Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 26
Filter
1.
Int J Mol Sci ; 22(14)2021 Jul 06.
Article in English | MEDLINE | ID: covidwho-1485149

ABSTRACT

Chronic neurodegenerative diseases are complex, and their pathogenesis is uncertain. Alzheimer's disease (AD) is a neurodegenerative brain alteration that is responsible for most dementia cases in the elderly. AD etiology is still uncertain; however, chronic neuroinflammation is a constant component of brain pathology. Infections have been associated with several neurological diseases and viruses of the Herpes family appear to be a probable cause of AD neurodegenerative alterations. Several different factors may contribute to the AD clinical progression. Exogeneous viruses or other microbes and environmental pollutants may directly induce neurodegeneration by activating brain inflammation. In this paper, we suggest that exogeneous brain insults may also activate retrotransposons and silent human endogenous retroviruses (HERVs). The initial inflammation of small brain areas induced by virus infections or other brain insults may activate HERV dis-regulation that contributes to neurodegenerative mechanisms. Chronic HERV activation in turn may cause progressive neurodegeneration that thereafter merges in cognitive impairment and dementia in genetically susceptible people. Specific treatment for exogenous end endogenous pathogens and decreasing pollutant exposure may show beneficial effect in early intervention protocol to prevent the progression of cognitive deterioration in the elderly.


Subject(s)
Alzheimer Disease/pathology , Alzheimer Disease/virology , Brain/pathology , Brain/virology , Endogenous Retroviruses/pathogenicity , Virus Diseases/pathology , Virus Diseases/virology , Animals , Cognition Disorders/pathology , Cognition Disorders/virology , Encephalitis/pathology , Encephalitis/virology , Humans
2.
Int J Mol Sci ; 22(20)2021 Oct 12.
Article in English | MEDLINE | ID: covidwho-1463715

ABSTRACT

G-quadruplexes (G4s) are noncanonical nucleic acid structures involved in the regulation of key cellular processes, such as transcription and replication. Since their discovery, G4s have been mainly investigated for their role in cancer and as targets in anticancer therapy. More recently, exploration of the presence and role of G4s in viral genomes has led to the discovery of G4-regulated key viral pathways. In this context, employment of selective G4 ligands has helped to understand the complexity of G4-mediated mechanisms in the viral life cycle, and highlighted the possibility to target viral G4s as an emerging antiviral approach. Research in this field is growing at a fast pace, providing increasing evidence of the antiviral activity of old and new G4 ligands. This review aims to provide a punctual update on the literature on G4 ligands exploited in virology. Different classes of G4 binders are described, with emphasis on possible antiviral applications in emerging diseases, such as the current COVID-19 pandemic. Strengths and weaknesses of G4 targeting in viruses are discussed.


Subject(s)
Antiviral Agents/chemistry , G-Quadruplexes , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , DNA, Viral/chemistry , DNA, Viral/metabolism , Humans , Ligands , MicroRNAs/antagonists & inhibitors , MicroRNAs/metabolism , RNA, Viral/chemistry , RNA, Viral/metabolism , SARS-CoV-2/isolation & purification , Virus Diseases/drug therapy , Virus Diseases/pathology
3.
J Clin Invest ; 131(11)2021 06 01.
Article in English | MEDLINE | ID: covidwho-1448082

ABSTRACT

First administered to a human subject as a tuberculosis (TB) vaccine on July 18, 1921, Bacillus Calmette-Guérin (BCG) has a long history of use for the prevention of TB and later the immunotherapy of bladder cancer. For TB prevention, BCG is given to infants born globally across over 180 countries and has been in use since the late 1920s. With about 352 million BCG doses procured annually and tens of billions of doses having been administered over the past century, it is estimated to be the most widely used vaccine in human history. While its roles for TB prevention and bladder cancer immunotherapy are widely appreciated, over the past century, BCG has been also studied for nontraditional purposes, which include (a) prevention of viral infections and nontuberculous mycobacterial infections, (b) cancer immunotherapy aside from bladder cancer, and (c) immunologic diseases, including multiple sclerosis, type 1 diabetes, and atopic diseases. The basis for these heterologous effects lies in the ability of BCG to alter immunologic set points via heterologous T cell immunity, as well as epigenetic and metabolomic changes in innate immune cells, a process called "trained immunity." In this Review, we provide an overview of what is known regarding the trained immunity mechanism of heterologous protection, and we describe the current knowledge base for these nontraditional uses of BCG.


Subject(s)
Diabetes Mellitus, Type 1/therapy , Immunity, Cellular , Multiple Sclerosis/therapy , Mycobacterium bovis/immunology , T-Lymphocytes/immunology , Urinary Bladder Neoplasms/therapy , Virus Diseases/therapy , Animals , Diabetes Mellitus, Type 1/history , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/pathology , History, 20th Century , History, 21st Century , Humans , Multiple Sclerosis/history , Multiple Sclerosis/immunology , Multiple Sclerosis/pathology , Mycobacterium Infections, Nontuberculous/history , Mycobacterium Infections, Nontuberculous/immunology , Mycobacterium Infections, Nontuberculous/pathology , Mycobacterium Infections, Nontuberculous/prevention & control , Tuberculosis/history , Tuberculosis/immunology , Tuberculosis/prevention & control , Urinary Bladder Neoplasms/history , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/pathology , Virus Diseases/history , Virus Diseases/immunology , Virus Diseases/pathology
4.
Biochim Biophys Acta Rev Cancer ; 1876(2): 188622, 2021 12.
Article in English | MEDLINE | ID: covidwho-1377662

ABSTRACT

Since the identification of the first human oncogenic virus in 1964, viruses have been studied for their potential role in aiding the development of cancer. Through the modulation of cellular pathways associated with proliferation, immortalization, and inflammation, viral proteins can mimic the effect of driver mutations and contribute to transformation. Aside from the modulation of signaling pathways, the insertion of viral DNA into the host genome and the deregulation of cellular miRNAs represent two additional mechanisms implicated in viral oncogenesis. In this review, we will discuss the role of twelve different viruses on cancer development and how these viruses utilize the abovementioned mechanisms to influence oncogenesis. The identification of specific mechanisms behind viral transformation of human cells could further elucidate the process behind cancer development.


Subject(s)
Cell Transformation, Neoplastic/genetics , Neoplasms/etiology , Neoplasms/virology , Virus Diseases/complications , Humans , Virus Diseases/pathology
5.
Int J Mol Sci ; 22(17)2021 Aug 29.
Article in English | MEDLINE | ID: covidwho-1374429

ABSTRACT

Heat shock proteins (HSPs) are a large group of chaperones found in most eukaryotes and bacteria. They are responsible for the correct protein folding, protection of the cell against stressors, presenting immune and inflammatory cytokines; furthermore, they are important factors in regulating cell differentiation, survival and death. Although the biological function of HSPs is to maintain cell homeostasis, some of them can be used by viruses both to fold their proteins and increase the chances of survival in unfavorable host conditions. Folding viral proteins as well as replicating many different viruses are carried out by, among others, proteins from the HSP70 and HSP90 families. In some cases, the HSP70 family proteins directly interact with viral polymerase to enhance viral replication or they can facilitate the formation of a viral replication complex and/or maintain the stability of complex proteins. It is known that HSP90 is important for the expression of viral genes at both the transcriptional and the translational levels. Both of these HSPs can form a complex with HSP90 and, consequently, facilitate the entry of the virus into the cell. Current studies have shown the biological significance of HSPs in the course of infection SARS-CoV-2. A comprehensive understanding of chaperone use during viral infection will provide new insight into viral replication mechanisms and therapeutic potential. The aim of this study is to describe the molecular basis of HSP70 and HSP90 participation in some viral infections and the potential use of these proteins in antiviral therapy.


Subject(s)
HSP70 Heat-Shock Proteins/metabolism , HSP90 Heat-Shock Proteins/metabolism , Virus Diseases/pathology , COVID-19/metabolism , COVID-19/pathology , COVID-19/virology , DNA Viruses/physiology , Humans , Protein Isoforms/metabolism , RNA Viruses/physiology , SARS-CoV-2/isolation & purification , Virus Diseases/metabolism , Virus Diseases/virology
6.
Int J Mol Sci ; 22(13)2021 Jun 29.
Article in English | MEDLINE | ID: covidwho-1304667

ABSTRACT

Amyloid beta (Aß)-induced abnormal neuroinflammation is recognized as a major pathological feature of Alzheimer's disease (AD), which results in memory impairment. Research exploring low-grade systemic inflammation and its impact on the development and progression of neurodegenerative disease has increased. A particular research focus has been whether systemic inflammation arises only as a secondary effect of disease, or it is also a cause of pathology. The inflammasomes, and more specifically the NLRP3 inflammasome, are crucial components of the innate immune system and are usually activated in response to infection or tissue damage. Although inflammasome activation plays critical roles against various pathogens in host defense, overactivation of inflammasome contributes to the pathogenesis of inflammatory diseases, including acute central nervous system (CNS) injuries and chronic neurodegenerative diseases, such as AD. This review summarizes the current literature on the role of the NLRP3 inflammasome in the pathogenesis of AD, and its involvement in infections, particularly SARS-CoV-2. NLRP3 might represent the crossroad between the hypothesized neurodegeneration and the primary COVID-19 infection.


Subject(s)
Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Alzheimer Disease/metabolism , Animals , Coronavirus/pathogenicity , Humans , Immunity, Innate , Microglia/metabolism , Virus Diseases/immunology , Virus Diseases/pathology
7.
Int J Mol Sci ; 22(13)2021 Jun 29.
Article in English | MEDLINE | ID: covidwho-1295856

ABSTRACT

Amyloid beta (Aß)-induced abnormal neuroinflammation is recognized as a major pathological feature of Alzheimer's disease (AD), which results in memory impairment. Research exploring low-grade systemic inflammation and its impact on the development and progression of neurodegenerative disease has increased. A particular research focus has been whether systemic inflammation arises only as a secondary effect of disease, or it is also a cause of pathology. The inflammasomes, and more specifically the NLRP3 inflammasome, are crucial components of the innate immune system and are usually activated in response to infection or tissue damage. Although inflammasome activation plays critical roles against various pathogens in host defense, overactivation of inflammasome contributes to the pathogenesis of inflammatory diseases, including acute central nervous system (CNS) injuries and chronic neurodegenerative diseases, such as AD. This review summarizes the current literature on the role of the NLRP3 inflammasome in the pathogenesis of AD, and its involvement in infections, particularly SARS-CoV-2. NLRP3 might represent the crossroad between the hypothesized neurodegeneration and the primary COVID-19 infection.


Subject(s)
Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Alzheimer Disease/metabolism , Animals , Coronavirus/pathogenicity , Humans , Immunity, Innate , Microglia/metabolism , Virus Diseases/immunology , Virus Diseases/pathology
8.
Front Immunol ; 12: 687534, 2021.
Article in English | MEDLINE | ID: covidwho-1295639

ABSTRACT

The clinical significance of antiphospholipid antibodies (aPL) in the context of infections has attracted attention since their first discovery in patients with syphilis. In fact, the recognition of aPL in patients with infections has been described in parallel to the understating of the syndrome. Since the first description of aPL-positive tests in three patients with COVID-19 diagnosed in January 2020 in Wuhan, China, a large number of studies took part in the ongoing debate on SARS-2-Cov 2 induced coagulopathy, and many following reports speculated a potential role for aPL. In order to get further insights on the effective role of detectable aPL in the pro-thrombotic status observed in COVID-19 patients, we performed an observational age-sex controlled study to compare the aPL profile of hospitalized patients with COVID with those observed in a) patients with thrombotic APS and b) patients with cultural/serologically-proved infections. Our data showed positive aPL testing in about half of the patients (53%) with COVID-19 and patients with other viral/bacterial infections (49%). However, aPL profile was different when comparing patients with overt APS and patients with aPL detected in the contest of infections. Caution is therefore required in the interpretation and generalization of the role of aPL s in the management of patients with COVID-19. Before introducing aPL testing as a part of the routine testing in patients with COVID-19, larger well-designed clinical studies are required. While the pro-thrombotic status in patients with COVID-19 is now unquestionable, different mechanisms other than aPL should be further investigated.


Subject(s)
Antibodies, Antiphospholipid/blood , Antiphospholipid Syndrome/pathology , Bacterial Infections/pathology , COVID-19/pathology , Disseminated Intravascular Coagulation/pathology , Virus Diseases/pathology , Aged , Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/immunology , Bacterial Infections/complications , COVID-19/complications , COVID-19/immunology , Disseminated Intravascular Coagulation/virology , Female , Humans , Male , SARS-CoV-2/immunology , Virus Diseases/complications
9.
Int J Mol Sci ; 22(13)2021 Jun 28.
Article in English | MEDLINE | ID: covidwho-1288899

ABSTRACT

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and vaccines against viral infections. Besides the specific physiological properties of the respiratory system, there is a significant demand for utilizing nano-designs in the production of vaccines or antiviral agents for airway-localized administration. SARS-CoV-2, as an immediate example of respiratory viruses, is an enveloped, positive-sense, single-stranded RNA virus belonging to the coronaviridae family. COVID-19 can lead to acute respiratory distress syndrome, similarly to other members of the coronaviridae. Hence, reviewing the current and past emerging nanotechnology-based medications on similar respiratory viral diseases can identify pathways towards generating novel SARS-CoV-2 nanotherapeutics and/or nano-vaccines.


Subject(s)
Antiviral Agents/chemistry , Drug Carriers/chemistry , Nanomedicine , Respiratory Tract Infections/pathology , Viral Vaccines/chemistry , Virus Diseases/pathology , Antiviral Agents/therapeutic use , COVID-19/immunology , COVID-19/pathology , COVID-19/therapy , COVID-19/virology , Humans , Immune System/metabolism , Respiratory Tract Infections/therapy , Respiratory Tract Infections/virology , SARS-CoV-2/isolation & purification , Viral Vaccines/administration & dosage , Viral Vaccines/immunology , Virus Diseases/immunology , Virus Diseases/prevention & control , Virus Diseases/therapy
10.
Int J Mol Sci ; 22(12)2021 Jun 18.
Article in English | MEDLINE | ID: covidwho-1273463

ABSTRACT

Heparan sulfate proteoglycans (HSPGs) encompass a group of glycoproteins composed of unbranched negatively charged heparan sulfate (HS) chains covalently attached to a core protein. The complex HSPG biosynthetic machinery generates an extraordinary structural variety of HS chains that enable them to bind a plethora of ligands, including growth factors, morphogens, cytokines, chemokines, enzymes, matrix proteins, and bacterial and viral pathogens. These interactions translate into key regulatory activity of HSPGs on a wide range of cellular processes such as receptor activation and signaling, cytoskeleton assembly, extracellular matrix remodeling, endocytosis, cell-cell crosstalk, and others. Due to their ubiquitous expression within tissues and their large functional repertoire, HSPGs are involved in many physiopathological processes; thus, they have emerged as valuable targets for the therapy of many human diseases. Among their functions, HSPGs assist many viruses in invading host cells at various steps of their life cycle. Viruses utilize HSPGs for the attachment to the host cell, internalization, intracellular trafficking, egress, and spread. Recently, HSPG involvement in the pathogenesis of SARS-CoV-2 infection has been established. Here, we summarize the current knowledge on the molecular mechanisms underlying HSPG/SARS-CoV-2 interaction and downstream effects, and we provide an overview of the HSPG-based therapeutic strategies that could be used to combat such a fearsome virus.


Subject(s)
COVID-19/pathology , Heparan Sulfate Proteoglycans/metabolism , SARS-CoV-2/metabolism , COVID-19/drug therapy , COVID-19/virology , Heparan Sulfate Proteoglycans/chemistry , Heparin, Low-Molecular-Weight/chemistry , Heparin, Low-Molecular-Weight/metabolism , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/metabolism , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Sulfotransferases/metabolism , Virus Diseases/drug therapy , Virus Diseases/pathology , Virus Diseases/virology , Virus Internalization/drug effects
11.
ACS Appl Mater Interfaces ; 13(18): 20995-21006, 2021 May 12.
Article in English | MEDLINE | ID: covidwho-1209173

ABSTRACT

COVID-19 has been diffusely pandemic around the world, characterized by massive morbidity and mortality. One of the remarkable threats associated with mortality may be the uncontrolled inflammatory processes, which were induced by SARS-CoV-2 in infected patients. As there are no specific drugs, exploiting safe and effective treatment strategies is an instant requirement to dwindle viral damage and relieve extreme inflammation simultaneously. Here, highly biocompatible glycyrrhizic acid (GA) nanoparticles (GANPs) were synthesized based on GA. In vitro investigations revealed that GANPs inhibit the proliferation of the murine coronavirus MHV-A59 and reduce proinflammatory cytokine production caused by MHV-A59 or the N protein of SARS-CoV-2. In an MHV-A59-induced surrogate mouse model of COVID-19, GANPs specifically target areas with severe inflammation, such as the lungs, which appeared to improve the accumulation of GANPs and enhance the effectiveness of the treatment. Further, GANPs also exert antiviral and anti-inflammatory effects, relieving organ damage and conferring a significant survival advantage to infected mice. Such a novel therapeutic agent can be readily manufactured into feasible treatment for COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Glycyrrhizic Acid/therapeutic use , Inflammation/drug therapy , Nanoparticles/therapeutic use , Virus Diseases/drug therapy , Animals , Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , Antioxidants/therapeutic use , Antiviral Agents/chemistry , COVID-19/drug therapy , Coronavirus Nucleocapsid Proteins/pharmacology , Cytokines/metabolism , Female , Glycyrrhizic Acid/chemistry , Humans , Liver/pathology , Lung/pathology , Mice , Mice, Inbred BALB C , Murine hepatitis virus/drug effects , Nanoparticles/chemistry , Phosphoproteins/pharmacology , RAW 264.7 Cells , SARS-CoV-2/chemistry , THP-1 Cells , Viral Load/drug effects , Virus Diseases/pathology , Virus Replication/drug effects
12.
Int J Mol Sci ; 22(4)2021 Feb 16.
Article in English | MEDLINE | ID: covidwho-1139186

ABSTRACT

Bcl-xL represents a family of proteins responsible for the regulation of the intrinsic apoptosis pathway. Due to its anti-apoptotic activity, Bcl-xL co-determines the viability of various virally infected cells. Their survival may determine the effectiveness of viral replication and spread, dynamics of systemic infection, and viral pathogenesis. In this paper, we have reviewed the role of Bcl-xL in the context of host infection by eight different RNA and DNA viruses: hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), influenza A virus (IAV), Epstein-Barr virus (EBV), human T-lymphotropic virus type-1 (HTLV-1), Maraba virus (MRBV), Schmallenberg virus (SBV) and coronavirus (CoV). We have described an influence of viral infection on the intracellular level of Bcl-xL and discussed the impact of Bcl-xL-dependent cell survival control on infection-accompanying pathogenic events such as tissue damage or oncogenesis. We have also presented anti-viral treatment strategies based on the pharmacological regulation of Bcl-xL expression or activity.


Subject(s)
Apoptosis , Virus Diseases/metabolism , bcl-X Protein/metabolism , Animals , Cell Survival , Host-Pathogen Interactions , Humans , Virus Diseases/pathology , Virus Replication , Viruses/metabolism , bcl-X Protein/analysis
13.
Adv Sci (Weinh) ; 8(7): 2003895, 2021 04.
Article in English | MEDLINE | ID: covidwho-1103262

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that has quickly and deeply affected the world, with over 60 million confirmed cases. There has been a great effort worldwide to contain the virus and to search for an effective treatment for patients who become critically ill with COVID-19. A promising therapeutic compound currently undergoing clinical trials for COVID-19 is nitric oxide (NO), which is a free radical that has been previously reported to inhibit the replication of several DNA and RNA viruses, including coronaviruses. Although NO has potent antiviral activity, it has a complex role in the immunological host responses to viral infections, i.e., it can be essential for pathogen control or detrimental for the host, depending on its concentration and the type of virus. In this Essay, the antiviral role of NO against SARS-CoV, SARS-CoV-2, and other human viruses is highlighted, current development of NO-based therapies used in the clinic is summarized, existing challenges are discussed and possible further developments of NO to fight viral infections are suggested.


Subject(s)
Antiviral Agents/therapeutic use , Nitric Oxide/therapeutic use , Virus Diseases/drug therapy , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Clinical Trials as Topic , Humans , Nitric Oxide/pharmacology , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Virus Diseases/pathology , Virus Replication/drug effects
14.
Sci Rep ; 11(1): 1793, 2021 01 19.
Article in English | MEDLINE | ID: covidwho-1065942

ABSTRACT

COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and other respiratory viral (non-CoV-2-RV) infections are associated with thrombotic complications. The differences in prothrombotic potential between SARS-CoV-2 and non-CoV-2-RV have not been well characterised. We compared the thrombotic rates between these two groups of patients directly and further delved into their coagulation profiles. In this single-center, retrospective cohort study, all consecutive COVID-19 and non-CoV-2-RV patients admitted between January 15th and April 10th 2020 were included. Coagulation parameters studied were prothrombin time and activated partial thromboplastin time and its associated clot waveform analysis (CWA) parameter, min1, min2 and max2. In the COVID-19 (n = 181) group there were two (1.0 event/1000-hospital-days) myocardial infarction events while one (1.8 event/1000-hospital-day) was reported in the non-CoV-2-RV (n = 165) group. These events occurred in patients who were severely ill. There were no venous thrombotic events. Coagulation parameters did not differ throughout the course of mild COVID-19. However, CWA parameters were significantly higher in severe COVID-19 compared with mild disease, suggesting hypercoagulability (min1: 6.48%/s vs 5.05%/s, P < 0.001; min2: 0.92%/s2 vs 0.74%/s2, P = 0.033). In conclusion, the thrombotic rates were low and did not differ between COVID-19 and non-CoV-2-RV patients. The hypercoagulability in COVID-19 is a highly dynamic process with the highest risk occurring when patients were most severely ill. Such changes in haemostasis could be detected by CWA. In our population, a more individualized thromboprophylaxis approach, considering clinical and laboratory factors, is preferred over universal pharmacological thromboprophylaxis for all hospitalized COVID-19 patients and such personalized approach warrants further research.


Subject(s)
COVID-19/pathology , Thrombophilia/diagnosis , Virus Diseases/pathology , Adult , COVID-19/complications , COVID-19/virology , Female , Humans , Male , Myocardial Infarction/complications , Myocardial Infarction/diagnosis , Partial Thromboplastin Time , Prothrombin Time , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Thrombophilia/complications , Virus Diseases/complications
15.
J Virol ; 95(2)2020 12 22.
Article in English | MEDLINE | ID: covidwho-1041542

ABSTRACT

Viral infections during pregnancy lead to a spectrum of maternal and fetal outcomes, ranging from asymptomatic disease to more critical conditions presenting with severe maternal morbidity, stillbirth, preterm birth, intrauterine growth restriction, and fetal congenital anomalies, either apparent at birth or later in life. In this article, we review the pathogenesis of several viral infections that are particularly relevant in the context of pregnancy and intrauterine inflammation. Understanding the diverse mechanisms employed by viral pathogens as well as the repertoire of immune responses induced in the mother may help to establish novel therapeutic options to attenuate changes in the maternal-fetal interface and prevent adverse pregnancy outcomes.


Subject(s)
Inflammation/immunology , Pregnancy Complications, Infectious/virology , Virus Diseases/virology , Viruses/pathogenicity , Female , Humans , Infant, Newborn , Placenta/immunology , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/pathology , Pregnancy Outcome , Virus Diseases/immunology , Virus Diseases/pathology , Viruses/classification , Viruses/immunology
16.
ACS Chem Neurosci ; 11(24): 4012-4016, 2020 12 16.
Article in English | MEDLINE | ID: covidwho-983572

ABSTRACT

The current pandemic of coronavirus disease 2019 (COVID-19) has gained increased attention in the neuroscience community, especially taking into account the neuroinvasive potential of its causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the impact of its infection on the structure and function of the brain. Apart from the neurotropic properties of SARS-CoV-2, it is likewise important the observation that virus infection may perturb specific cellular processes that are believed to play an important role in the pathogenesis of diverse neurological disorders, particularly in Parkinson's disease (PD). In this scenario, viral infection-induced colon inflammation, gut microbial imbalance, and α-synuclein upregulation are of particular interest with regard to the interplay between the gastrointestinal tract and the central nervous system (microbiome-gut-brain axis). In this Perspective, we present a critical view on the different hypotheses that are recently being raised by neuroscientists about the relationship between SARS-CoV-2 infection and long-lasting neurodegenerative disorders, opening the question of whether COVID-19 might represent a risk factor for the development of PD.


Subject(s)
Dysbiosis/virology , Neurodegenerative Diseases/virology , SARS-CoV-2/pathogenicity , Virus Diseases/virology , Brain/pathology , Brain/virology , Dysbiosis/complications , Gastrointestinal Microbiome/physiology , Humans , Neurodegenerative Diseases/pathology , Virus Diseases/complications , Virus Diseases/pathology
17.
Nat Commun ; 11(1): 6122, 2020 11 30.
Article in English | MEDLINE | ID: covidwho-952011

ABSTRACT

Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2 transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2 transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2 transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Disease Models, Animal , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Animals , Brain/immunology , Brain/pathology , Brain/virology , COVID-19/immunology , COVID-19/pathology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Disease Susceptibility , Genetic Predisposition to Disease , Keratin-18/genetics , Lung/immunology , Lung/pathology , Lung/virology , Mice , Mice, Transgenic , Mortality , Promoter Regions, Genetic/genetics , Respiratory Mucosa/immunology , Respiratory Mucosa/pathology , Respiratory Mucosa/virology , Virus Diseases/immunology , Virus Diseases/pathology
18.
Oxid Med Cell Longev ; 2020: 8893305, 2020.
Article in English | MEDLINE | ID: covidwho-949228

ABSTRACT

As an essential lipid, cholesterol is of great value in keeping cell homeostasis, being the precursor of bile acid and steroid hormones, and stabilizing membrane lipid rafts. As a kind of cholesterol metabolite produced by enzymatic or radical process, oxysterols have drawn much attention in the last decades. Among which, the role of 25-hydroxycholesterol (25-HC) in cholesterol and bile acid metabolism, antivirus process, and inflammatory response has been largely disclosed. This review is aimed at revealing these functions and underlying mechanisms of 25-HC.


Subject(s)
Hydroxycholesterols/metabolism , Lipid Metabolism , Virus Diseases/metabolism , Animals , Cell Survival , Humans , Inflammation/metabolism , Inflammation/pathology , Inflammation/virology , Membrane Microdomains/pathology , Membrane Microdomains/virology , Virus Diseases/pathology
19.
Microb Cell Fact ; 19(1): 217, 2020 Nov 26.
Article in English | MEDLINE | ID: covidwho-945212

ABSTRACT

All of humans and other mammalian species are colonized by some types of microorganisms such as bacteria, archaea, unicellular eukaryotes like fungi and protozoa, multicellular eukaryotes like helminths, and viruses, which in whole are called microbiota. These microorganisms have multiple different types of interaction with each other. A plethora of evidence suggests that they can regulate immune and digestive systems and also play roles in various diseases, such as mental, cardiovascular, metabolic and some skin diseases. In addition, they take-part in some current health problems like diabetes mellitus, obesity, cancers and infections. Viral infection is one of the most common and problematic health care issues, particularly in recent years that pandemics like SARS and COVID-19 caused a lot of financial and physical damage to the world. There are plenty of articles investigating the interaction between microbiota and infectious diseases. We focused on stimulatory to suppressive effects of microbiota on viral infections, hoping to find a solution to overcome this current pandemic. Then we reviewed mechanistically the effects of both microbiota and probiotics on most of the viruses. But unlike previous studies which concentrated on intestinal microbiota and infection, our focus is on respiratory system's microbiota and respiratory viral infection, bearing in mind that respiratory system is a proper entry site and residence for viruses, and whereby infection, can lead to asymptomatic, mild, self-limiting, severe or even fatal infection. Finally, we overgeneralize the effects of microbiota on COVID-19 infection. In addition, we reviewed the articles about effects of the microbiota on coronaviruses and suggest some new therapeutic measures.


Subject(s)
COVID-19/therapy , Microbiota , Virus Diseases/pathology , COVID-19/pathology , COVID-19/virology , Humans , Lung/metabolism , Lung/microbiology , Neoplasms/metabolism , Neoplasms/microbiology , Neoplasms/pathology , Nervous System/metabolism , Probiotics/administration & dosage , SARS-CoV-2/isolation & purification , Virus Diseases/metabolism , Virus Diseases/microbiology
20.
Cells ; 9(11)2020 11 07.
Article in English | MEDLINE | ID: covidwho-918180

ABSTRACT

Viruses exhibit an elegant simplicity, as they are so basic, but so frightening. Although only a few are life threatening, they have substantial implications for human health and the economy, as exemplified by the ongoing coronavirus pandemic. Viruses are rather small infectious agents found in all types of life forms, from animals and plants to prokaryotes and archaebacteria. They are obligate intracellular parasites, and as such, subvert many molecular and cellular processes of the host cell to ensure their own replication, amplification, and subsequent spread. This special issue addresses the cell biology of viral infections based on a collection of original research articles, communications, opinions, and reviews on various aspects of virus-host cell interactions. Together, these articles not only provide a glance into the latest research on the cell biology of viral infections, but also include novel technological developments.


Subject(s)
Virus Diseases/pathology , Animals , Betacoronavirus/physiology , Host-Pathogen Interactions , Humans , SARS-CoV-2 , Signal Transduction , Virus Diseases/metabolism , Virus Diseases/virology , Zika Virus/physiology
SELECTION OF CITATIONS
SEARCH DETAIL
...