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Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using mutants of fowl plague virus (FRV) which have single temperature-sensitive (ts) mutations in some genes, an analysis was carried out on reisolates from children of 3-6 years, vaccinated with a monovaccine from recombinant strains of influenza type A virus. The recombinants were obtained by crossing of current epidemic strains of subtypes A (HINI) and a (H3N2) with the cold-adapted (XA) ts-donor of attenuation A/Leningrad/134/47/57 (H2N2) from which they, as a rule, inherited 5 ts-mutations in genes 1 (PB2), 2 (PB1), 5 (NP), 7 (M), and 8 (NS). All the reisolates were shown to retain the ts-phenotype. However, in the recombination test some reisolates (most frequently those isolated at late periods of vaccination infection) no ts-mutations could be found in 1-3 genes coding for proteins of the polymerase complex, less frequently for NP and NS proteins but not for M proteins.
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PMID:[The ts phenotype of reisolates from children inoculated with live cold-adapted influenza vaccine type A]. 169 28

Nucleotide sequences were determined for the RNA segments coding for proteins other than the hemagglutinin and neuraminidase of the A/Leningrad/134/57 (H2N2) wild-type (A/Len/wt) virus and its two cold-adapted (ca) and attenuated variants, A/Leningrad/134/17/57 (A/Len/17/ca) and A/Leningrad/134/47/57 (A/Len/47/ca) that are used in the U.S.S.R. in the preparation of reassortant live attenuated vaccines. Ten nucleotide differences were detected between the sequences of the A/Len/wt and A/Len/17/ca viruses; of these, eight were deduced to encode amino acid (aa) substitutions. One aa substitution each was predicted for the PB2, M1, M2, and NS2 proteins, whereas two aa substitutions each were predicted for the PB1, and PA proteins of the A/Len/17/ca virus. Four additional nucleotide changes were found in the genome of the A/Len/47/ca virus; three of these were detected to code for one additional aa substitution each for the PB2, PB1, and NP proteins.
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PMID:Sequence changes in the live attenuated, cold-adapted variants of influenza A/Leningrad/134/57 (H2N2) virus. 173 14

An analysis of ts-mutations in the genomes of native and cold-adapted variants of influenza A/Leningrad/134/57 (H2N2) virus based on the use of fowl plague virus ts mutants was carried out. The recombination test was done by the conventional method in chick embryo fibroblast culture (genes PB2, PB1, PA, NP, NA, M and NS) or cell systems permissive for reproduction of human influenza virus (gene HA). The cold-adapted strain A/Len/17 used for preparation of live influenza vaccine (LIV) for adults was shown to have 4 ts mutations: three in "internal" genes (PB2, NP, and M) and one in gene 4 coding for hemagglutinin (HA). The more attenuated cold-adapted donor A/Len/47 for preparation of similar LIV for children acquired three additional ts mutations: two (PB1 and NS) in "internal" genes and one in gene 6 coding for neuraminidase (NA). The accumulation of ts mutations in the genome of cold-adapter strains was found to be accompanied by a decrease in their pneumotropicity for mice as well as their detectability in different organs of these animals.
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PMID:[Mutations in the genes coding for hemagglutinin and neuraminidase in cold-adapted variants of the influenza virus A/Leningrad/134/57 (H2N2)]. 188 32

Crossing the cold-adapted B/Leningrad/14/17/55 strain with the temperature-sensitive virulent B/Ann Arbor/2/86 strain yielded a recombinant B/14/5/1 which, by the antigenic specificity of hemagglutinin and neuraminidase, corresponded to the B/Ann Arbor/2/86 strain but, like the attenuated donor, had the cold-adapter characteristics. The B/14/5/1 recombinant inherited the genes coding for proteins PB2, PB1, PA, NP, and M from the attenuated master strain and the genes coding for hemagglutinin, neuraminidase, and proteins NS from the virulent master strain. This strain was nonreactive for adults and for children with the initial anti-hemagglutinin antibody titre less than or equal to 1:20 (the reactogenic index being 1 and 0.9% respectively) and was moderately antigenic inducing a 4-fold or more rise of anti-hemagglutinins in the blood of 48.8% of seronegative adults and in 46.6% of seronegative children of 3 to 15 years of age. The highest indices of seroconversions (60%) were recorded in a group of preschool children.
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PMID:[Attenuated recombinant influenza type B virus obtained during crossing of virus B/Ann Arbor/2/86 with the cold-adapted strain B/Leningrad/14/17/55]. 260 42

Reproduction of cold-adapted (ca) strains of influenza virus in the lungs of white mice after separate and combined inoculation and the properties of isolates derived from the infected animals were studied. It was shown that after combined inoculation with ca and ts strains A/Leningrad/134/17/57 (H2N2) and A/PR/8/59/1 (H1N1) ca recombinants could develop loosing some ts mutations and possessing (unlike the master strains) pneumo-virulence for mice. All the pneumo-virulent reassortants inherited hemagglutinin from the ca A/PR/8/59/1 strain and PB1 protein from the ca A/Leningrad/134/17/57 strain. The results indicate that it is unsafe to construct live recombinant divaccines by combining the recombinants produced from different donors of attenuation.
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PMID:[The effect of amplifying reproduction of influenza virus in mouse lungs during simultaneous infection with two cold-adapted strains]. 260 39

Nucleotide sequences have been obtained for RNA segments encoding the PB2, PB1, PA, NP, M1, M2, NS1, and NS2 proteins of the influenza A/Ann Arbor/6/60 (H2N2) wild-type (wt) virus and its cold-adapted (ca) derivative that has been used for preparing investigational live attenuated vaccines. Twenty-four nucleotide differences between the ca and wt viruses were detected, of which 11 were deduced to code for amino acid substitutions in the ca virus proteins. One amino acid substitution each was predicted for the PB2, M2, and NS1 proteins. Two amino acid substitutions were predicted for the NP and the PA proteins. Four substitutions were predicted for the PB1 protein. The biological significance of mutations in the PB2, PB1, PA, and M2 genes of the ca virus is suggested by currently available genetic data, a comparison with other available influenza gene sequences, and the nature of the predicted amino acid changes. In addition, the sequence data confirm the close evolutionary relationship between the genomes of influenza A (H2N2) and influenza A (H3N2) viruses.
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PMID:Identification of sequence changes in the cold-adapted, live attenuated influenza vaccine strain, A/Ann Arbor/6/60 (H2N2). 297 19

Clinical studies previously demonstrated that live influenza A virus vaccines derived by genetic reassortment from the mating of influenza A/Ann Arbor/6/60 (H2N2) cold-adapted (ca) donor virus with epidemic wild-type influenza A viruses are reproducibly safe, infectious, immunogenic, and efficacious in the prevention of illness caused by challenge with virulent wild-type virus. These influenza A reassortant virus vaccines also express the ca and temperature sensitivity (ts) phenotypes in vitro, but the genes of the ca virus parent which specify the ca, ts, and attenuation (att) phenotypes have not adequately been defined. To identify the genes associated with each of these phenotypes, we isolated six single-gene substitution reassortant viruses, each of which inherited only one RNA segment from the ca parent virus and the remaining seven RNA segments from the A/Korea/1/82 (H3N2) wild-type virus parent. These were evaluated in vitro for their ca and ts phenotypes and in ferrets, hamsters, and seronegative adult volunteers for the att phenotype. We found that the polymerase PA gene of the ca parent specifies the ca phenotype and that the PB2 and PB1 genes independently specify the ts phenotype. The PA, M, PB2, and PB1 genes of the ca donor virus each contribute to the att phenotype. The finding that four genes of the ca donor virus contribute to the att phenotype provides a partial explanation for the observed phenotypic stability of ca reassortant viruses following replication in humans.
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PMID:Four viral genes independently contribute to attenuation of live influenza A/Ann Arbor/6/60 (H2N2) cold-adapted reassortant virus vaccines. 333 68

Consensus sequences for both wt and ca B/Ann Arbor/1/66 viral PB2, PB1, PA, NP, M, and NS genes were directly determined from vRNA using a combination of chemical and chain-termination sequencing methods. There were 105 sites of difference between the wt and ca sets of these six RNA genes. The differences resulted in 26 amino acid substitutions distributed over the six proteins. The sequence changes were compared to the sequences of other known influenza type B wt viruses to pinpoint those changes that were unique to the ca B/ann Arbor/1/66 virus. Of the 26 amino acid differences, only 11 were unique to the cold-adapted virus. These unique sites were distributed among five of the six genes. The NS protein had no amino acid substitutions. The sequence changes are discussed in terms of their probable mode of origin and selection, and in terms of their importance to the cold-adapted, temperature-sensitive, and attenuation phenotypes of ca B/AA/1/66 virus. The sequence and organization of the PB2 gene and predicted protein are also given. The PB2 gene was 2396 nucleotides long, and it encoded a predicted protein of 770 amino acids with a molecular weight of 88,035 Da for the wt virus and 88,072 Da for the ca virus. Both proteins were predominantly hydrophilic, and each had an overall charge of +24.5 at pH 7.0.
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PMID:Sequence comparison of wild-type and cold-adapted B/Ann Arbor/1/66 influenza virus genes. 335 2

Direct biochemical evidence has been obtained for the existence of mutations in all eight RNA segments of the A/Ann Arbor/6/60 cold-adapted (ca) mutant influenza virus strain as compared with its wild-type (wt) progenitor. Polyacrylamide gel electrophoresis (PAGE) of viral RNA revealed a change in the electrophoretic migration of RNA 2 (PB1). T1 oligonucleotide mapping revealed changes in two polymerase genes (the PB2 and PA genes), the hemagglutinin (HA) gene and the nucleoprotein (NP) gene. Analysis of S1 nuclease-treated RNA hybrids on polyacrylamide gels detected changes in the HA and neuraminidase (NA) genes. Partial DNA sequence analysis demonstrated a base sequence change in the matrix (M) protein gene that predicts an amino acid change in the M2 protein and a silent mutation in the non-structural (NS) protein gene. In addition, analysis of viral polypeptides by PAGE has so far revealed changes in the viral protein, PA. These findings directly demonstrate the existence of multiple mutations in the ca vaccine strain, a property that may provide reliably and stably attenuated vaccines that derive their six internal genes from the ca A/Ann Arbor/6/60 donor strain.
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PMID:Comparative studies of wild-type and cold-mutant (temperature-sensitive) influenza virus: detection of mutations in all genes of the A/Ann Arbor/6/60 (H2N2) mutant vaccine donor strain. 350 94

The phenotype and localization of ts mutations in genomes of the influenza A/Victoria/30-ir (A/Vic/30-ir) and A/Hong Kong/17-ir (A/HK/17-ir) cold-adapted (ca) viruses were studied. Using the recombination analysis in chick embryo fibroblasts (CEF) we determined that influenza A/HK/17-ir ca virus carries ts mutations in three "internal" genes, i.e., PB1, NP and M, and influenza A/Vic/30-ir ca virus carries ones in four genes, i.e., PA, NP, M and NS. We have revealed ts mutations for NA gene in none of these viruses. Prior to the analysis of ts mutations in HA gene of influenza A/HK/17-ir and A/Vic/30-ir ca viruses, three cloning steps were performed in chick embryos (CE) by the method of limiting dilutions at 34 degrees C followed by selection of some strains with the most prominent ts phenotype. The cloned strains with such phenotypes were shown to repeat stable results within the recombination analysis in CE, i.e., none from the cloned strains of A/HK/17-ir ca virus recombined in CE at 40 degrees C with the 46 ts mutant, while recombination of this mutant with the cloned A/Vic/30-ir ca strains led to formation of the ts progeny. Thereafter our data result in conclusion that ts mutations in the PA gene must lead to some insignificant contribution for the expression of general ts phenotype among the ca strains as far as this sign is clearly displayed by both viruses, although only one of them, i.e., A/HK/17-ir carries ts mutation in the HA gene.
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PMID:[ts-Mutations in the genomes of cold-adapted variants of influenza A/Hong Kong/1/68(H3N2) and A/Victoria/35/72(H3N2) viruses]. 833 43


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