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Bacteroides fragilis* ; Bacteroides* ; Genetic Structures* ; Neuraminidase*

In annual epidemics and occasional pandemics, influenza viruses cause acute respiratory illnesses in infected humans. Vaccines and antiviral drugs are two main arsenals available for a fight against influenza viruses. However, vaccines often exhibit a limited efficacy in high risk populations, and antiviral drugs are always concerned for mutations, which confer viral resistance. Here we review current advances and knowledge in relation to the usage of antiviral drugs as a prophylactic or therapeutic and the mechanism of resistant variants mainly against the neuraminidase inhibitors. Comprehensive understanding of the resistant mechanism will pave a road for developing new antivirals and/or finding medical or natural alternatives inducing less frequent resistance, and application of combination therapy using two or three different kinds of antivirals can suggest a useful medical intervention against both of seasonal and highly pathogenic influenza viruses including resistant variants. In this review, we provide insights of antiviral drugs for the control and prevention of influenza viruses.
Antiviral Agents ; Humans ; Influenza, Human ; Neuraminidase ; Orthomyxoviridae ; Pandemics ; Seasons ; Vaccines

During our ongoing investigation of neuraminidase inhibitors from medicinal fungi, we found that the fruiting bodies of Phellinus igniarius exhibited significant inhibitory activity against neuraminidase from recombinant H3N2 influenza viruses. Two active compounds were isolated from the methanolic extract of P. igniarius through solvent partitioning and Sephadex LH-20 column chromatography. The active compounds were identified as phelligridins E and G on proton nuclear magnetic resonance (¹H NMR) and electrospray ionization mass measurements. These compounds inhibited neuraminidases from recombinant rvH1N1, H3N2, and H5N1 influenza viruses, with IC₅₀ values in the range of 0.7~8.1 µM.
Chromatography ; Fruit* ; Fungi ; Magnetic Resonance Spectroscopy ; Methanol ; Neuraminidase* ; Orthomyxoviridae ; Protons

Oseltamivir is a potent selective neuraminidase enzyme inhibitor and effective against nearly all strains of influenza A and B. The importance of treating influenza has been recognized, and oseltamivir has been prescribed frequently at the onset of the H1N1 influenza A pandemic this year. However, oseltamivir can cause hemorrhagic colitis as a rare adverse effect. Until now, only two cases of hemorrhagic colitis following the use of oseltamivir have been reported in Japan, and none have been reported in Korea. We report a case of acute hemorrhagic colitis in a 15-year-old boy after the oral administration of oseltamivir for swine originating influenza A.
Administration, Oral ; Adolescent ; Colitis ; Humans ; Influenza, Human ; Japan ; Korea ; Neuraminidase ; Oseltamivir ; Pandemics ; Swine

Twelve nucleotides located at the 3′ end of viral genomic RNA (vRNA) are conserved among influenza A viruses (IAV) and have a promoter function. Hoffmann's 8-plasmid reverse genetics vector system introduced mutations at position 4, C nucleotide (C4) to U nucleotide (U4), of the 3′ ends of neuraminidase (NA) and matrix (M) vRNAs of wild-type A/PR/8/34 (PR8). This resulted in a constellation of C4 and U4 vRNAs coding for low (polymerases) and relatively high (all others) copy number proteins, respectively. U4 has been reported to increase promoter activity in comparison to C4, but the constellation effect on the replication efficiency and pathogenicity of reverse genetics PR8 (rgPR8) has not been fully elucidated. In the present study, we generated 3 recombinant viruses with C4 in the NA and/or M vRNAs and rgPR8 by using reverse genetics and compared their pathobiological traits. The mutant viruses showed lower replication efficiency than rgPR8 due to the low transcription levels of NA and/or M genes. Furthermore, C4 in the NA and/or M vRNAs induced lower PR8 virus pathogenicity in BALB/c mice. The results suggest that the constellation of C4 and U4 among vRNAs may be one of the multigenic determinants of IAV pathogenicity.
Animals ; Clinical Coding ; Influenza A virus ; Influenza, Human* ; Mice ; Neuraminidase* ; Nucleotides ; Orthomyxoviridae* ; Reverse Genetics ; RNA* ; Virulence*

PURPOSE: Nitrocellulose membrane–based filtration system (NCFS) is widely used for protein concentration. In this study, we applied NCFS for production of virus-like particle (VLP) as a vaccine candidate and evaluated yield property and immunogenicity. MATERIALS AND METHODS: Influenza VLPs were generated by baculovirus-insect cell protein expression system. NCFS and sucrose gradient ultracentrifugation were used for purification of VLP. Immunogenicity of VLP was evaluated by animal experiment. RESULTS: Influenza VLPs expressing hemagglutinin (HA) and neuraminidase proteins derived from highly pathogenic influenza virus (H5N8) were effectively produced and purified by NCFS. HA activity of VLP which correlated with antigenicity was well conserved during multiple purification steps. This NCFS based purified VLPs induced influenza virus–specific antibody responses. CONCLUSION: Our results indicate that the influenza VLP vaccine could be prepared by NCFS without loss of immunogenicity and elicit antigen-specific immune responses.
Animal Experimentation ; Antibody Formation ; Baculoviridae ; Collodion* ; Filtration* ; Hemagglutinins ; Influenza, Human* ; Membranes* ; Neuraminidase ; Orthomyxoviridae ; Sucrose ; Ultracentrifugation ; Vaccines

Influenza viruses cause annual epidemics and occasional pandemics that have claimed the millions of lives. On December 4th 2009, more than 207 countries and overseas territories have reported laboratory confirmed cases of pandemic influenza H1N1 2009, which has claimed at least 8768 lives. Up to this date, the pandemic influenza H1N1 2009 has spread throughout the world with unprecedented speed. Accurate and rapid diagnosis of this influenza virus is critical for minimizing further spread, combined with timely implementation of antiviral treatment and public health based measures. Recently, the percentage of oseltamivir-resistant human seasonal H1N1 has increased to 98.5% in USA, and 99.8% in Korea. Fortunately, the pandemic influenza H1N1 2009 is sensitive to neuraminidase inhibitors, including oseltamivir. However, the percentage oseltamivir-resistant pandemic influenza H1N1 2009 is expected to increase with time. In this review, the various diagnostic method and the antiviral agents that have been reported in the literature will be discussed.
Antiviral Agents ; Humans ; Influenza, Human ; Korea ; Neuraminidase ; Orthomyxoviridae ; Oseltamivir ; Pandemics ; Public Health ; Seasons

Cell Line, Tumor ; Genetic Vectors ; Humans ; Male ; Neuraminidase ; genetics ; metabolism ; Prostate ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology

To understand the genetic characteristics of hemagglutinin (HA) and neuraminidase (NA) of type B influenza viruses in Guangzhou in 2006, three virus strains from etiology surveillance and seven strains from outbreaks were investigated. Genome RNAs of type B influenza viruses were extracted and reverse-transcripted into cDNAs using random primers. The whole-length DNA of HA and NA were amplified by polymerase chain reaction (PCR), cloned into T-A plasmid and sequenced, and analyzed phylogenetically by DNAstar software. The results showed that the HA of type B influenza viruses were similar and the homology were more than 99%. The type B influenza viruses belong to Victoria lineage. The NA of the type B influenza viruses were similar and the homology were more than 98%. Phylogenetic trees of HA and NA showed that the isolates from etiology surveillance formed a cluster, and the isolates from outbreaks were separated from the cluster. The homology of the type B influenza viruses with B/Shanghai/361/2002, which is the WHO recommended influenza vaccine strain in 2005-2006, were 88.9%-89.7%. It suggested the protective effect of influenza vaccine against type B influenza viruses used in 2005-2006 in Guangzhou may not be afforded.
China ; Hemagglutinin Glycoproteins, Influenza Virus ; genetics ; Influenza B virus ; genetics ; Neuraminidase ; genetics ; Phylogeny ; Time Factors

The NA genes of 395 strains of human H3N2 influenza virus isolated from 1996 to 2005 in China were sequenced, analyzed with bioinformatics tools. The NA nucleotide sequence of phylogenetic tree showed a main evolution branch with multiple short side branches. The strains in the same year may be divided into several branches. There was an obvious lag between vaccine strains recommended by WHO and the Chinese circulating strains in phylogenetic tree of the NA nucleotide. The result also showed no amino acid deletion and insertion in the NA. In NA antigen sites, where including residues 197-199 aa, 431-434 aa and 339-347aa the mutation was higher, in contrast, the residues including 153 aa, 328-336 aa, 367-370aa and 400-403 aa, the mutation was lower. Besides the antigenic determinant sites, there also had the other amino acid mutated highly, such as 18, 23, 30, 93, 143, 208, 216, 221, 249, 265, 267, 307, 385 and 437 aa, among them 143 and 267 mutation were higher than that in antigenic determinant sites, their biological significance are not clear yet. The neuraminidase active-site residues in NA were highly conservative and the same were the disulphide bond and the glycosylation sites in NA. In conclusion, our analysis provides some information for influenza prevention and control and the NA inhibitor medicine application.
China ; Genes, Viral ; Humans ; Influenza A Virus, H3N2 Subtype ; genetics ; Mutation ; Neuraminidase ; genetics ; Phylogeny ; Time Factors