Epigenetic Lens to Visualize the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection in COVID-19 Pandemic

In <20 years, we have witnessed three different epidemics with coronaviruses, SARS-CoV, MERS-CoV, and SARS-CoV-2 in human populations, causing widespread mortality. SARS-CoV-2, through its rapid global spread, has led to the pandemic that we call COVID-19. As of February 1, 2021, the global infections linked to SARS-CoV-2 stand at 103,503,340, with 2,236,960 deaths, and 75,108,099 recoveries. This review attempts to highlight host-pathogen interaction with particular emphasis on the role of epigenetic machinery in regulating the disease. Although researchers, since the start of the pandemic, have been intensely engaged in diverse areas to understand the mechanisms involved in SARS-CoV-2 infection to find answers that can bring about innovative ways to swiftly treat and prevent disease progression, this review provides an overview on how the host epigenetics is modulated and subverted by SARS-CoV-2 to enter the host cells and drive immunopathogenesis. Epigenetics is the study that combines genetic and non-genetic factors controlling phenotypic variation, which are primarily a consequence of external and environmental stimuli. These stimuli alter the activity of a gene without impinging on the DNA code. In viral-host interactions, DNA/RNA methylation, non-coding RNAs, chromatin remodeling, and histone modifications are known to regulate and modulate host gene expression patterns. Viruses such as Coronaviruses (an RNA virus) show intrinsic association with these processes. They have evolved the ability to tamper with host epigenetic machinery to interfere with immune sensing pathways to evade host immune response, thereby enhancing its replication and pathogenesis post-entry. These epigenetic alterations allow the virus to weaken the host's immune response to successfully spread infection. How this occurs, and what epigenetic mechanisms are altered is poorly understood both for coronaviruses and other respiratory RNA viruses. The review highlights several cutting-edge aspects of epigenetic work primarily pertinent to SARS-CoV-2, which has been published between 2019 and 2020 to showcase the current knowledge both in terms of success and failures and take lessons that will assist us in understanding the disease to develop better treatments suited to kill SARS-CoV-2.

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COVID-19 : histoire, pathogenèse et réponse immunitaire de l'hôte

Batna Journal of Medical Sciences (BJMS) ◽

10.48087/bjmsra.2021.8110 ◽

2021 ◽

Vol 8 (1) ◽

pp. 52-58

Author(s):

Takieddine Hamadou ◽

◽

Imene Hamadou ◽

Ahmed Menad ◽

Somia Bouameur ◽

...

Keyword(s):

Immune Response ◽

Current Knowledge ◽

Rna Virus ◽

Multiorgan Failure ◽

Alveolar Epithelial Cells ◽

Host Cells ◽

Disease Spread ◽

Structural Proteins ◽

Unknown Etiology ◽

Presenting Symptoms

By the end of 2019, pneumonia of unknown etiology occurred in Wuhan, China. Local hospitals started receiving patients presenting symptoms like dry cough, fatigue, and breathing difficulties, most of these patients were linked to the Huanan seafood market, Wuhan, China. The pandemic was afterward confirmed to be associated with a novel coronavirus. The virus spread quickly from Wuhan to other provinces of China, then from china to the rest of the world causing thereby one of the most brutal pandemics in the world’s history. SARS-CoV2 has a long incubation period ranging from 3 to 7 days and can go up to 14 days in some cases which makes the infection difficult to be detected early and subsequently the disease spread harder to be controlled. SARS-CoV-2 is a single-stranded RNA virus with 4 main structural proteins, the spike (S) glycoprotein, the small envelope (E) the glycoprotein, the membrane (M) glycoprotein as well as the nucleocapsid (N) protein. Current knowledge about the virus shows that it uses its spike protein to invade host cells, mainly the alveolar epithelial cells. The the lung is the most targeted organ among many other organs like the heart, small intestine, and kidneys that are vulnerable to SARS-CoV-2 infection. The COVID-19 is known to be mild in most cases, but in some cases, it can be severe or even fatal. In the severe cases, acute respiratory distress syndrome was reported, and the the capability of SARS-CoV-2 to infect many organs can lead to multiorgan failure and death. SARS-CoV-2 invasion induces several immune responses that could be efficient for infection clearance in mild cases, while in severe cases, the immune response dysfunctions can even contribute to the disease aggravation. Neither the the pathogenic mechanism by which SARS-CoV-2 infects host cells, nor the host immune response to its infection have been fully understood, hence further studies are needed to give further evidence about these two phenomena. Keywords: COVID-19, SARS-CoV-2, Coronavirus, Structural proteins, Immune response.

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The Function of the PRRSV–Host Interactions and Their Effects on Viral Replication and Propagation in Antiviral Strategies

Vaccines ◽

10.3390/vaccines9040364 ◽

2021 ◽

Vol 9 (4) ◽

pp. 364

Author(s):

Jun Ma ◽

Lulu Ma ◽

Meiting Yang ◽

Wei Wu ◽

Wenhai Feng ◽

...

Keyword(s):

Immune Response ◽

Molecular Mechanisms ◽

Immune Escape ◽

Rna Virus ◽

Economic Losses ◽

Respiratory Syndrome Virus ◽

Swine Industry ◽

Live Virus ◽

Virus Challenge ◽

Host Interactions

Porcine reproductive and respiratory syndrome virus (PRRSV) affects the global swine industry and causes disastrous economic losses each year. The genome of PRRSV is an enveloped single-stranded positive-sense RNA of approximately 15 kb. The PRRSV replicates primarily in alveolar macrophages of pig lungs and lymphatic organs and causes reproductive problems in sows and respiratory symptoms in piglets. To date, studies on how PRRSV survives in the host, the host immune response against viral infections, and pathogenesis, have been reported. PRRSV vaccines have been developed, including inactive virus, modified live virus, attenuated live vaccine, DNA vaccine, and immune adjuvant vaccines. However, there are certain problems with the durability and effectiveness of the licensed vaccines. Moreover, the high variability and fast-evolving populations of this RNA virus challenge the design of PRRSV vaccines, and thus effective vaccines against PRRSV have not been developed successfully. As is well known, viruses interact with the host to escape the host’s immune response and then replicate and propagate in the host, which is the key to virus survival. Here, we review the complex network and the mechanism of PRRSV–host interactions in the processes of virus infection. It is critical to develop novel antiviral strategies against PRRSV by studying these host–virus interactions and structures to better understand the molecular mechanisms of PRRSV immune escape.

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Innate Immunity Evasion Strategies of Highly Pathogenic Coronaviruses: SARS-CoV, MERS-CoV, and SARS-CoV-2

Frontiers in Microbiology ◽

10.3389/fmicb.2021.770656 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jin-Yan Li ◽

Zhi-Jian Zhou ◽

Qiong Wang ◽

Qing-Nan He ◽

Ming-Yi Zhao ◽

...

Keyword(s):

Immune Response ◽

Pattern Recognition ◽

Current Knowledge ◽

Viral Pathogenesis ◽

Host Cells ◽

Highly Pathogenic ◽

Cellular Processes ◽

Antiviral Therapies ◽

The Past ◽

Human Coronaviruses

In the past two decades, coronavirus (CoV) has emerged frequently in the population. Three CoVs (SARS-CoV, MERS-CoV, SARS-CoV-2) have been identified as highly pathogenic human coronaviruses (HP-hCoVs). Particularly, the ongoing COVID-19 pandemic caused by SARS-CoV-2 warns that HP-hCoVs present a high risk to human health. Like other viruses, HP-hCoVs interact with their host cells in sophisticated manners for infection and pathogenesis. Here, we reviewed the current knowledge about the interference of HP-hCoVs in multiple cellular processes and their impacts on viral infection. HP-hCoVs employed various strategies to suppress and evade from immune response, including shielding viral RNA from recognition by pattern recognition receptors (PRRs), impairing IFN-I production, blocking the downstream pathways of IFN-I, and other evasion strategies. This summary provides a comprehensive view of the interplay between HP-hCoVs and the host cells, which is helpful to understand the mechanism of viral pathogenesis and develop antiviral therapies.

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The Multifaceted Roles of Autophagy in Flavivirus-Host Interactions

International Journal of Molecular Sciences ◽

10.3390/ijms19123940 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3940 ◽

Cited By ~ 19

Author(s):

Po-Yuan Ke

Keyword(s):

Stress Responses ◽

Current Knowledge ◽

Life Cycles ◽

Host Cells ◽

Human Diseases ◽

Organelle Biogenesis ◽

Host Interactions ◽

Evolutionarily Conserved ◽

Virus West Nile ◽

Flavivirus Infection

Autophagy is an evolutionarily conserved cellular process in which intracellular components are eliminated via lysosomal degradation to supply nutrients for organelle biogenesis and metabolic homeostasis. Flavivirus infections underlie multiple human diseases and thus exert an immense burden on public health worldwide. Mounting evidence indicates that host autophagy is subverted to modulate the life cycles of flaviviruses, such as hepatitis C virus, dengue virus, Japanese encephalitis virus, West Nile virus and Zika virus. The diverse interplay between autophagy and flavivirus infection not only regulates viral growth in host cells but also counteracts host stress responses induced by viral infection. In this review, we summarize the current knowledge on the role of autophagy in the flavivirus life cycle. We also discuss the impacts of virus-induced autophagy on the pathogeneses of flavivirus-associated diseases and the potential use of autophagy as a therapeutic target for curing flavivirus infections and related human diseases.

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Extracellular Vesicles in Viral Spread and Antiviral Response

Viruses ◽

10.3390/v12060623 ◽

2020 ◽

Vol 12 (6) ◽

pp. 623 ◽

Cited By ~ 5

Author(s):

Raquel Bello-Morales ◽

Inés Ripa ◽

José Antonio López-Guerrero

Keyword(s):

Immune Response ◽

Extracellular Vesicles ◽

Current Knowledge ◽

Host Immune Response ◽

Host Cells ◽

Viral Spread ◽

Viral Responses ◽

Hsv 1

Viral spread by both enveloped and non-enveloped viruses may be mediated by extracellular vesicles (EVs), including microvesicles (MVs) and exosomes. These secreted vesicles have been demonstrated to be an efficient mechanism that viruses can use to enter host cells, enhance spread or evade the host immune response. However, the complex interplay between viruses and EVs gives rise to antagonistic biological tasks—to benefit the viruses, enhancing infection and interfering with the immune system or to benefit the host, by mediating anti-viral responses. Exosomes from cells infected with herpes simplex type 1 (HSV-1) may transport viral and host transcripts, proteins and innate immune components. This virus may also use MVs to expand its tropism and evade the host immune response. This review aims to describe the current knowledge about EVs and their participation in viral infection, with a specific focus on the role of exosomes and MVs in herpesvirus infections, particularly that of HSV-1.

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Modulation of the Host Immune Response by Schistosome Egg-Secreted Proteins Is a Critical Avenue of Host–Parasite Communication

Pathogens ◽

10.3390/pathogens10070863 ◽

2021 ◽

Vol 10 (7) ◽

pp. 863

Author(s):

Jack P. Carson ◽

Geoffrey N. Gobert

Keyword(s):

Immune Response ◽

Current Knowledge ◽

Host Immune Response ◽

Egg Laying ◽

Host Cells ◽

Future Application ◽

Mammalian Host ◽

Immunomodulatory Activity ◽

Host Immune System

During a schistosome infection, the interactions that occur between the mammalian host and the parasite change rapidly once egg laying begins. Both juvenile and adult schistosomes adapt to indefinitely avoid the host immune system. In contrast, the survival of eggs relies on quickly traversing from the host. Following the commencement of egg laying, the host immune response undergoes a shift from a type 1 helper (Th1) inflammatory response to a type 2 helper (Th2) granulomatous response. This change is driven by immunomodulatory proteins within the egg excretory/secretory products (ESPs), which interact with host cells and alter their behaviour to promote egg translocation. However, in parallel, these ESPs also provoke the development of chronic schistosomiasis pathology. Recent studies using high-throughput proteomics have begun to characterise the components of schistosome egg ESPs, particularly those of Schistosoma mansoni, S. japonicum and S. haematobium. Future application of this knowledge may lead to the identification of proteins with novel immunomodulatory activity or pathological importance. However, efforts in this area are limited by a lack of in situ or in vivo functional characterisation of these proteins. This review will highlight the current knowledge of the content and demonstrated functions of schistosome egg ESPs.

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Roles of the Non-Structural Proteins of Influenza A Virus

Pathogens ◽

10.3390/pathogens9100812 ◽

2020 ◽

Vol 9 (10) ◽

pp. 812

Author(s):

Wenzhuo Hao ◽

Lingyan Wang ◽

Shitao Li

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Rna Virus ◽

Critical Role ◽

Viral Proteins ◽

Host Cells ◽

Structural Proteins ◽

Host Interactions ◽

New Findings ◽

Seasonal Epidemics

Influenza A virus (IAV) is a segmented, negative single-stranded RNA virus that causes seasonal epidemics and has a potential for pandemics. Several viral proteins are not packed in the IAV viral particle and only expressed in the infected host cells. These proteins are named non-structural proteins (NSPs), including NS1, PB1-F2 and PA-X. They play a versatile role in the viral life cycle by modulating viral replication and transcription. More importantly, they also play a critical role in the evasion of the surveillance of host defense and viral pathogenicity by inducing apoptosis, perturbing innate immunity, and exacerbating inflammation. Here, we review the recent advances of these NSPs and how the new findings deepen our understanding of IAV–host interactions and viral pathogenesis.

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RNA virus-encoded microRNAs: biogenesis, functions and perspectives on application

ExRNA ◽

10.1186/s41544-020-00056-z ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Shoubin Zhan ◽

Yanbo Wang ◽

Xi Chen

Keyword(s):

Current Knowledge ◽

Rna Virus ◽

Noncoding Rnas ◽

Biological Functions ◽

Dna Viruses ◽

Regulate Gene Expression ◽

Host Interactions ◽

Small Noncoding Rnas ◽

Genome Wide ◽

Posttranscriptional Level

Abstract MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression at the posttranscriptional level and play a crucial role in development and many diseases. The discovery of miRNAs has greatly expanded our understanding of the intricate scenario of genome-wide regulation. Over the last two decades, hundreds of virus-encoded miRNAs have been identified, most of which are from DNA viruses. Although the number of reported RNA virus-derived miRNAs is increasing, current knowledge of their roles in physiological and pathological processes has remained lacking. In this review, we discuss the biogenesis and biological functions of RNA virus- encoded miRNAs and their proposed roles in virus-host interactions and further underscore their potential value in the diagnosis and treatment of viral diseases.

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Sensing of cytoplasmic chromatin by cGAS activates innate immune response in SARS-CoV-2 infection

10.21203/rs.3.rs-235742/v1 ◽

2021 ◽

Author(s):

Zhuo Zhou ◽

Xinyi Zhang ◽

Xiaobo Lei ◽

Xia Xiao ◽

Tao Jiao ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Cell Fusion ◽

Innate Immune Response ◽

Rna Virus ◽

Cellular Level ◽

Innate Immune ◽

Host Cells ◽

Host Immune System ◽

Sting Pathway

Abstract The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection remain to be determined. Here, we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway. SARS-CoV-2 infection induces the cellular level of 2'3'-cGAMP associated with STING activation. cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection. We further demonstrate that the expression of spike protein from SARS-CoV-2 and ACE2 from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion. Furthermore, cytoplasmic chromatin-cGAS-STING pathway, but not MAVS mediated viral RNA sensing pathway, contributes to interferon and pro-inflammatory gene expression upon cell fusion. Finally, we show that cGAS is required for host antiviral responses against SARS-CoV-2, and a STING-activating compound potently inhibits viral replication. Together, our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection, mediated by cytoplasmic chromatin from the infected cells. Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19. In addition, these findings extend our knowledge in host defense against viral infection by showing that host cells’ self-nucleic acids can be employed as a “danger signal” to alarm the immune system.

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Sensing of cytoplasmic chromatin by cGAS activates innate immune response in SARS-CoV-2 infection

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00800-3 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Zhuo Zhou ◽

Xinyi Zhang ◽

Xiaobo Lei ◽

Xia Xiao ◽

Tao Jiao ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Cell Fusion ◽

Innate Immune Response ◽

Rna Virus ◽

Cellular Level ◽

Innate Immune ◽

Host Cells ◽

Host Immune System ◽

Sting Pathway

AbstractThe global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved. Here, we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway. SARS-CoV-2 infection induces the cellular level of 2′3′-cGAMP associated with STING activation. cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection. We further demonstrate that the expression of spike protein from SARS-CoV-2 and ACE2 from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion. Furthermore, cytoplasmic chromatin-cGAS-STING pathway, but not MAVS-mediated viral RNA sensing pathway, contributes to interferon and pro-inflammatory gene expression upon cell fusion. Finally, we show that cGAS is required for host antiviral responses against SARS-CoV-2, and a STING-activating compound potently inhibits viral replication. Together, our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection, mediated by cytoplasmic chromatin from the infected cells. Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19. In addition, these findings extend our knowledge in host defense against viral infection by showing that host cells’ self-nucleic acids can be employed as a “danger signal” to alarm the immune system.

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