Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is evidence that the nucleoprotein (NP) gene of the classical swine virus (A/Swine/1976/31) clusters with the early human strains at the nucleotide sequence level, while at the level of the amino acid sequence, as defined by consensus amino acids and in functional tests, its NP is clearly "avian like." Therefore it was suggested that the Sw/31 NP had been recently under strong selection pressure, possibly caused by reassortment with other avian influenza genes, whose gene products have to cooperate intimately with NP (Gammelin et al., 1989. Virology 170, 71-80). This suggestion has been investigated by sequencing the genes of internal and nonstructural proteins of Sw/31. The data on these sequences and on the phylogenetic trees are not in accordance with that suggestion: all these genes cluster with the early human strains at the nucleotide level while, at the level of the amino acid sequence, most of them are more closely related to the avian strains, thus resembling NP in this respect. This indicates that these genes rather evolved concomitantly with the NP gene. Our data are in agreement with the suggestion that, at about the time of the Spanish Flu (1918/19), a human influenza A (H1N1) virus entered the pig population. Furthermore, it is known that the NP of the human influenza A viruses--in contrast to that of the avian and swine strains--has been under strong selection pressure to change (Gammelin et al., 1990. Mol. Biol. Evol. 7, 194-200. Gorman et al., 1990a. J. Virol. 64, 1487-1497). Thus, after transfer of a human strain into pigs, the selection pressure might be released, enabling the NP and the other genes of the swine virus to evolve back to the optimal avian sequences, especially at the functionally important consensus positions. The swine influenza viruses circulating since 1979 in Northern Europe--represented by A/Swine/Germany/2/81 (H1N1)--have all genes, so far examined, derived from an avian influenza virus pool and are different from the classical swine viruses.
 ...
PMID:Evolution of pig influenza viruses. 205 97

A series of reassortants has been constructed by crossing of UV-inactivated avian influenza virus of H3N8 subtype and live human influenza virus of H1N1 subtype, adapted to growth in continuous canine kidney cell line (MDCK). The analysis of RNA duplexes has shown that the reassortants contain HA gene of avian influenza virus whereas the other genes belong to human parent virus. The reassortants were efficiently reproduced in MDCK cells at low temperature (limiting for the avian parent virus). The data suggest that the avian virus HA gene does not hamper the reproduction of reassortant viruses in mammalian cells under the conditions unfavorable for the multiplication of avian influenza subtype H3N8 viruses.
Mol Gen Mikrobiol Virusol 1988 Apr
PMID:[Properties of reassortants of human and avian influenza viruses. Reproduction in MDCK cells at suboptimum temperatures]. 340 32

Avian species, particularly waterfowl, are the natural hosts of influenza A viruses. Influenza viruses bearing each of the 15 hemagglutinin and nine neuraminidase subtypes infect birds and serve as a reservoir from which influenza viruses or genes are introduced into the human population. Viruses with novel hemagglutinin genes derived from avian influenza viruses, with or without other accompanying avian influenza virus genes, have the potential for pandemic spread when the human population lacks protective immunity against the new hemagglutinin. Avian influenza viruses were thought to be limited in their ability to directly infect humans until 1997, when 18 human infections with avian influenza H5N1 viruses occurred in Hong Kong. In 1999, two human infections with avian influenza H9N2 viruses were also identified in Hong Kong. These events established that avian viruses could infect humans without acquiring human influenza genes by reassortment in an intermediate host and highlighted challenges associated with the detection of human immune responses to avian influenza viruses and the development of appropriate vaccines.
Cell Mol Life Sci 2000 Nov
PMID:Avian influenza viruses infecting humans. 1113 Jan 81

The analysis of escape mutants of the avian influenza virus of H5 subtype (strain A/Mallard/Pennsylvania/10218/84) revealed the location and structure of two antigenic sites in the hemagglutinin (HA) molecule. Several escape mutants exhibited unusual features in the reactions with monoclonal antibodies (Mabs), being completely resistant in the infectivity neutralization test to the Mabs used for their selection, and retaining the ability to bind the Mabs as revealed by enzyme-linked immunosorbent assay. An enhancement of the binding by an amino acid change in a different antigenic site was demonstrated, as well as a complete abolishment of the binding by a mutation selected by passage in the presence of an excess of the non-neutralizing Mab of high binding ability. The observed effects did not result from the changes in the affinity of the mutant HA toward sialic receptors. The data suggest that one amino acid change in HA may prevent the virus neutralization by different mechanisms for different Mabs: either the binding of the Mab to HA is prevented, or the bound Mab is unable to block the receptor-binding pocket of HA. Different mechanisms of the acquisition of resistance to Mabs in the course of the selection of escape mutants are discussed.
Mol Gen Mikrobiol Virusol 2003
PMID:[Antigenic structure of influenza A virus subtype H5 hemagglutinin: mechanism of acquiring stability to monoclonal antibodies in escape-mutants]. 1265 46

Pigs can be infected with both human and avian influenza A virus (IAV) strains and are therefore considered to be important intermediates in the emergence of new IAV strains due to mixing of viral genes derived from human, avian, or porcine influenza viruses. These reassortant strains may have potential to cause pandemic influenza outbreaks in humans. The innate immune response against IAV plays a significant role in containment of IAV in the airways. We studied the interactions of IAV with porcine surfactant protein D (pSP-D), an important component of this first line defense system. Hemagglutination inhibition analysis shows that the distinct interactions of pSP-D with IAV mediated by the N-linked carbohydrate moiety in the carbohydrate recognition domain of pSP-D depend on the terminal sialic acids (SAs) present on this carbohydrate. Analysis by both lectin staining and by cleavage with linkage-specific sialidases shows that the carbohydrate of pSP-D is exclusively sialylated with alpha(2,6)-linked SAs, in contrast to surfactant protein A, which contains both alpha(2,3)- and alpha(2,6)-linked SAs on its N-linked carbohydrate. Enzymatic modification of the SA-linkages present on pSP-D demonstrates that the type of SA-linkage is important for its hemagglutination-inhibitory activity, and correlates with receptor-binding specificity of the IAV strains. The SAs present on pSP-D appear especially important for interactions with poorly glycosylated IAV strains. It remains to be elucidated to what extent the unique sialylation profile of pSP-D is involved in host range control of IAV in pigs, and whether it facilitates adaptation of avian or human IAV strains that can contribute to the production of reassortant strains in pigs.
Am J Respir Cell Mol Biol 2004 Jun
PMID:Interactions of influenza A virus with sialic acids present on porcine surfactant protein D. 1467 16

Current WHO reports on the Asian avian influenza virus outbreaks are poignant reminders of the potential for the emergence of highly virulent strains of influenza A virus (IAV) and the fact that it remains a scourge on human health. As IAV drifts and shifts its genetic and antigenic composition, it presents an ever-changing challenge for vaccines and antiviral medications. Short-interfering RNAs (siRNAs) are the latest class of potential antiviral therapeutics to be developed. Recent reports using siRNAs in mice suggest that they hold great promise for the prevention and treatment of IAV infections.
Trends Mol Med 2004 Dec
PMID:The promise of siRNAs for the treatment of influenza. 1556 23

In this report, the cDNA sequences of Shaoxing (SX) and Muscovy (MV) duck IL-2 were cloned, then recombinant duck IL-2 (rduIL-2) was produced in prokaryotic expression system. In vitro bioactivity of rduIL-2 was determined by lymphocyte proliferation assay and in vivo bioactivity of rduIL-2 was assessed by vaccine immunization. Monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs) specific for rduIL-2 were generated and characterized by ELISA, Western blot and neutralizing assays. The cDNA contains an open reading frame (ORF) of 420-base pairs encoding a protein of 140 amino acids (aa) with a putative signal peptide of 21aa. The His-duIL-2 fusion protein was recognized in Western blot by mAb against chicken IL-2 (chIL-2), but not by mAbs against human IL-2 and mouse IL-2. Recombinant duIL-2 induces in vitro proliferation of Con A-stimulated duck splenocytes in MTT assay and strengthens duck immune responses induced by vaccinating the inactivated oil emulsion vaccine against avian influenza virus. Polyclonal antibodies and mAb 2B3 against rduIL-2 were shown to have effective neutralizing ability by inhibiting the biological activities of both recombinant duIL-2 and endogenous duIL-2. Despite the fact that duck and chicken IL-2s only share identity of 55.0-56.7% in amino acid sequence, duck and chicken IL-2 molecules displayed similar cross-priming activity in in vitro lymphocyte proliferation assays. The results, at the first time, indicated that rduIL-2 has the potential to be used as an immunoadjuvant for enhancing vaccine efficacy and an immunotherapeutic, and the mAbs against rduIL-2 further facilitate basic immunobiological studies of the role of IL-2 in avian immune system.
Mol Immunol 2005 Mar
PMID:Cloning, in vitro expression and bioactivity of duck interleukin-2. 1560 18

To generate monoclonal anti-idiotypic antibodies (mAb2) against avian influenza virus subtype H9 (H9 AIV), BALB/c mice were immunized with purified chicken anti-H9-AIV IgG and the splenocytes of immunized mice were fused with myeloma cells NS-1. Hybridoma cells were screened by indirect enzyme-linked immunosorbent assays with both chicken and rabbit anti-H9-AIV IgG as coating antigens. One hybridoma cell clone secreting monoclonal antibody against idiotypes shared by both chicken and rabbit anti-H9-AIV IgG was established. Experiments demonstrated the mAb2 was able to inhibit the binding of hemagglutinin to anti-H9-AIV IgG and to induce chickens to generate hemagglutination inhibition antibodies, indicating this anti-species-sharing-idiotypic antibody bore the internal image of hemagglutinin on avian influenza virus.
Cell Mol Immunol 2005 Apr
PMID:Preparation of anti-idiotypic antibody against avian influenza virus subtype H9. 1619 24

Influenza A virus specificity for the host is mediated by the viral surface glycoprotein hemagglutinin (HA), which binds to receptors containing glycans with terminal sialic acids. Avian viruses preferentially bind to alpha2-3-linked sialic acids on receptors of intestinal epithelial cells, whereas human viruses are specific for the alpha2-6 linkage on epithelial cells of the lungs and upper respiratory tract. To define the receptor preferences of a number of human and avian H1 and H3 viruses, including the 1918 H1N1 pandemic strains, their hemagglutinins were analyzed using a recently described glycan array. The array, which contains 200 carbohydrates and glycoproteins, not only revealed clear differentiation of receptor preferences for alpha2-3 and/or alpha2-6 sialic acid linkage, but could also detect fine differences in HA specificity, such as preferences for fucosylation, sulfation and sialylation at positions 2 (Gal) and 3 (GlcNAc, GalNAc) of the terminal trisaccharide. For the two 1918 HA variants, the South Carolina (SC) HA (with Asp190, Asp225) bound exclusively alpha2-6 receptors, while the New York (NY) variant, which differed only by one residue (Gly225), had mixed alpha2-6/alpha2-3 specificity, especially for sulfated oligosaccharides. Only one mutation of the NY variant (Asp190Glu) was sufficient to revert the HA receptor preference to that of classical avian strains. Thus, the species barrier, as defined by the receptor specificity preferences of 1918 human viruses compared to likely avian virus progenitors, can be circumvented by changes at only two positions in the HA receptor binding site. The glycan array thus provides highly detailed profiles of influenza receptor specificity that can be used to map the evolution of new human pathogenic strains, such as the H5N1 avian influenza.
J Mol Biol 2006 Feb 03
PMID:Glycan microarray analysis of the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities. 1634 33

Rapid elucidation of neutralizing antibody epitopes on emerging viral pathogens like severe acute respiratory syndrome (SARS) coronavirus (CoV) or highly pathogenic avian influenza H5N1 virus is of great importance for rational design of vaccines against these viruses. Here we combined screening of phage display random peptide libraries with a unique computer algorithm "Mapitope" to identify the discontinuous epitope of 80R, a potent neutralizing human anti-SARS monoclonal antibody against the spike protein. Using two different types of random peptide libraries which display cysteine-constrained loops or linear 13-15-mer peptides, independent panels containing 42 and 18 peptides were isolated, respectively. These peptides, which had no apparent homologous motif within or between the peptide pools and spike protein, were deconvoluted into amino acid pairs (AAPs) by Mapitope and the statistically significant pairs (SSPs) were defined. Mapitope analysis of the peptides was first performed on a theoretical model of the spike and later on the genuine crystal structure. Three clusters (A, B and C) were predicted on both structures with remarkable overlap. Cluster A ranked the highest in the algorithm in both models and coincided well with the sites of spike protein that are in contact with the receptor, consistent with the observation that 80R functions as a potent entry inhibitor. This study demonstrates that by using this novel strategy one can rapidly predict and identify a neutralizing antibody epitope, even in the absence of the crystal structure of its target protein.
J Mol Biol 2006 May 26
PMID:Mapping a neutralizing epitope on the SARS coronavirus spike protein: computational prediction based on affinity-selected peptides. 1663 Jun 34


1 2 3 4 5 6 7 8 9 10 Next >>