Трудности диагностики детского мультисистемного воспалительного синдрома, ассоциированного с COVID-19, в сочетании с ранней стадией первичной инфекции, вызванной вирусом Эпштейна-Барр

Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 is a rare life-threatening immunopathological complication of COVID-19 that develops 1-6 weeks after the acute coronavirus infection. MIS-C is characterized by fever and multiorgan inflammation.We present a clinical case of a 10-year-old boy with skin lesions at the onset of MIS-C (erythematous malar rash, lacelike rash on the trunk and extremities and petechiae) with macrophage activation syndrome development and the early stage of primary Epstein-Barr virus infection (EBV infection) which required the exclusion of X-linked lymphoproliferative disease.This clinical case demonstrates the complexity of diagnosis in MIS-C with skin manifestations at the onset of the disease, especially with concurrent activation of other infections, particularly EBV infection.Детский мультисистемный воспалительный синдром (ДМВС), ассоциированный с COVID-19 — это редкое жизнеугрожающее иммунопатологическое осложнение, развивающееся через 1-6 недель после перенесенной новой коронавирусной инфекции, протекающее с лихорадкой и мультиорганным воспалением.В статье представлено клиническое наблюдение мальчика в возрасте 10 лет с поражением кожи в дебюте ДМВС в виде полиморфной сыпи (эритема на щеках, сыпь в виде кружевного рисунка на туловище и конечностях, петехии), с одновременным обнаружением маркеров ранней стадии первичной инфекции, вызванной вирусом Эпштейна-Барр (ЭБВ), а также развитием гемофагоцитарного синдрома, что потребовало исключения Х-сцепленного лимфопролиферативного синдрома.Данное клиническое наблюдение демонстрирует сложность диагностического поиска при кожных проявлениях в дебюте ДМВС, а также возможность сочетания ДМВС с другими инфекциями, в частности с ЭБВ-инфекцией

Study of the biological properties of attenuated variants of the virulent A/WSN/33 strain of influenza virus, obtained by the site-specific mutagenesis of PB2-gene

Aim. Study of biological properties of attenuated  variants of the virulent A/WSN/33 strain of influenza virus, obtained by the site-specific mutagenesis of PB2-gene. Materials and methods. Site-specific mutants of A/WSN/33 of influenza virus, having in PB2-gene ts-mutations from genome of cold-adapted (CA) master-strains: A/Ann  Arbor/6/60 (H2N2); A/Leningrad/134/17/57 (H2N2); A/Krasnodar/101/35/59 (H2N2) were obtained  with help of reverse genetics methods.  The ts-phenotype, att-phenotype, immunogenicity and protective efficacy in homologous and heterologous control infections were studied in the obtained site-specific mutants. Results. It was shown that the inclusion in the PB2-gene of the virulent A/WSN/33 strain as single mutations and a combination of mutations from the genomes of CA donor-strains leads to a change in the ts-phenotype and att-phenotype of the mutants obtained. These mutants had high protective efficacy in homologous and heterologous control infection. Conclusion. The results obtained allow us to consider the site-specific mutants of influenza virus as possible candidates for live influenza vaccines

INCLUSION OF SITE-SPECIFIC MUTATIONS INTO CONSERVATIVE SEGMENTS OF РА-GENE RESULTS IN ATTENUATION OF VIRULENT INFLUENZA VIRUS STRAIN A/WSN/33

Aim. Study the possibility of obtaining attenuated variants of influenza virus by including specially selected site-specific mutations into a conservative sequence of PA-gene (terminal segment of COOH-domain of the PA-gene) of a virulent strain. Materials and methods. А/ WSN/33 - a virulent strain of influenza virus was used in the study. I nclusion of site-specific mutations into PA-gene of the A/WSN/33 virulent strain was carried out using a two-step mutation PCR. Cloning was carried out using GoldenGate reaction. 8-plasmid transfection system based on pHW2000 vector was used. Transformation was carried out in rubidium competent bacterial cells of DH5a strain. Transfection was done using Lipofectamine LTX (Invitrogen) reagent in a 293T and MDCK cells’ co-culture. Results. Transfectants with F658A substitution in the COOH-domain of the PA-gene were shown to acquire ts-phenotype and sharply reduce the ability to reproduce in mice lungs. Introduction of F658A substitution into COOH-domain of the PA-gene in combination with introduction of ts-mutations from ca influenza virus strains into the genome of the virulent strain resulted in obtaining transfectants that have phenotypic characteristics typical for live influenza vaccine candidates. Conclusion. The ability to obtain attenuated variants of influenza viruses by introducing specially selected site-specific mutations into conservative sequence of the PA-gene is shown