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Probable Mechanisms of COVID-19 Pathogenesis ; Вероятные механизмы патогенеза COVID-19

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  • Additional Information
    • Publication Information:
      Bashkir State Medical University
    • Publication Date:
      2020
    • Collection:
      Creative surgery and oncology (E-Journal) / Креативная хирургия и онкология
    • Abstract:
      This review paper focuses on the search for innovative directions in the study of COVID­19 viral infection with the purpose of improving the methods of its treatment and vaccination. Thus far, comprehensive data have been obtained on the ability of nonretroviral RNA viruses, including those replicated in the cytoplasm, to integrate fragments of their genomes into the host DNA. This mechanism provided by the reverse transcriptase and integrase of endogenous retroelements leads to the persistence of nonretroviral RNA viruses through the expression of viral proteins by the host genome, which may serve as a prerequisite for the survival of such viruses. DNA integration events play a role in the development of both the immunological response and protective antiviral responses through the RNA interference system. These mechanisms may depend on the phylogenetically ancient fossils of nonretroviral RNA sequences in animal genomes. The discovery of SARS-CoV-2 fragments in COVID­19 recovered patients suggests that the pathogenesis of this disease may be associated with the integration of SARS-CoV-2 genome fragments in the human genome by means of proteins of endogenous retroviral elements. This assumption can be confirmed by the data about the development in older patients of predominantly severe forms of COVID­19 with “hyperactive” immune reactions, which normally weaken with ageing. This may be attributed to age­related abnormal activation of retrocells, which contribute to reverse transcription and integration of exogenous viruses. This assumption is supported by the presence of coronavirus components in the nuclei of infected cells and the change in the expression of LINE­1 in the lung tissue cells of SARS patients. Due to the probable role of retrocells in the COVID­19 pathogenesis, LINE­1 reverse transcriptase inhibitors and targeted therapy using microRNAs may be offered as promising treatments for COVID­19. ; Обзорная статья посвящена поиску инновационных направлений в исследовании вирусной инфекции COVID­19 для улучшения методов вакцинопрофилактики и лечения болезни. В настоящее время получены убедительные данные о способности неретровирусных РНК­вирусов, в том числе реплицирующихся в цитоплазме, интегрировать фрагменты своих геномов в ДНК хозяев. Это обеспечивается благодаря обратной транскриптазе и интегразе эндогенных ретроэлементов и приводит к персистенции неретровирусных РНК­вирусов за счет экспрессии вирусных белков геномом хозяина, что может служить необходимым условием для поддержания жизнедеятельности вирусов. Интеграционные события играют роль в развитии иммунологического ответа организма и в защитных противовирусных реакциях с помощью системы РНК­интерференции. Данные механизмы могут зависеть от филогенетически древних остатков последовательностей неретровирусных РНК­вирусов в геномах животных. Обнаружение фрагментов SARS-CoV-2 у выздоровевших от COVID­ 19 позволяет сделать предположение о том, что в патогенезе болезни могли бы играть роль события встройки кДНК фрагментов генома вируса SARS-CoV-2 в геном человека с использованием белков эндогенных ретроэлементов. Подтверждением могут служить данные о развитии у пожилых пациентов преимущественно тяжелых форм COVID­19 с гиперактивностью иммунных реакций, несмотря на их снижение при старении, что может быть обусловлено возрастной аномальной активацией ретроэлементов, которые способствуют обратной транскрипции и встройке экзогенных вирусов. В пользу данного предположения говорят данные о наличии компонентов коронавирусов в ядрах инфицированных клеток и об изменении экспрессии LINE­1 в клетках легочной ткани больных SARS. В связи с вероятной ролью ретроэлементов в патогенезе COVID­19 в качестве перспективных направлений лечения COVID­19 могут быть предложены ингибиторы обратной транскриптазы LINE­1 и таргетная терапия с использованием микро­РНК.
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    • Accession Number:
      10.24060/2076-3093-2020-10-4-302-310
    • Online Access:
      https://doi.org/10.24060/2076-3093-2020-10-4-302-310
      https://doi.org/10.1016/s0140-6736(66)92364-6
      https://doi.org/10.1159/000149883
      https://doi.org/10.1093/oxfordjournals.aje.a121171
      https://doi.org/10.1016/s0140-6736(03)13077-2
      https://doi.org/10.1016/j.idc.2019.08.001
      https://doi.org/10.1016/j.ijid.2020.01.009
      https://doi.org/10.1021/acs.jproteome.0c00129
      https://doi.org/10.7150/ijbs.45134
      https://doi.org/10.1038/s41579-018-0118-9
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    • Accession Number:
      edsbas.6305B76