Host cell interactome of PA protein of H5N1 influenza A virus in chicken cells

2016 ◽  
Vol 136 ◽  
pp. 48-54 ◽  
Author(s):  
Qiao Wang ◽  
Qinghe Li ◽  
Ranran Liu ◽  
Maiqing Zheng ◽  
Jie Wen ◽  
...  
Keyword(s):  
Host Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
H5n1 Influenza

Host cell interactome of PB1 N40 protein of H5N1 influenza A virus in chicken cells

2019 ◽  
Vol 197 ◽  
pp. 34-41 ◽  
Author(s):  
Qiao Wang ◽  
Ranran Liu ◽  
Qinghe Li ◽  
Fei Wang ◽  
Bo Zhu ◽  
...  
Keyword(s):  
Host Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
H5n1 Influenza

scholarly journals Effect on Virulence and Pathogenicity of H5N1 Influenza A Virus through Truncations of NS1 eIF4GI Binding Domain

2010 ◽  
Vol 202 (9) ◽  
pp. 1338-1346 ◽  
Author(s):  
Hongbo Zhou ◽  
Jiping Zhu ◽  
Jiagang Tu ◽  
Wei Zou ◽  
Yong Hu ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Binding Domain ◽  
H5n1 Influenza

scholarly journals Characterization of a Human H5N1 Influenza A Virus Isolated in 2003

2005 ◽  
Vol 79 (15) ◽  
pp. 9926-9932 ◽  
Author(s):  
Kyoko Shinya ◽  
Masato Hatta ◽  
Shinya Yamada ◽  
Ayato Takada ◽  
Shinji Watanabe ◽  
...  
Keyword(s):  
Hong Kong ◽  
Avian Influenza ◽  
Influenza A Virus ◽  
Influenza A ◽  
Mainland China ◽  
Virus Infections ◽  
Influenza A Viruses ◽  
H5n1 Avian Influenza Virus ◽  
H5n1 Influenza ◽  
Avian Influenza A Virus

ABSTRACT In 2003, H5N1 avian influenza virus infections were diagnosed in two Hong Kong residents who had visited the Fujian province in mainland China, affording us the opportunity to characterize one of the viral isolates, A/Hong Kong/213/03 (HK213; H5N1). In contrast to H5N1 viruses isolated from humans during the 1997 outbreak in Hong Kong, HK213 retained several features of aquatic bird viruses, including the lack of a deletion in the neuraminidase stalk and the absence of additional oligosaccharide chains at the globular head of the hemagglutinin molecule. It demonstrated weak pathogenicity in mice and ferrets but caused lethal infection in chickens. The original isolate failed to produce disease in ducks but became more pathogenic after five passages. Taken together, these findings portray the HK213 isolate as an aquatic avian influenza A virus without the molecular changes associated with the replication of H5N1 avian viruses in land-based poultry such as chickens. This case challenges the view that adaptation to land-based poultry is a prerequisite for the replication of aquatic avian influenza A viruses in humans.

scholarly journals Suppression of influenza A virus replication in human lung epithelial cells by noncytotoxic concentrations bafilomycin A1

2015 ◽  
Vol 308 (3) ◽  
pp. L270-L286 ◽  
Author(s):  
Behzad Yeganeh ◽  
Saeid Ghavami ◽  
Andrea L. Kroeker ◽  
Thomas H. Mahood ◽  
Gerald L. Stelmack ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Host Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
Life Cycles ◽  
Host Cells ◽  
Nuclear Accumulation ◽  
Low Concentration ◽  
High Concentrations ◽  
The Impact

Subcellular trafficking within host cells plays a critical role in viral life cycles, including influenza A virus (IAV). Thus targeting relevant subcellular compartments holds promise for effective intervention to control the impact of influenza infection. Bafilomycin A1(Baf-A1), when used at relative high concentrations (≥10 nM), inhibits vacuolar ATPase (V-ATPase) and reduces endosome acidification and lysosome number, thus inhibiting IAV replication but promoting host cell cytotoxicity. We tested the hypothesis that much lower doses of Baf-A1also have anti-IAV activity, but without toxic effects. Thus we assessed the antiviral activity of Baf-A1at different concentrations (0.1–100 nM) in human alveolar epithelial cells (A549) infected with IAV strain A/PR/8/34 virus (H1N1). Infected and mock-infected cells pre- and cotreated with Baf-A1were harvested 0–24 h postinfection and analyzed by immunoblotting, immunofluorescence, and confocal and electron microscopy. We found that Baf-A1had disparate concentration-dependent effects on subcellular organelles and suppressed affected IAV replication. At concentrations ≥10 nM Baf-A1inhibited acid lysosome formation, which resulted in greatly reduced IAV replication and release. Notably, at a very low concentration of 0.1 nM that is insufficient to reduce lysosome number, Baf-A1retained the capacity to significantly impair IAV nuclear accumulation as well as IAV replication and release. In contrast to the effects of high concentrations of Baf-A1, very low concentrations did not exhibit cytotoxic effects or induce apoptotic cell death, based on morphological and FACS analyses. In conclusion, our results reveal that low-concentration Baf-A1is an effective inhibitor of IAV replication, without impacting host cell viability.

scholarly journals The human H5N1 influenza A virus polymerase complex is active in vitro over a broad range of temperatures, in contrast to the WSN complex, and this property can be attributed to the PB2 subunit

2008 ◽  
Vol 89 (12) ◽  
pp. 2923-2932 ◽  
Author(s):  
Birgit G. Bradel-Tretheway ◽  
Z. Kelley ◽  
Shikha Chakraborty-Sett ◽  
Toru Takimoto ◽  
Baek Kim ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Influenza A Virus ◽  
Influenza A ◽  
Elevated Temperatures ◽  
Expression System ◽  
Lung Epithelial Cells ◽  
Upper Respiratory Tract ◽  
Polymerase Complex ◽  
H5n1 Influenza

Influenza A virus (IAV) replicates in the upper respiratory tract of humans at 33 °C and in the intestinal tract of birds at close to 41 °C. The viral RNA polymerase complex comprises three subunits (PA, PB1 and PB2) and plays an important role in host adaptation. We therefore developed an in vitro system to examine the temperature sensitivity of IAV RNA polymerase complexes from different origins. Complexes were prepared from human lung epithelial cells (A549) using a novel adenoviral expression system. Affinity-purified complexes were generated that contained either all three subunits (PA/PB1/PB2) from the A/Viet/1203/04 H5N1 virus (H/H/H) or the A/WSN/33 H1N1 strain (W/W/W). We also prepared chimeric complexes in which the PB2 subunit was exchanged (H/H/W, W/W/H) or substituted with an avian PB2 from the A/chicken/Nanchang/3-120/01 H3N2 strain (W/W/N). All complexes were functional in transcription, cap-binding and endonucleolytic activity. Complexes containing the H5N1 or Nanchang PB2 protein retained transcriptional activity over a broad temperature range (30–42 °C). In contrast, complexes containing the WSN PB2 protein lost activity at elevated temperatures (39 °C or higher). The E627K mutation in the avian PB2 was not required for this effect. Finally, the avian PB2 subunit was shown to confer enhanced stability to the WSN 3P complex. These results show that PB2 plays an important role in regulating the temperature optimum for IAV RNA polymerase activity, possibly due to effects on the functional stability of the 3P complex.

scholarly journals Mutation of Influenza A Virus PA-X Decreases Pathogenicity in Chicken Embryos and Can Increase the Yield of Reassortant Candidate Vaccine Viruses

2018 ◽  
Vol 93 (2) ◽  
Author(s):  
Saira Hussain ◽  
Matthew L. Turnbull ◽  
Helen M. Wise ◽  
Brett W. Jagger ◽  
Philippa M. Beard ◽  
...  
Keyword(s):  
Host Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
Control Measure ◽  
Virus Titer ◽  
Virus Antigen ◽  
Economic Consequences ◽  
Primary Control ◽  
X Protein ◽  
X Gene

ABSTRACTThe PA-X protein of influenza A virus has roles in host cell shutoff and viral pathogenesis. While most strains are predicted to encode PA-X, strain-dependent variations in activity have been noted. We found that PA-X protein from the A/PR/8/34 (PR8) strain had significantly lower repressive activity against cellular gene expression than PA-X proteins from the avian strains A/turkey/England/50-92/91 (H5N1) (T/E) and A/chicken/Rostock/34 (H7N1). Loss of normal PA-X expression, either by mutation of the frameshift site or by truncating the X open reading frame (ORF), had little effect on the infectious virus titer of PR8 or PR8 7:1 reassortants with T/E segment 3 grown in embryonated hens’ eggs. However, in both virus backgrounds, mutation of PA-X led to decreased embryo mortality and lower overall pathology, effects that were more pronounced in the PR8 strain than in the T/E reassortant, despite the low shutoff activity of the PR8 PA-X. Purified PA-X mutant virus particles displayed an increased ratio of hemagglutinin (HA) to nucleoprotein (NP) and M1 compared to values for their wild-type (WT) counterparts, suggesting altered virion composition. When the PA-X gene was mutated in the background of poorly growing PR8 6:2 vaccine reassortant analogues containing the HA and neuraminidase (NA) segments from H1N1 2009 pandemic viruses or from an avian H7N3 strain, HA yield increased up to 2-fold. This suggests that the PR8 PA-X protein may harbor a function unrelated to host cell shutoff and that disruption of the PA-X gene has the potential to improve the HA yield of vaccine viruses.IMPORTANCEInfluenza A virus is a widespread pathogen that affects both humans and a variety of animal species, causing regular epidemics and sporadic pandemics, with major public health and economic consequences. A better understanding of virus biology is therefore important. The primary control measure is vaccination, which for humans mostly relies on antigens produced in eggs from PR8-based viruses bearing the glycoprotein genes of interest. However, not all reassortants replicate well enough to supply sufficient virus antigen for demand. The significance of our research lies in identifying that mutation of the PA-X gene in the PR8 strain of virus can improve antigen yield, potentially by decreasing the pathogenicity of the virus in embryonated eggs.

Influenza A virus uses the aggresome processing machinery for host cell entry

Science ◽  
2014 ◽  
Vol 346 (6208) ◽  
pp. 473-477 ◽  
Author(s):  
Indranil Banerjee ◽  
Yasuyuki Miyake ◽  
Samuel Philip Nobs ◽  
Christoph Schneider ◽  
Peter Horvath ◽  
...  
Keyword(s):  
Host Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
Cell Entry ◽  
Processing Machinery ◽  
Host Cell Entry
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