chuka_lis (chuka_lis) wrote,

Клеточный генный ответ на коронавирус

Не является сбаллансированным, и является уникальным в скоем роде, как показывает работа ученых в журнале Сell.
САРС 2 подавляет сигналы от пораженных клеток, способные стимулировать выработку интерферонов (врожденный иммунитет) иммунными клетками (и получить быстрый и адекватный имумнный ответ на вирус). При этом вирус активно реплицируется в зараженных клетках и разрушает их, в процессе чего те посылают сигналы - хемокины, активирующие и привлекающие лейкоциты, которые вырабатывают много интерлейкинов, усиливающих воспалительную реакцию.

SARS-CoV-2 infection induces low IFN-I and -III levels with a moderate ISG response

Strong chemokine expression is consistent across in vitro, ex vivo, and in vivo models

Low innate antiviral defenses and high pro-inflammatory cues contribute to COVID-19

Из этой статьи кстати следует, что  лечение интерферонами, начатое на ранеей стадии болезни, может и помочь избавиться от вируса (тк добавка интерферонов очень быстро снижает репликацию вируа в культуре), и снизить сильный воспалительный ответ (который, считают, ответственнен за отеки и эффекты коагуляцииу больных)
"...analyses indicate that the transcriptional response in cells that allows high replication of SARS-CoV-2 is significantly different from the host response of all other viruses tested demonstrate that addition of IFN-I resulted in a dramatic reduction in virus replication,
,,,high induction of these (хемокинов) genes in SARS-CoV-2 infection is independent of IFN-I and -III signaling
..Gene enrichment analyses of differentially expressed transcripts illustrate a diminished IFN-I signaling biology for SARS-CoV-2..
IFN-I and IFN-III are undetectable, but a very small subset of ISGs is induced ...
Despite a complete lack of IFN expression, the response to SARS-CoV-2 in NHBE cells still elicited a strong chemotactic and inflammatory response, indicated by expression of CCL20, CXCL1, IL-1B, IL-6, CXCL3, CXCL5, CXCL6, CXCL2, CXCL16, and TNF...
SARS-CoV-2 in NHBE cells also triggers some unique pathways, including a response to IFN-II, and significant enrichment in chemokine signaling..
В модели на животных генная активация шла по аналогичному типу, как и в клеточных линиях:
SARS-CoV-2 generates a unique gene signature enriched for cell death and leukocyte activation, including transcripts such as IL1A and CXCL8... By day 14, we detected no viral reads for SARS-CoV-2, and the observed cytokines returned to baseline, with the exception of IL-6 and IL1RN or IL1RA, which remained elevated.
Gene enrichment analysis of differentially expressed transcripts implicated two populations of immune cell signatures. The first population included common markers for monocytes and lymphocytes,.. Intriguingly, unique gene signatures from SARS-CoV-2-infected trachea align with those of progenitor cells from the hematopoietic lineage, suggesting that infection may be inducing hematopoiesis..
Образцы тканей легких показали похожую картину у людей
To this end, we first compared post-mortem lung samples from COVID-19-positive patients with biopsied healthy lung tissue from uninfected individuals. Transcriptional profiling of these samples,.. demonstrated ∼2,000 differentially expressed genes with enrichment for the innate and humoral responses ..
Genes significantly induced in response to SARS-CoV-2 included a subset of ISGs with no IFN-I or IFN-III detected by RNA-seq or semiquantitative PCR ... In addition to genes implicated in innate antiviral immunity, SARS-CoV-2 also induced robust levels of chemokines, including CCL2, CCL8, and CCL11..
..we obtained serum from two cohorts of individuals from the Kaiser Santa Clara testing facility (Santa Clara, CA). These two cohorts tested positive for SARS-CoV-2 by nasopharyngeal swabs or were admitted to the hospital for non-COVID-19-related respiratory issues (n = 24 for each group). During initial analyses, these serum samples consistently tested negative for IFNβ and the IFNλ family of IFNs . Moreover, analyses of cytokines and chemokines quantified in individual serum samples revealed enhancement of generalized inflammation among COVID-19 patients, marked by a significant increase in circulating IL-6, IL1RA, CCL2, CCL8 CXCL2, CXCL8, CXCL9, and CXCL16 levels ). Significant elevation of CXCL9 and CXCL16 (chemoattractants of T or natural killer (NK) cells, respectively), CCL8 and CCL2 (which recruit monocytes and/or macrophages), and CXCL8 (a classic neutrophil chemoattractant) suggest that the presence of these cells may be a primary driver of the signature pathology observed in COVID-19 patients.
Tags: иммунитет, коронавирус, статьи, эпидемия
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