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1.
Leukemia ; 31(11): 2515-2522, 2017 11.
Article in English | MEDLINE | ID: mdl-28360415

ABSTRACT

With combined antiretroviral therapy (cART), the risk for HIV-infected individuals to develop a non-Hodgkin lymphoma is diminished. However, the incidence of Burkitt lymphoma (BL) remains strikingly elevated. Most BL present a t(8;14) chromosomal translocation which must take place at a time of spatial proximity between the translocation partners. The two partner genes, MYC and IGH, were found colocalized only very rarely in the nuclei of normal peripheral blood B-cells examined using 3D-FISH while circulating B-cells from HIV-infected individuals whose exhibited consistently elevated levels of MYC-IGH colocalization. In vitro, incubating normal B-cells from healthy donors with a transcriptionally active form of the HIV-encoded Tat protein rapidly activated transcription of the nuclease-encoding RAG1 gene. This created DNA damage, including in the MYC gene locus which then moved towards the center of the nucleus where it sustainably colocalized with IGH up to 10-fold more frequently than in controls. In vivo, this could be sufficient to account for the elevated risk of BL-specific chromosomal translocations which would occur following DNA double strand breaks triggered by AID in secondary lymph nodes at the final stage of immunoglobulin gene maturation. New therapeutic attitudes can be envisioned to prevent BL in this high risk group.


Subject(s)
B-Lymphocytes/metabolism , Burkitt Lymphoma/genetics , Gene Products, tat/physiology , Genes, myc , Immunoglobulin Heavy Chains/genetics , Aged , Female , Humans , Male , Middle Aged
2.
Article in Russian | MEDLINE | ID: mdl-26829850

ABSTRACT

AIM: Study of ts, ca, att phenotype, immunogenicity and protective effectiveness of reassortants obtained by a way of recombination of a new influenza cold-adapted (ca) strain donor of attenuation A/Krasnodar/101/35/59 (H2N2) and virulent strain of influenza virus. MATERIALS AND METHODS: Viruses were used: ca strain A/Krasnodar/101/35.59 (H2N2), virulent strains: A/Kumamoto/102/02 (H3N2) and A/Bern/07/95. For determination of ts and ca phenotype, titration of viruses in chicken embryos was carried out simultaneously at optimal, decreased and increased temperature. Protective effect of immunization was evaluated during intranasal infection of mice with a virulent strain of influenza virus. RESULTS: All the obtained reassortants possessed 6 internal genes from strain-donor of attenuation and 2 genes, coding HA and NA-proteins from virulent strains. Ca reassortants were characterized by ts and ca phenotype, had antigenic specificity and good immunogenicity, had high protective effectiveness. CONCLUSION: The data obtained indicate on the perspectiveness of ca strain A/Krasnodar/101/35/59 (H2N2)as a donor of attenuation for live influenza vaccines.


Subject(s)
Immunization , Influenza Vaccines/immunology , Influenza, Human/immunology , Vaccines, Attenuated/immunology , Animals , Chick Embryo , Cold Temperature , Humans , Influenza A Virus, H2N2 Subtype/immunology , Influenza A Virus, H2N2 Subtype/pathogenicity , Influenza A Virus, H3N2 Subtype/immunology , Influenza A Virus, H3N2 Subtype/pathogenicity , Influenza Vaccines/therapeutic use , Influenza, Human/prevention & control , Influenza, Human/virology , Mice , Vaccines, Attenuated/therapeutic use
3.
Vopr Virusol ; 58(1): 11-7, 2013.
Article in Russian | MEDLINE | ID: mdl-23785755

ABSTRACT

Cold-adapted (CA) strains A/Krasnodar/35 and B/Victoria/63 were isolated using passages of A/Krasnodar/101/59 and B/Victoria/2/87 wild type strains at low temperatures. The resulting CA strains possessed TS and CA phenotypes and had a reduced ability to reproduce in mouse lungs and nasal turbinates. They displayed a high protective efficacy in experiments on mice. The two CA strains reproduced well in chick embryos and MDCK cell line without change of TS and CA markers. The CA A/Krasnodar/35 strain during passages at low temperature acquired 13 mutations in the 6 internal genes, 8 of those mutations led to amino acid changes. The CA B/Victoria/63 strain acquired 8 mutations in the internal genes, 6 of which led to amino acid changes. The intranasal vaccination of mice with the CA A/Krasnodar/35 strain led to a transitory suppression of various lymphocyte subpopulations, as well as to an increase in the number of some other cell types. The CA strains in question may be used in the future as attenuation donors for live influenza vaccines.


Subject(s)
Adaptation, Physiological/genetics , Cold Temperature , Influenza A Virus, H2N2 Subtype , Influenza Vaccines , Mutation , Amino Acid Substitution , Animals , Cell Line , Chick Embryo , Dogs , Humans , Influenza A Virus, H2N2 Subtype/genetics , Influenza A Virus, H2N2 Subtype/immunology , Influenza A Virus, H2N2 Subtype/metabolism , Influenza Vaccines/biosynthesis , Influenza Vaccines/genetics , Influenza Vaccines/immunology , Mice , Vaccines, Attenuated/biosynthesis , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology
4.
J Gen Virol ; 88(Pt 10): 2724-2729, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17872525

ABSTRACT

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.


Subject(s)
Influenza A Virus, H2N2 Subtype/physiology , Acclimatization , Cold Temperature , Genetic Complementation Test , Genotype , Humans , Influenza A Virus, H2N2 Subtype/genetics , Influenza, Human/immunology , Influenza, Human/prevention & control , Mutation , Phenotype , Polymorphism, Single-Stranded Conformational , Recombination, Genetic , Viral Nonstructural Proteins/genetics
5.
Vopr Virusol ; 51(5): 17-22, 2006.
Article in Russian | MEDLINE | ID: mdl-17087060

ABSTRACT

A ts+ revertant of cold-adapted (ca) strain A/Leningrad/134/47/57--the attenuation donor for live influenza reassortant vaccines--was obtained by passages of the ca strain in chick embryos at nonpermissive temperatures. The ts+ revertant acquired the ability to grow in chick embryos at 40 degrees C and lost the capacity to reproduce there at 25 degrees C. A complementation-recombination test using the fowl plague virus (FPV0 ts-mutants showed the loss of the ts-phenotype in the RNA-segments of ts+ revertants' genome coding for PB2, NP, and NS (NS2) proteins. However, PCR-restriction analysis revealed a true reversion in RNA-segment coding for PB2 protein only. All the investigated mutations in the ts+ revertant genome were preserved. This phenomenon could be explained by the appearance of intragenic and extragenic suppression mutations in the ts+ revertant genome. The data of the complementation-recombination test suggest that reversion of ts-phenotype occurs more frequently due to extra- or intragenic suppression rather than as a result of a true mutation loss. Estimation of the genetic stability of vaccine ca strains of influenza virus should be based on the combined use of PCR-restriction and complementation tests.


Subject(s)
Influenza A Virus, H2N2 Subtype/genetics , Reassortant Viruses/genetics , Recombination, Genetic , Suppression, Genetic , Adaptation, Physiological , Animals , Chick Embryo , Genetic Complementation Test , Hot Temperature , Influenza A Virus, H2N2 Subtype/physiology , Polymerase Chain Reaction , Reassortant Viruses/physiology , Serial Passage , Viral Proteins/genetics , Virus Replication
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