Microbiology Independent Research Journal (MIR Journal)

Расширенный поиск
Том 8, № 1 (2021)
1-9 584

The influenza A virus genome consists of eight segments of negative-sense RNA that encode up to 18 proteins. During the process of viral replication, positive-sense (+)RNA (cRNA) or messenger RNA (mRNA) is synthesized. Today, there is only a partial understanding of the function of several secondary structures within vRNA and cRNA promoters, and splice sites in the M and NS genes. The most precise secondary structure of (+)RNA has been determined for the NS segment of influenza A virus.  
The influenza A virus NS gene features two regions with a conserved mRNA secondary structure located near splice sites. Here, we compared 4 variants of the A/Puerto Rico/8/1934 strain featuring different combinations of secondary structures at the NS segment (+)RNA regions 82-148 and 497-564. We found that RNA structures did not affect viral replication in cell culture. However, one of the viruses demonstrated lower NS1 and NEP expression levels during early stage cell infection as well as reduced pathogenicity in mice compared to other variants. In particular, this virus is characterized by an RNA hairpin in the 82-148 region and a stable hairpin in the 497-564 region.

10-17 503

В последние годы в мире наблюдается рост числа инфекционных заболеваний, вызванных Clostridium difficile со значительным увеличением рецидивов и смертности, в том числе среди онкологических больных – пациентов стационаров. Отмечается также рост резистентности Clostridium difficile к препаратам первой линии терапии, а именно к метронидазолу и ванкомицину, что делает актуальным поиск новых методов лечения и профилактики данной инфекции. Мы проанализировали данные последних лет по методам культивирования Clostridium difficile, связанные с получением чистой культуры Clostridium difficile и других анаэробных энтеропатогенов при энтероколитах у детей с онкопатологией на фоне приема антимикробных препаратов, а также современные подходы к терапии данной инфекции. 

18-26 482

Окружающая среда при производстве лекарственных средств должна обеспечивать минимальный риск микробного загрязнения продукта. Нами были изучены закономерности изменения уровня микробного загрязнения в чистых помещениях на примере учебно-научного Модуля чистых помещений Отделения биотехнологий ИАТЭ НИЯУ «МИФИ» (Обнинск). Показано, что уровень загрязнения рабочих поверхностей увеличивается при наличии в помещениях работающего персонала. Степень микробного загрязнения воздушной среды в зависимости от вида выполняемых работ и количества персонала изменяется незначительно. Подтверждено соответствие исследуемых чистых помещений классу чистоты D по микробиологической чистоте. Сделан вывод о необходимости чаще осуществлять контроль микробного загрязнения помещений, а также усилить санитарно-гигиенические мероприятия для устранения источников спорообразующей микрофлоры.

27-37 201

We constructed a reporter influenza A/Puerto Rico/8/1934 virus expressing truncated 124aa N-terminal NS1 protein fused to a luciferase reporter sequence (NanoLuc) without signal peptide. The reproduction activity of the vector correlated well with the luminescent activity in the lysates of infected cell cultures or mouse respiratory organ suspensions. Surprisingly, we found that luciferase enzymatic activity was present not only in the intracellular compartments but also in cell culture supernatants as well as in the sera or bronchiolar lavages of infected mice. This fact allowed us to formulate a working hypothesis about the extracellular delivery mechanism of the NS1 protein. To test this idea, we conducted co-transfection experiments in Vero cells with different combinations of plasmids encoding influenza genomic segments and chimeric NS1-NanoLuc encoding plasmid. We found that the emergence of the luciferase reporter in the extracellular compartment was promoted by the formation of the ribonucleoprotein complex (RNP) from the co-transfection of plasmids expressing PB1, PB2, PA, and NP proteins. Therefore, influenza NS1 protein may be delivered to the extracellular compartment together with the nascent RNP complexes during the maturation of virus particles.

38-40 106

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease (COVID-19) and ongoing pandemic that has devastated humankind. During the COVID-19 pandemic, it was noticed that the mortality rate in men is higher than that in women. The membrane (M) protein of SARS-CoV-2 plays a pivotal role in the viral life cycle regulating intracellular trafficking and processing of spike (S) protein. In infected individuals, M protein inhibits the conversion of active testosterone to its inactive form through its interaction with Aldo-keto reductase family 1 member C2 (AKR1C2) protein. This leads to the high availability of active testosterone and boosts the formation of its complex with an androgen receptor that in turn promotes the transcription of the transmembrane protease serine 2 (TMPRSS2) gene. TMPRSS2 is known to play a pivotal role in the priming of S protein that is necessary for the SARS-CoV-2 entry into the host cell. Therefore, the interaction of the M protein of SARSCoV-2 with AKR1C2 eventually leads to the upregulation of the transcription of the TMPRSS2 gene that results in an enhanced viral infection and in turn higher mortality in men. The interaction of M protein with AKR1C2 could be a possible target for SARSCoV-2 antiviral drug design.

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ISSN 2500-2236 (Online)