Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00572 (Asn)
 11,732 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The complete coding region of hemagglutinin genes from 26 influenza A viruses of H9N2 subtype isolated from chicken flocks in China during 1996-2001 was amplified and sequenced. Sequence analysis and phylogenetic studies of H9N2 subtype viruses on the basis of data of 26 viruses in this study and 71 selected strains available in the GenBank were conducted. The results revealed that all the mainland China isolates showed high homology (94.19%-100%) and were assigned to a special sublineage in the major Eurasian lineage, in contrast to the high heterogeneity of Hong Kong SAR isolates. All the 29 mainland China isolates and six Hong Kong SAR strains also had the following common characteristics: sharing the same sequence of proteolytic cleavage site with one additional basic amino acid, RSSR, with only two exceptions; having the same amino acid motif of the receptor-binding site, YWTNV/ALY; 23 of 28 isolates bearing seven potential glycosylation sites and the remaining five having six; and sharing characteristic deduced amino acid residues Asn-183 at the receptor-binding site and Ser-130 at the potential glycosylation site. We concluded that the H9N2 subtype influenza viruses circulating in chicken flocks in China since the 1990s and Ck/HK/G9/97-like viruses isolated in Hong Kong SAR should have a common origin, whereas Qu/HK/G1/97-like viruses including human strains isolated in Hong Kong SAR might originate from other places. The available evidence also suggests that the H9N2 viruses of special lineage themselves and factors prone to secondary infections may contribute to the widespread and dominant distribution of viruses of this subtype in chicken flocks in China and other Asian countries.
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PMID:Phylogenetic analysis of the hemagglutinin genes of twenty-six avian influenza viruses of subtype H9N2 isolated from chickens in China during 1996-2001. 1271 66

Two strains of Influenza B virus were isolated in Vero cells. Subclones with improved efficiency of plaque formation were selected. The activity of the neuraminidase (NA) of the two subclones compared to their respective isolates dropped 20- and 100-fold, respectively. Both subclones had a common mutation in segment 6 leading to a change from Asp to Asn at position 457 in the NA. This mutation destroyed a salt bridge of the contact surface between the monomers, thereby causing the loss in enzymatic activity. The decreased NA activity caused improved plaque formation but had no significant impact on the replication in liquid culture.
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PMID:Effect of a single mutation in neuraminidase on the properties of Influenza B virus isolates. 1468 82

Interactions of the hemagglutinin (HA) of influenza viruses with sialic acids (SA) are important for host range restriction. Most human H3s have a Ser193, while avian and equine H3s usually have an Asn or a Lys, respectively. To investigate the role of residue 193 in the recognition of SA, substitutions were introduced by mutagenesis within a human H3 and an equine H3. Hemadsorption assays performed on COS-1 cells expressing wt or mutated HAs, showed that a K193S substitution in the context of an equine H3 decreased its ability to bind several animal erythrocytes. Using de- and then alpha2,3 or alpha2,6 re-sialylated chicken erythrocytes we showed that for both human and equine H3s, substitution of a Serine by positively-charged Arginine or Lysine at position 193 increased binding to its preferred receptor, SAalpha2,6Gal and SAalpha2,3Gal, respectively. Moreover, when combined with the L194I substitution, the S193R substitution induced binding of the human H3 to NeuAcalpha2,3Gal.
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PMID:Binding of the hemagglutinin from human or equine influenza H3 viruses to the receptor is altered by substitutions at residue 193. 1529 Mar 89

We recently analyzed a series of H5N1 viruses isolated from healthy ducks in southern China since 1999 and found that these viruses had progressively acquired the ability to replicate and cause disease in mice. In the present study, we explored the genetic basis of this change in host range by comparing two of the viruses that are genetically similar but differ in their ability to infect mice and have different pathogenicity in mice. A/duck/Guangxi/22/2001 (DKGX/22) is nonpathogenic in mice, whereas A/duck/Guangxi/35/2001 (DKGX/35) is highly pathogenic. We used reverse genetics to create a series of single-gene recombinants that contained one gene from DKGX/22 and the remaining seven gene segments from DKGX/35. We find that the PA, NA, and NS genes of DKGX/22 could attenuate DKGX/35 virus to some extent, but PB2 of DKGX/22 virus attenuated the DKGX/35 virus dramatically, and an Asn-to-Asp substitution at position 701 of PB2 plays a key role in this function. Conversely, of the recombinant viruses in the DKGX/22 background, only the one that contains the PB2 gene of DKGX/35 was able to replicate in mice. A single amino acid substitution (Asp to Asn) at position 701 of PB2 enabled DKGX/22 to infect and become lethal for mice. These results demonstrate that amino acid Asn 701 of PB2 is one of the important determinants for this avian influenza virus to cross the host species barrier and infect mice, though the replication and lethality of H5N1 influenza viruses involve multiple genes and may result from a constellation of genes. Our findings may help to explain the expansion of the host range and lethality of the H5N1 influenza viruses to humans.
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PMID:Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model. 1614 Jul 81

Inhibition of neuraminidase (NA) activity prevents release of progeny virions from influenza-infected cells and removal of neuraminic (sialic) acid moieties from glycans attached to hemagglutinin (HA). Neuraminic acid moieties situated near the HA receptor-binding site can reduce the efficiency of virus binding and decrease viral dependence on NA activity for replication. With the use of reverse genetics technique, we investigated the effect of glycans attached at Asn 94a, 129, and 163 on the virus susceptibility to NA inhibitors in MDCK cells and demonstrated that the glycan attached at Asn 163 plays a dominant role in compensation for the loss of NA activity.
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PMID:Effect of hemagglutinin glycosylation on influenza virus susceptibility to neuraminidase inhibitors. 1616 Jan 69

Receptor specificity of influenza A/H5 viruses including human 2003-04 isolates was studied. All but two isolates preserved high affinity to Sia2-3Gal (avian-like) receptors. However, two isolates (February, 2003, Hong Kong) demonstrated decreased affinity to Sia2-3Gal and moderate affinity to a Sia2-6Gal (human-like) receptors. These two viruses had a unique Ser227-Asn change in the hemagglutinin molecule. Thus, a single amino acid substitution can significantly alter receptor specificity of avian H5N1 viruses, providing them with an ability to bind to receptors optimal for human influenza viruses. Asian 2003-04 H5 isolates from chickens and humans demonstrated highest affinity to the sulfated trisaccharide Neu5Acalpha2-3Galbeta1-4(6-HSO3)GlcNAcbeta (Su-3'SLN) receptor but, in contrast to 1997 isolates, had increased affinity to fucosylated Su-3'SLN. American poultry H5 viruses also had increased affinity to Su-3'SLN. These data demonstrate that the genetic evolution of avian influenza A(H5N1) viruses is accompanied during adaptation to poultry by the evolution of their receptor specificity.
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PMID:Evolution of the receptor binding phenotype of influenza A (H5) viruses. 1622 89

The susceptibilities of five zanamivir-resistant and six oseltamivir-resistant influenza viruses were assessed against four neuraminidase (NA) inhibitors, including peramivir and A-315675, by a fluorometric NA activity inhibition assay. The enzyme activity of a majority of the variants was effectively inhibited by either A-315675 or both peramivir and A-315675 (50% inhibitory concentration, <10 nM). A novel oseltamivir-resistant influenza virus B variant carrying substitution at residue 198 (Asp-->Asn) (N2 numbering) retained susceptibility to peramivir and A-315675. In vivo, the Asn198 variant showed no apparent fitness impairment as judged by its recovery on day 5 from the nasal washes of ferrets coinfected with equal doses of the wild-type virus and the Asn198 variant. Based on the sequence analysis of the virus in the nasal washes, oseltamivir treatment (5 mg/kg twice daily for 5 days) did not provide growth advantage to the Asn198 variant. Nevertheless, treatment with A-315675 (prodrug A-322278) reduced the number of the animals (two of seven) shedding the Asn198 variant. These studies indicate that different patterns of susceptibility and cross-resistance between NA inhibitors may prove important if antiviral resistance to zanamivir and oseltamivir were to emerge.
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PMID:Susceptibilities of antiviral-resistant influenza viruses to novel neuraminidase inhibitors. 1625 Dec 90

We investigated the frequency of amantadine-resistant influenza A viruses in Nara Prefecture during four epidemic seasons from 2001-02 to 2004-05. Point mutations within the M2 gene were identified using RT-PCR and DNA sequencing analysis. Five viruses (3.4%) with point mutation were observed from 145 strains analyzed. Three viruses (2.0%) possessed a change at position 31 (AGT-->AAT, Ser to Asn), one virus (0.7%) showed a change at position 26 (CTT-->TTT, Leu to Phe), one virus (0.7%) showed a change at position 27 (GTT-->ATT, Val to Ile), and none showed a change at position 30. All of these changes were the transition type of mutation. These results indicated that the possible circulation of drug-resistant viruses to the community was not supported by the findings obtained during the 2004-05 season in Nara.
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PMID:Frequency of amantadine-resistant influenza A virus isolated from 2001-02 to 2004-05 in Nara Prefecture. 1678 5

Using the newly designed mismatch amplification mutation assay (MAMA) PCR, we demonstrated the high frequency of amantadine-resistant influenza A (H3N2) viruses isolated during the 2005-2006 season by detecting the mutation at amino acid position 31 of the M2 protein (S31N). Further, phylogenetic analyses of the HA1 sequences of the S31N viruses revealed that they comprised a clonal lineage that would result in the common characteristic amino acid changes at positions 193 (Ser to Phe) and 225 (Asp to Asn) of the HA protein. We also demonstrated that the S31N/S193F/D225N viruses had already emerged in Aichi Prefecture by the end of the previous 2004-2005 season.
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PMID:High frequency of amantadine-resistant influenza A (H3N2) viruses in the 2005-2006 season and rapid detection of amantadine-resistant influenza A (H3N2) viruses by MAMA-PCR. 1764 34

Mutation in one of five key amino acid residues (positions 26, 27, 30, 31 and 34) within the M2 protein of influenza A viruses, leads to resistance against the adamantane class of anti-influenza drugs. To investigate the emergence and prevalence of adamantane resistance in Alberta, Canada (between 1970 and 2007), 381 influenza A positive samples (original patient specimens) or isolates (virus cultured from patient specimens) were analyzed for changes in these critical amino acid residues. Our results show a significant increase in adamantane resistance in circulating H3N2 viruses in Alberta from 2005 and 2006 when compared with those from 2004 (p<0.001). Adamantane resistance peaked at 74% in 2006 and then decreased (to 38%) in 2007 (p=0.001). All resistant H3N2 viruses contained the substitution Ser to Asn at amino acid position 31 of the M2 protein with two viruses having an additional Ala to Val substitution at position 30. Resistance was not observed in the H1N1 viruses tested. Results presented here are concordant with, and extend, previous reports of increased resistance to adamantanes in Asia and North America in recent years. It is important to continue studies to evaluate circulating influenza A viruses for antiviral resistance markers to ensure their optimal use for prophylaxis and treatment of influenza.
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PMID:Adamantane resistance in circulating human influenza A viruses from Alberta, Canada (1970-2007). 1825 11


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