Characterization of temperature sensitive influenza virus mutants defective in neuraminidase

Palese, Peter; Tobita, Kiyotake; Ueda, Masahiro; Compans, Richard W.

doi:10.1016/0042-6822(74)90276-1

Cited by 730 publications

(482 citation statements)

References 37 publications

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“…Early in infection it may allow the virus to penetrate mucin layers rich in neuraminic acid, which cover the epithelial cells of the respiratory tract (Burnet, 1948). Late in infection, it has been shown to permit release of progeny virus particles from the host cell and to prevent aggregation (Palese et al, 1974). This concept was further supported by the observation that an NA-minus mutant of influenza virus is still infectious but produces progeny virus only in the presence of exogenously added bacterial NA (Liu & Air, 1993).…”

Section: Introductionsupporting

confidence: 53%

Biosynthesis, intracellular transport and enzymatic activity of an avian influenza A virus neuraminidase: role of unpaired cysteines and individual oligosaccharides.

Hausmann

Kretzschmar

Garten

et al. 1997

Journal of General Virology

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Intracellular transport, glycosylation, tetramerization and enzymatic activity of the neuraminidase (NA) of fowl plague virus (FPV) were analysed in vertebrate cells after expression from a vaccinia virus vector. Tetramerization occurred with a halftime of 15 min, whereas passage through the medial Golgi apparatus and transport to the plasma membrane occurred with half-times of 2 and 3 h, respectively, suggesting a step in NA maturation beyond tetramerization that limits the rate of transport to the medial Golgi. NA transport rates were about fourfold slower than those of haemagglutinin (HA). Slow transport and processing of FPV NA was not altered by coexpression of FPV HA, nor was the transport rate of HA influenced by NA. The slow transport kinetics of NA were also observed in FPVinfected CV-1 cells. As deduced from the coding sequence, FPV NA has the shortest stalk of all naturally occurring NAs described to date and

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Section: Introductionsupporting

confidence: 53%

Biosynthesis, intracellular transport and enzymatic activity of an avian influenza A virus neuraminidase: role of unpaired cysteines and individual oligosaccharides.

Hausmann

Kretzschmar

Garten

et al. 1997

Journal of General Virology

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“…Thus there is no amplification of virus and the infection proceeds no further 101 . NA is described as a receptor destroying enzyme but it has been recognized for many years that some influenza viruses do not elute from agglutinated red blood cells, showing that the NA specificity does not match that of the HA 51 .…”

Section: Role Of Namentioning

confidence: 99%

Influenza neuraminidase

Air

2011

Influenza Resp Viruses

208

216

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Influenza neuraminidase is the target of two licensed antivirals that have been very successful, with several more in development. However, neuraminidase has been largely ignored as a vaccine target despite evidence that inclusion of neuraminidase in the subunit vaccine gives increased protection. This article describes current knowledge on the structure, enzyme activity and antigenic significance of neuraminidase.

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“…The purities of 3061 and 788 were 96% and 95%, respectively. (21). MDCK cells were obtained from American Type Culture Collection and were grown in DMEM (Dulbecco's modified Eagle medium) containing 10% FBS and penicillin-streptomycin at 37°C under 5% CO 2 unless stated otherwise.…”

Section: Methodsmentioning

confidence: 99%

High-throughput identification of compounds targeting influenza RNA-dependent RNA polymerase activity

Cheng

Lin

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

120

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As influenza viruses have developed resistance towards current drugs, new inhibitors that prevent viral replication through different inhibitory mechanisms are useful. In this study, we developed a screening procedure to search for new antiinfluenza inhibitors from 1,200,000 compounds and identified previously reported as well as new antiinfluenza compounds. Several antiinfluenza compounds were inhibitory to the influenza RNA-dependent RNA polymerase (RdRP), including nucleozin and its analogs. The most potent nucleozin analog, 3061 (FA-2), inhibited the replication of the influenza A/WSN/33 (H1N1) virus in MDCK cells at submicromolar concentrations and protected the lethal H1N1 infection of mice. Influenza variants resistant to 3061 (FA-2) were isolated and shown to have the mutation on nucleoprotein (NP) that is distinct from the recently reported resistant mutation of Y289H [Kao R, et al. (2010) Nat Biotechnol 28:600]. Recombinant influenza carrying the Y52H NP is also resistant to 3061 (FA-2), and NP aggregation induced by 3061 (FA-2) was identified as the most likely cause for inhibition. In addition, we identified another antiinfluenza RdRP inhibitor 367 which targets PB1 protein but not NP. A mutant resistant to 367 has H456P mutation at the PB1 protein and both the recombinant influenza and the RdRP expressing the PB1 H456P mutation have elevated resistance to 367. Our high-throughput screening (HTS) campaign thus resulted in the identification of antiinfluenza compounds targeting RdRP activity.high-throughput screening | antiinfluenza | influenza NP | influenza PB1 | chemical genetics

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Characterization of temperature sensitive influenza virus mutants defective in neuraminidase

Cited by 730 publications

References 37 publications

Biosynthesis, intracellular transport and enzymatic activity of an avian influenza A virus neuraminidase: role of unpaired cysteines and individual oligosaccharides.

Biosynthesis, intracellular transport and enzymatic activity of an avian influenza A virus neuraminidase: role of unpaired cysteines and individual oligosaccharides.

Influenza neuraminidase

High-throughput identification of compounds targeting influenza RNA-dependent RNA polymerase activity

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