scholarly journals Molecular mechanisms of reversion to the ts+ (non-temperature-sensitive) phenotype of influenza A cold-adapted (ca) virus strains

2007 ◽  
Vol 88 (10) ◽  
pp. 2724-2729 ◽  
Author(s):  
T. M. Tsfasman ◽  
S. G. Markushin ◽  
I. I. Akopova ◽  
Y. Z. Ghendon
Keyword(s):  
Influenza A ◽  
Molecular Mechanisms ◽  
Direct Sequencing ◽  
Temperature Sensitive ◽  
Sequencing Data ◽  
Cold Adapted ◽  
Phenotypic Manifestation ◽  
Genes Encoding ◽  
Virus Strains ◽  
Temperature Sensitive Phenotype

A ts+ ca− (non-temperature-sensitive, non-cold-adapted) revertant of the A/Leningrad/134/47/57 ca strain influenza virus [A/Leningrad/134/47/ts+18/1957(H2N2)], obtained in our previous study, lost phenotypic manifestation of ts mutations by the PB2, NP and NS genes, although, according to sequencing data, it acquired only two true reversions of a mutation in the PB2 and PB1 genes. Direct sequencing showed the appearance of 27 additional mutations (13 coding) in the genes encoding the PB2, PB1, PA, NP, M and NS proteins of the revertant, along with the above-mentioned two true reversions. We conjecture that some of these mutations suppressed phenotypic manifestation of ts mutations in the NS and NP genes.

scholarly journals Specific temperature-induced perturbations of secondary mRNA structures are associated with the cold-adapted temperature-sensitive phenotype of influenza A virus

RNA Biology ◽  
2012 ◽  
Vol 9 (10) ◽  
pp. 1266-1274 ◽  
Author(s):  
Andrey Chursov ◽  
Sebastian J. Kopetzky ◽  
Ignaty Leshchiner ◽  
Ivan Kondofersky ◽  
Fabian J. Theis ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Temperature Sensitive ◽  
Cold Adapted ◽  
Specific Temperature ◽  
Temperature Sensitive Phenotype

PB2 and PA genes control the expression of the temperature-sensitive phenotype of cold-adapted B/USSR/60/69 influenza master donor virus

2009 ◽  
Vol 91 (4) ◽  
pp. 931-937 ◽  
Author(s):  
I. V. Kiseleva ◽  
J. T. M. Voeten ◽  
L. C. P. Teley ◽  
N. V. Larionova ◽  
S. K. M. Drieszen-van der Cruijsen ◽  
...  
Keyword(s):  
Temperature Sensitive ◽  
Cold Adapted ◽  
Temperature Sensitive Phenotype

ESCAPE OF A HIGHLY DEFECTIVE INFLUENZA A VIRUS MUTANT FROM ITS TEMPERATURE SENSITIVE PHENOTYPE BY EXTRAGENIC SUPPRESSION AND OTHER TYPES OF MUTATION

1980 ◽  
Vol 354 (1 Genetic Varia) ◽  
pp. 172-182 ◽  
Author(s):  
Brian R. Murphy ◽  
Mark D. Tolpin ◽  
Judith G. Massicot ◽  
Hyun Y. Kim ◽  
Robert H. Parrott ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Temperature Sensitive ◽  
Virus Mutant ◽  
Extragenic Suppression ◽  
Temperature Sensitive Phenotype

scholarly journals SAFETY AND IMMUNOGENICITY OF COLD-ADAPTED RECOMBINANT INFLUENZA VECTOR EXPRESSING ESAT-6 AND AG85А ANTIGENS OF M. TUBERCULOSIS

2017 ◽  
Vol 62 (6) ◽  
pp. 266-272 ◽  
Author(s):  
M. V. Sergeeva ◽  
A. A. Pulkina ◽  
K. A. Vasiliev ◽  
E. A. Romanovskaya-Romanko ◽  
A. B. Komissarov ◽  
...  
Keyword(s):  
Recombinant Virus ◽  
Viral Vectors ◽  
Mdck Cells ◽  
Immunofluorescent Staining ◽  
Temperature Sensitive ◽  
Ns1 Protein ◽  
Cold Adapted ◽  
New Generation ◽  
Type Response ◽  
Temperature Sensitive Phenotype

Recombinant viral vectors represent one of the most promising platforms for creating a new generation of vaccines against tuberculosis. We constructed a vaccine candidate based on a cold-adapted influenza vector with a truncated NS1 protein containing an insert of tuberculosis ESAT-6 and Ag85A antigens. The recombinant virus possessed a cold-adapted and temperature-sensitive phenotype and was attenuated for mice when administered intranasally. Immunofluorescent staining and Western blot showed the expression of ESAT-6 protein in MDCK cells infected by recombinant virus. After intranasal administration to mice, the recombinant virus stimulated a specific anti-tuberculosis CD4 + Th1-type response with the formation of polyfunctional antigen-specific T cells.

scholarly journals Comparative Study of the Temperature Sensitive, Cold Adapted and Attenuated Mutations Present in the Master Donor Viruses of the Two Commercial Human Live Attenuated Influenza Vaccines

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 928 ◽  
Author(s):  
Laura Rodriguez ◽  
Pilar Blanco-Lobo ◽  
Emma C. Reilly ◽  
Tatsuya Maehigashi ◽  
Aitor Nogales ◽  
...  
Keyword(s):  
Influenza A ◽  
Viral Disease ◽  
The United States ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Temperature Sensitive ◽  
Cold Adapted ◽  
Ann Arbor

Influenza viruses cause annual, seasonal infection across the globe. Vaccination represents the most effective strategy to prevent such infections and/or to reduce viral disease. Two major types of influenza vaccines are approved for human use: inactivated influenza vaccines (IIVs) and live attenuated influenza vaccines (LAIVs). Two Master Donor Virus (MDV) backbones have been used to create LAIVs against influenza A virus (IAV): the United States (US) A/Ann Arbor/6/60 (AA) and the Russian A/Leningrad/134/17/57 (Len) H2N2 viruses. The mutations responsible for the temperature sensitive (ts), cold-adapted (ca) and attenuated (att) phenotypes of the two MDVs have been previously identified and genetically mapped. However, a direct comparison of the contribution of these residues to viral attenuation, immunogenicity and protection efficacy has not been conducted. Here, we compared the In vitro and in vivo phenotype of recombinant influenza A/Puerto Rico/8/34 H1N1 (PR8) viruses containing the ts, ca and att mutations of the US (PR8/AA) and the Russian (PR8/Len) MDVs. Our results show that PR8/Len is more attenuated in vivo than PR8/AA, although both viruses induced similar levels of humoral and cellular responses, and protection against homologous and heterologous viral challenges. Our findings support the feasibility of using a different virus backbone as MDV for the development of improved LAIVs for the prevention of IAV infections.

scholarly journals Introduction of a Temperature-Sensitive Phenotype into Influenza A/WSN/33 Virus by Altering the Basic Amino Acid Domain of Influenza Virus Matrix Protein

2004 ◽  
Vol 78 (18) ◽  
pp. 9585-9591 ◽  
Author(s):  
Teresa Liu ◽  
Zhiping Ye
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Viral Replication ◽  
Zinc Finger ◽  
Nuclear Export ◽  
Influenza A ◽  
Double Mutant ◽  
Temperature Sensitive ◽  
Zinc Finger Motif ◽  
Temperature Sensitive Phenotype

ABSTRACT Our previous studies with influenza A viruses indicated that the association of M1 with viral RNA and nucleoprotein (NP) is required for the efficient formation of helical ribonucleoprotein (RNP) and for the nuclear export of RNPs. RNA-binding domains of M1 map to the following two independent regions: a zinc finger motif at amino acid positions 148 to 162 and a series of basic amino acids (RKLKR) at amino acid positions 101 to 105. Altering the zinc finger motif of M1 reduces viral growth slightly. A substitution of Ser for Arg at either position 101 or position 105 of the RKLKR domain partially reduces the nuclear export of RNP and viral replication. To further understand the role of the zinc finger motif and the RKLKR domain in viral assembly and replication, we introduced multiple mutations by using reverse genetics to modify these regions of the M gene of influenza virus A/WSN/33. Of multiple mutants analyzed, a double mutant, R101S-R105S, of RKLKR resulted in a temperature-sensitive phenotype. The R101S-R105S double mutant had a greatly reduced ratio of M1 to NP in viral particles and a weaker binding of M1 to RNPs. These results suggest that mutations can be introduced into the RKLKR domain to control viral replication.

Genetic factors associated with loss of the temperature-sensitive phenotype of the influenza A/Alaska/77-ts-1A2 recombinant during growth in vivo

Virology ◽  
1981 ◽  
Vol 112 (2) ◽  
pp. 505-517 ◽  
Author(s):  
Mark D. Tolpin ◽  
Judith G. Massicot ◽  
Mary G. Mullinix ◽  
Hyun Wha Kim ◽  
Robert H. Parrott ◽  
...  
Keyword(s):  
Influenza A ◽  
Genetic Factors ◽  
Temperature Sensitive ◽  
Factors Associated ◽  
Temperature Sensitive Phenotype
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