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Query: UMLS:C0021400 (influenza)
 57,666 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two influenza A viruses whose hemagglutinin (HA) did not react with any of the reference antisera for the 13 recognized HA subtypes were isolated from mallard ducks in the USSR. Antigenic analysis by hemagglutination inhibition and double immunodiffusion tests showed that the HAs of these viruses are similar to each other but distinct from the HAs of other influenza A viruses. Nucleotide sequence analysis showed that these HA genes differ from each other by only 21 nucleotides. However, they differ from all other HA subtypes at the amino acid level by at least 31% in HAI. Thus, we propose that the HAs of these viruses [A/Mallard/Gurjev/263/82 (H14N5) and A/Mallard/Gurjev/244/82 (H14N6) belong to a previously unrecognized subtype, and are designated H14. Unlike any other HAs of influenza viruses, the H14 HAs contained lysine at the cleavage site between HA1 and HA2 instead of arginine. Experimental infection of domestic poultry and ferrets with A/Mallard/Gurjev/263/82 (H14N5) showed that the virus is avirulent for these animals. Based on comparative sequence analysis of different HA genes, it is suggested that differences of 30% or more at the amino acid level in HA1 constitute separate subtypes. Phylogenetic analysis of representatives of each HA subtype showed that H14 is one of the most recently diverged lineages while H8 and H12 branched off early during the evolution of the HA subtypes. These latter two subtypes (H8 and H12) have been isolated very infrequently in recent years, suggesting that these old subtypes may be disappearing from the influenza reservoirs in nature.
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PMID:Molecular characterization of a new hemagglutinin, subtype H14, of influenza A virus. 223 69

Electrophoresis in polyacrylamide gel of the reference influenza A/Victoria/35/72 (H3N2) virus and its persisting variants (PV) showed that the PV isolated on the 158th day from the moment of persistence modelling (PV158) had mutation in the gene of hemagglutinin (HA). This mutation is manifested by incomplete HA synthesis at 40 degrees C and increase of mobility of the light HA subunit (HA2). Analysis of nucleotide sequence of the greater part of HA gene of PV158 virus revealed 5 nucleotide substitutions four of which were significant. Three substitutions were found in Hal: 219 (Ser----Phe), 220 (Arg----Gly), 226 (Leu----Gln) and one in HA2: 156 (Thr----Asn). The importance of these mutations in the determination of the PV phenotype is discussed.
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PMID:[The characteristics of the hemagglutinin from persistent variants of the influenza virus A/Victoria/35/72 (H3N2)]. 226 78

A panel of H-2k class II-restricted T helper (Th) clones were established from individual CBA mice intranasally infected with A/X31 influenza virus. In a study of their fine specificity, it was revealed that recognition of hemagglutinin (HA) by certain Th clones was dependent on conformational features of the molecule. Five HA-specific Th clones failed to recognize X31 mutant viruses R19 and R20 each with a His to Arg substitution at position 17 of HA1. This amino acid substitution affects the conformational stability of the molecule. Each of the 5 clones responded to purified HA but failed to recognize tryptic fragments of HA consisting of HA1 residues 28-328 (tops) and the remainder of the virus including residues 1-27 of HA1 (aggregate). A further 20 HA-specific clones responded to R19 and R20 mutants and to HA1 tops. The R19 and R20 negative clones also showed diminished proliferative responses to pH 5-treated X31. Low pH treatment results in an irreversIble conformational change which affects the integrity of the globular head region of the HA trimer. In addition, four of the five clones failed to recognize variant virus Eng-72 which has Arg to Gly substitution at position 208 in the interface antibody-binding region. This region is antigenically and structurally altered in tops and pH 5-treated X31. The results suggest that recognition of HA by certain Th clones is dependent on the three-dimensional structure of the molecule and that Th cells may recognize conformational determinants in addition to primary structure.
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PMID:Conformational-dependent recognition of influenza virus hemagglutinin by murine T helper clones. 2484 26

A fine specificity analysis of influenza hemagglutinin-specific IAk-restricted T cell clones using natural virus variants of the H3N2 subtype, monoclonal antibody-selected variants and a synthetic peptide corresponding to a variable region of the HA1 polypeptide has provided insight on the structural basis for T cell recognition. A glycine to arginine substitution at HA1 135 abrogates recognition by a panel of T cell clones which, according to their reactivity for natural virus variants, have different antigenic specificities: three clones recognize a synthetic peptide (HA1 residues 118-138) but fail to recognize the monoclonal antibody-selected mutant (Gly135/Arg). There is no correlation, however, between differences in T cell specificity for the natural virus variants and HA1 amino acid sequences in this region. Two further clones have a reduced proliferative response to mutant recognize a completely different spectrum of natural variants, and only one of these clones recognizes the synthetic peptide. We speculate that influenza hemagglutinin employs a common strategy during antigenic drift to evade antibody recognition and effective processing/presentation to subtype-specific T cell clones.
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PMID:A single amino acid substitution in influenza hemagglutinin abrogates recognition by monoclonal antibody and a spectrum of subtype-specific L3T4+ T cell clones. 243 37

A previously identified Kd restricted epitope of influenza A virus nucleoprotein (147-161) was modified, resulting in recognition by Kd restricted cytotoxic T cells at significantly lower concentrations than the natural peptide sequence. This was achieved by first refining the epitope to the minimum determinant 147-158. Deletion of arginine 156 resulted in a peptide that was shown to be greatly superior in both dose response titrations and in its rate of association with cells to form targets. Analog peptides were tested to determine the important amino acid changes. These data suggest that T cell epitopes can be modified to result in improved immunological recognition.
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PMID:Enhanced recognition of a modified peptide antigen by cytotoxic T cells specific for influenza nucleoprotein. 244 84

Previous studies have demonstrated that certain amino acid substitutions in the alpha two domain at positions 152 and 156 in the alpha two helix of the HLA-A2 molecule can affect presentation of the influenza virus matrix peptide M1 55-73 without abolishing binding of the M1 peptide. HLA-A2.1-restricted M1 55-73 peptide-specific CTL lines obtained from almost all HLA-A2.1+ individuals fail to recognize the M1 peptide presented by site-directed mutants of HLA-A2 that have either a Val----Ala or Val----Gln substitution at position 152 or a Leu----Trp substitution at position 156. Only one HLA-A2+ individual (donor Q66, HLA-A2,-B53,-B63) has been found who is able to generate a unique repertoire of HLA-A2-restricted M1 peptide-specific CTL that can recognize peptide presented by HLA-A2 mutants with either an Ala or Gln substitution at position 152 or a Trp substitution at position 156. These Q66 M1 peptide-specific CTL could be selected by stimulation with M1 peptide-pulsed transfectants that express the mutant HLA-A2 gene with the Trp substitution at 156. To determine if the presence of the unique CTL repertoire could be attributed to a variant HLA-A2 molecule in Q66, sequences were determined from polymerase chain reaction-amplified segments of the HLA-A2 RNA. Two different HLA-A2 genes were found expressed in Q66 cells: one is identical to HLA-A2.1 and the other is identical to HLA-A2.2F (Gln----Arg at position 43, Val----Leu at position 95, and Leu----Trp at position 156). These results demonstrate that a different CTL repertoire specific for HLA-A2 plus the M1 55-73 peptide is generated in an individual that expresses both HLA-A2.1 and HLA-A2.2F compared to individuals who express HLA-A2.1 alone, and that the unique repertoire can be selected by the presence of an HLA-A2 molecule with a single amino acid substitution at position 156.
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PMID:A single amino acid substitution in HLA-A2 can alter the selection of the cytotoxic T lymphocyte repertoire that responds to influenza virus matrix peptide 55-73. 247 44

Crystallographic studies of the HLA-A2 molecule have led to the assignment of a putative peptide binding site that consists of a groove with a beta-pleated sheet floor bordered by two alpha-helices. A CTL-defined variant of HLA-A2, termed HLA-A2.2F, differs from the common A2.1 molecule by three amino acids: a Leu to Trp substitution at position 156 in the alpha-2 helix, a Val to Leu substitution at position 95 in the beta-sheet floor of the groove, and a Gln to Arg substitution at position 43 in a loop outside of the groove. Another HLA-A2 variant, termed CLA, has a single Phe to Tyr substitution at position 9 that is sterically located adjacent to position 95 in the beta-sheet floor of the groove. We have determined which of the amino acid substitutions at positions 9, 43, 95, or 156 could individually affect recognition by panels of A2.1 allospecific and A2.1-restricted influenza viral matrix peptide-specific CTL lines, using a panel of site-directed mutants and CLA. Recognition by allospecific CTL lines was generally unaffected by any one of the amino acid substitutions, but was eliminated by the double substitution at positions 95 and 156. Allorecognition by some CTL lines was eliminated by a single substitution at position 9 or 95. In contrast, recognition by A2.1-restricted matrix peptide specific CTL was totally eliminated by a single substitution at position 9 or 156. The substitution at position 43 in a loop away from the peptide binding groove had no effect on allorecognition or matrix peptide recognition. These results indicate that amino acid residues in the floor or alpha-2 helical wall of the peptide binding groove of the HLA-A2 molecule can differentially affect allorecognition and viral peptide recognition.
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PMID:Differential effects of amino acid substitutions in the beta-sheet floor and alpha-2 helix of HLA-A2 on recognition by alloreactive viral peptide-specific cytotoxic T lymphocytes. 247 17

Recognition of the HLA DR-peptide complex by an influenza haemagglutinin-specific T-cell clone was examined by assaying a variety of peptide analogues for their ability to be recognized. Consistent with earlier experiments arguing that the peptide blinds the restriction element in a helical conformation, acetylation of the amino terminus and amidation of the carboxy terminus of the natural determinant (residues 307-319) resulted in a peptide that exhibited both greater propensity to form a helix, as judged by circular dichroism, and the ability to stimulate the clone at concentrations approximately two orders of magnitude lower than the native sequence. The peptide was modelled into the potential antigen-combining site of HLA class II based on the ability of analogues containing point mutations to stimulate the T-cell clone. The working model was initially tested by examining the ability of Epstein-Barr-transformed B-cell lines expressing in different DR4 subtypes to present the native haemagglutinin sequence and analogues to the clone. The different alleles could be categorized as high, intermediate, or low responders based on the resulting proliferation. DR4 dw15 was a high-responding allele, dw4, 13, and 14 were intermediate-responding alleles, whereas dw10 was a low responder. Mutation of Gln to Arg at 312 in the haemagglutinin sequence converted the high and intermediate responders to non-responders, while turning the low-responding allele into an intermediate responder. Potential explanations for these effects are discussed in the context of the model of the complex between peptide and the major histocompatibility complex.
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PMID:Recognition of the HLA class II-peptide complex by T-cell receptor: reversal of major histocompatibility complex restriction of a T-cell clone by a point mutation in the peptide determinant. 247 72

The HLA restriction of a human T cell clone specific for residues 307-319 of influenza haemagglutinin was changed by the introduction of a point substitution in the peptide. Cells expressing HLA Dw1, DR4 Dw4, Dw13, Dw14, or Dw15 could present the natural haemagglutinin peptide to varying extents to the clone, but DR4 Dw10 could not. Replacement of glutamine-312 of the peptide with arginine produced an analogue that was recognized by the T cell clone only in the context of DR4 Dw10; neither DR1 nor any of the other DR4 alleles could present this peptide to the clone. The inability to bind either the natural or modified peptide was shown not to be the cause of the non-responsiveness. Rather, the differential stimulation of the clone appeared to arise from sequence variations between the DR alleles in residues comprising the beta-chain helix, which either affected recognition by directly contacting the T cell receptor or modified the conformation of the bound peptide. The latter effects were sufficiently subtle to modulate recognition by changing the fine details of the bound peptide but not to eliminate the capacity of the restriction element to bind the peptide.
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PMID:Reversal of HLA restriction by a point mutation in an antigenic peptide. 248 39

This study reports the synthesis of l-desamino-7-lysine- (fluorescein)-8-arginine-vasotocin (7-lys(flu) dAVT), and describes its biological activity in the isolated urinary bladder of the toad Bufo marinus. 7-lys(flu)dAVT was fully active in increasing bladder permeability to water. A half-maximal hydroosmotic response was obtained at a concentration of 3 x 10(-8) M. A unique feature of this analog was that its response was not readily reversed after removal of the analog from the serosal bathing solution. The residual response to 7-lys(flu) dAVT was abolished (reversibly) by reducing serosal bath pH from 7.4 to 6.0, suggesting that acidification inhibits the response to analog at a step after the interaction of the ligand with its receptor. Although 8-arginine-vasopressin (AVP) was about 20 times more potent than 7-lys(flu)dAVT in increasing membrane permeability to water, the response to AVP was readily reversed. Preincubation of bladders with 7-lys(flu)dAVT in the presence of AVP blocked the residual response to 7-lys(flu) dAVT. These studies suggest that 7-lys(flu)dAVT forms a stable and physiologically active complex with hydrosmotic toad bladder receptors, and it may, therefore, serve as a useful fluorescent marker for receptors in tissues from this and other species that use vasotocin as an antidiuretic/pressor principle.
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PMID:Synthesis and characterization of a long-acting fluorescent analog of vasotocin. 250 70


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