of H6N8 and H4N6 are significantly better in preventing dsRNA induced NF-κB promoter activation compared to allele B of corresponding subtypes, in a species independent manner. Furthermore, the ability to suppress NF-κB promoter activation was mapped to the effector domain while the RNA binding domain alone was unable to suppress this activation. Chimeric NS1 proteins containing either RNA binding domain of allele A and effector domain of allele B or vice versa, were equally potent in preventing NF-κB promoter activation compared to their wt. NS1 protein of allele A and B from both subtypes expressed efficiently as detected by Western blotting and predominantly localized in the nucleus in both A549 and MiLu cells as shown by <it>in situ </it>PLA.</p> <p>Conclusions</p> <p>Here, we present another aspect of NS1 protein in inhibiting dsRNA induced NF-κB activation in an allele dependent manner. This suggests a possible correlation with the virus's pathogenic potential.</p

Differences in the ability to suppress interferon β production between allele A and allele B NS1 proteins from H10 influenza A viruses

BACKGROUND: In our previous study concerning the genetic relationship among H10 avian influenza viruses with different pathogenicity in mink (Mustela vison), we found that these differences were related to amino acid variations in the NS1 protein. In this study, we extend our previous work to further investigate the effect of the NS1 from different gene pools on type I IFN promoter activity, the production of IFN-β, as well as the expression of the IFN-β mRNA in response to poly I:C. RESULTS: Using a model system, we first demonstrated that NS1 from A/mink/Sweden/84 (H10N4) (allele A) could suppress an interferon-stimulated response element (ISRE) reporter system to about 85%. The other NS1 (allele B), from A/chicken/Germany/N/49 (H10N7), was also able to suppress the reporter system, but only to about 20%. The differences in the abilities of the two NS1s from different alleles to suppress the ISRE reporter system were clearly reflected by the protein and mRNA expressions of IFN-β as shown by ELISA and RT-PCR assays. CONCLUSIONS: These studies reveal that different non-structural protein 1 (NS1) of influenza viruses, one from allele A and another from allele B, show different abilities to suppress the type I interferon β expression. It has been hypothesised that some of the differences in the different abilities of the alleles to suppress ISRE were because of the interactions and inhibitions at later stages from the IFN receptor, such as the JAK/STAT pathway. This might reflect the additional effects of the immune evasion potential of different NS1s

Full genome comparison and characterization of avian H10 viruses with different pathogenicity in Mink (Mustela vison) reveals genetic and functional differences in the non-structural gene

<p>Abstract</p> <p>Background</p> <p>The unique property of some avian H10 viruses, particularly the ability to cause severe disease in mink without prior adaptation, enabled our study. Coupled with previous experimental data and genetic characterization here we tried to investigate the possible influence of different genes on the virulence of these H10 avian influenza viruses in mink.</p> <p>Results</p> <p>Phylogenetic analysis revealed a close relationship between the viruses studied. Our study also showed that there are no genetic differences in receptor specificity or the cleavability of the haemagglutinin proteins of these viruses regardless of whether they are of low or high pathogenicity in mink.</p> <p>In poly I:C stimulated mink lung cells the NS1 protein of influenza A virus showing high pathogenicity in mink down regulated the type I interferon promoter activity to a greater extent than the NS1 protein of the virus showing low pathogenicity in mink.</p> <p>Conclusions</p> <p>Differences in pathogenicity and virulence in mink between these strains could be related to clear amino acid differences in the non structural 1 (NS1) protein. The NS gene of mink/84 appears to have contributed to the virulence of the virus in mink by helping the virus evade the innate immune responses.</p

Metapopulation Dynamics Enable Persistence of Influenza A, Including A/H5N1, in Poultry

Thanks to K. Sturm-Ramirez, C. Jessup, J. Rosenthal and the staff of EcoHealth Alliance for feedback. Disclaimer: The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government.Conceived and designed the experiments: PRH TF RH DZ CSA AG MJM XX TB PD. Performed the experiments: PRH. Analyzed the data: PRH. Contributed reagents/materials/analysis tools: PRH TF RH DZ CSA AG MJM XX TB JHJ PD. Wrote the paper: PRH TF RH DZ CSA AG MJM XX TB JHJ PD.Highly pathogenic influenza A/H5N1 has persistently but sporadically caused human illness and death since 1997. Yet it is still unclear how this pathogen is able to persist globally. While wild birds seem to be a genetic reservoir for influenza A, they do not seem to be the main source of human illness. Here, we highlight the role that domestic poultry may play in maintaining A/H5N1 globally, using theoretical models of spatial population structure in poultry populations. We find that a metapopulation of moderately sized poultry flocks can sustain the pathogen in a finite poultry population for over two years. Our results suggest that it is possible that moderately intensive backyard farms could sustain the pathogen indefinitely in real systems. This fits a pattern that has been observed from many empirical systems. Rather than just employing standard culling procedures to control the disease, our model suggests ways that poultry production systems may be modified.Yeshttp://www.plosone.org/static/editorial#pee

The Advantages and Shortcomings of Using Nano-sized Energetic Materials

Energetic materials are substances that can store chemical energy in their chemical bonds. An ideal energetic material is a substance with high performance, safety and shelf life. Many recent researches have concentrated on the synthesis or the development of new energetic materials with optimized properties, such as thermal stability, sensitivity and burn rate. The reduction of the particle size of energetic materials from micron to nano-sized is one of the suitable approaches for obtaining desirable properties. Recent progress on the reduction of the particle size of energetic materials is reviewed in this work. The effects of nano-sized particles on the performance of energetic compounds are also investigated

Some High Nitrogen Derivatives of Nitrotetrazolylimidazole as New High Performance Energetic Compounds

This work introduces important properties of some new derivatives of nitrotetrazolyl-imidazole as high nitrogen energetic compounds, which are evaluated and discussed using some reliable models. The predicted properties are also compared with 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (HMX). It is shown that some of these compounds can be seen as interesting organic explosives with relatively high performance and low sensitivity, which could be used for important industrial applications. Since some of the new compounds have a relatively good oxygen balance, the calculated specific impulses confirm that these compounds can be considered as suitable oxidizers in solid propellants

Detection and Phylogenetic Analysis of Peste des Petits Ruminants Virus Isolated from Outbreaks in Punjab, Pakistan

Peste des Petits Ruminants (PPR) is an important viral disease of small ruminants and is endemic in Pakistan. In the following study, samples from two outbreaks of PPR in goats have been subjected to laboratory investigations. The Peste des Petits Ruminants virus (PPRV) genome was detected using both conventional and real-time PCR. Genetic characterization of the local PPRV field isolates was conducted by sequencing 322bp of the fusion (F) gene and 255bp of the nucleoprotein (N) gene. The phylogenetic tree based on the F gene clustered samples from both outbreaks into lineage 4 along with other Asian isolates, specifically into subcluster 1 along with isolates from Middle East. Analysis of N gene revealed a different pattern. In this case, the Pakistani samples clustered with Chinese, Tajikistani and Iranian isolates, which probably represents the true geographical pattern of virus circulation. This is the first report presenting the phylogenetic tree based on N gene as well as performing a parallel comparison of the trees of F and N gene together from Pakistani isolates. The results of this study shed light on the PPRV population in Pakistan and emphasize the importance of using molecular methods to understand the epidemiology. Such understanding is essential in any efforts to control the number and impact of outbreaks that are occurring in endemic countries such as Pakistan, especially in the current scenario where OIE and FAO are eager to control and subsequently eradicate PPR from the globe, as has been achieved for Rinderpest