Biological characteristics of a cold-adapted influenza A virus mutation residing on a polymerase gene

Odagiri, Takato; Tosaka, Aki; Ishida, Nakao; Maassab, Hunein F.

doi:10.1007/bf01310893

Cited by 7 publications

(6 citation statements)

References 33 publications

(14 reference statements)

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“…The PA subunit was obviously involved in increased activities in WSN-VN hybrids (Figure 4A and 4B). PB2 did not appear to be involved contrasting with previous studies on cold-adaptation [24], [25], [26]. Perhaps there are differences in the factors influencing stress at low and high temperatures.…”

Section: Discussioncontrasting

confidence: 93%

“…PB2 is also associated with efficient replication of cold adapted influenza virus [24], [25], [26]. More recently, it was suggested that the steady-state level of polymerase - cRNA complex is important for the thermal stability of influenza virus [37].…”

Section: Resultsmentioning

confidence: 99%

“…In fact, the avian PB2 subunit is required for replication at high temperatures [23], presumably because of the high body temperature of birds. Moreover, the PB2 subunit is associated with the efficient replication of cold adapted influenza virus [24], [25], [26]. In influenza B virus, the PB2 gene was also involved in cold-adaptation [27].…”

Section: Introductionmentioning

confidence: 99%

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Artificial Hybrids of Influenza A Virus RNA Polymerase Reveal PA Subunit Modulates Its Thermal Sensitivity

et al. 2010

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BackgroundInfluenza A virus can infect a variety of different hosts and therefore has to adapt to different host temperatures for its efficient viral replication. Influenza virus codes for an RNA polymerase of 3 subunits: PB1, PB2 and PA. It is well known that the PB2 subunit is involved in temperature sensitivity, such as cold adaptation. On the other hand the role of the PA subunit in thermal sensitivity is still poorly understood.Methodology/Principal FindingsTo test which polymerase subunit(s) were involved in thermal stress we reconstituted artificial hybrids of influenza RNA polymerase in ribonucleoprotein (RNP) complexes and measured steady-state levels of mRNA, cRNA and vRNA at different temperatures. The PA subunit was involved in modulating RNP activity under thermal stress. Residue 114 of the PA subunit was an important determinant of this activity.Conclusions/SignificanceThese findings suggested that influenza A virus may acquire an RNA polymerase adapted to different body temperatures of the host by reassortment of the RNA polymerase genes.

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Section: Discussioncontrasting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Artificial Hybrids of Influenza A Virus RNA Polymerase Reveal PA Subunit Modulates Its Thermal Sensitivity

et al. 2010

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“…The other three influenza viruses sequenced to date have leucine at residue 715 of their PA proteins. The PA gene has been demonstrated to be involved in the cold-adaptation and attenuation properties of the mutant (Odagiri et al, 1986;SnyderetaL, 1985SnyderetaL, , 1987, so this leucine to proline change may be relevant to virus phenotype.…”

Section: W T E S M I E a E S S V K E K O M T K E F F K N K S E T N P mentioning

confidence: 99%

Identification of sequence changes in the cold-adapted, live attenuated influenzavaccine strain, A/Ann Arbor/6/60 (H2N2)

COX¹,

KITAME²,

KENDAL³

et al. 1988

Virology

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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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“…Gene segment and virus (sub)type specific primers were selected in such a way that PCR products of dif ferent sizes are obtained for wild type virus and MDV specific primers and that wild type virus specific prim ers do not amplify MDV gene segments and vice versa. Twelve PCR programs that were used for genotyping of reassortant viruses in order to select 6 : 2 vaccine viruses are presented in Table 1 RNA was a popular assay in the 1980s [10,11,13,15]. However, this technique is laborious and time consum ing.…”

Section: Methodsmentioning

confidence: 99%

Genome composition analysis of reassortant influenza viruses used in seasonal and pandemic live attenuated influenza vaccine

Kiseleva

Voeten²,

Teley³

et al. 2011

Mol. Genet. Microbiol. Virol.

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Abstract-The cold adapted, temperature sensitive and attenuated influenza master donor viruses A/Lenin grad/134/17/57 (H2N2) and B/USSR/60/69 were used to generate vaccine viruses to be included in live attenuated influenza vaccine. These vaccine viruses typically are 6 : 2 reassortant viruses containing the gene segments of the surface antigens haemagglutinin and neuraminidase of current wild type influenza A and influenza B viruses with the gene segments encoding the internal viral proteins, conferring the cold adapted, temperature sensitive and attenuated phenotype, being inherited from the master donor viruses. The 6 : 2 reassortant viruses are selected from co infections between master donor virus and wild type viruses that the oretically may yield as many as 256 combinations of gene segments and thus 256 genetically different viruses. As the time to generate and isolate vaccine viruses is limited and because only 6 : 2 reassortant viruses are allowed as vaccine viruses, sboth selection and creening needs to be both rapid and unambiguous. The screen ing of reassortant viruses by RT PCRs using master donor virus and wild type virus specific primer sets is described to select both influenza A and influenza B 6 : 2 reassortant viruses to be used in seasonal and pan demic live attenuated vaccine, unambigously.

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Biological characteristics of a cold-adapted influenza A virus mutation residing on a polymerase gene

Cited by 7 publications

References 33 publications

Artificial Hybrids of Influenza A Virus RNA Polymerase Reveal PA Subunit Modulates Its Thermal Sensitivity

Artificial Hybrids of Influenza A Virus RNA Polymerase Reveal PA Subunit Modulates Its Thermal Sensitivity

Identification of sequence changes in the cold-adapted, live attenuated influenzavaccine strain, A/Ann Arbor/6/60 (H2N2)

Genome composition analysis of reassortant influenza viruses used in seasonal and pandemic live attenuated influenza vaccine

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