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2.
J Med Virol ; 93(11): 6116-6123, 2021 11.
Article in English | MEDLINE | ID: covidwho-1349155

ABSTRACT

Virus invasion activates the host's innate immune response, inducing the production of numerous cytokines and interferons to eliminate pathogens. Except for viral DNA/RNA, viral proteins are also targets of pattern recognition receptors. Membrane-bound receptors such as Toll-like receptor (TLR)1, TLR2, TLR4, TLR6, and TLR10 relate to the recognition of viral proteins. Distinct TLRs perform both protective and detrimental roles for a specific virus. Here, we review viral proteins serving as pathogen-associated molecular patterns and their corresponding TLRs. These viruses are all enveloped, including respiratory syncytial virus, hepatitis C virus, measles virus, herpesvirus human immunodeficiency virus, and coronavirus, and can encode proteins to activate innate immunity in a TLR-dependent way. The TLR-viral protein relationship plays an important role in innate immunity activation. A detailed understanding of their pathways contributes to a novel direction for vaccine development.


Subject(s)
Immunity, Innate , Pathogen-Associated Molecular Pattern Molecules/metabolism , Toll-Like Receptors/immunology , Toll-Like Receptors/metabolism , Viral Proteins/metabolism , Virus Diseases/immunology , Viruses/immunology , Animals , HIV/immunology , HIV/metabolism , HIV/pathogenicity , Hepacivirus/immunology , Hepacivirus/metabolism , Hepacivirus/pathogenicity , Herpesviridae/immunology , Herpesviridae/metabolism , Herpesviridae/pathogenicity , Humans , Measles virus/immunology , Measles virus/metabolism , Measles virus/pathogenicity , Pathogen-Associated Molecular Pattern Molecules/chemistry , Respiratory Syncytial Viruses/immunology , Respiratory Syncytial Viruses/metabolism , Respiratory Syncytial Viruses/pathogenicity , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Viral Proteins/chemistry , Virus Diseases/virology , Viruses/metabolism , Viruses/pathogenicity
4.
Viruses ; 14(2)2022 02 18.
Article in English | MEDLINE | ID: covidwho-1707748

ABSTRACT

In the current context of the COVID-19 pandemic, it appears that our scientific resources and the medical community are not sufficiently developed to combat rapid viral spread all over the world. A number of viruses causing epidemics have already disseminated across the world in the last few years, such as the dengue or chinkungunya virus, the Ebola virus, and other coronavirus families such as Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV). The outbreaks of these infectious diseases have demonstrated the difficulty of treating an epidemic before the creation of vaccine. Different antiviral drugs already exist. However, several of them cause side effects or have lost their efficiency because of virus mutations. It is essential to develop new antiviral strategies, but ones that rely on more natural compounds to decrease the secondary effects. Polysaccharides, which have come to be known in recent years for their medicinal properties, including antiviral activities, are an excellent alternative. They are essential for the metabolism of plants, microorganisms, and animals, and are directly extractible. Polysaccharides have attracted more and more attention due to their therapeutic properties, low toxicity, and availability, and seem to be attractive candidates as antiviral drugs of tomorrow.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Polysaccharides/chemistry , Polysaccharides/pharmacology , Viruses/drug effects , Animals , Disease Outbreaks/prevention & control , Ebolavirus/drug effects , Humans , SARS-CoV-2/drug effects , Virus Diseases/drug therapy , Virus Replication/drug effects , Viruses/classification , Viruses/pathogenicity
5.
Viruses ; 14(2)2022 02 21.
Article in English | MEDLINE | ID: covidwho-1705332

ABSTRACT

Coinfection rates with other pathogens in coronavirus disease 2019 (COVID-19) varied during the pandemic. We assessed the latest prevalence of coinfection with viruses, bacteria, and fungi in COVID-19 patients for more than one year and its impact on mortality. A total of 436 samples were collected between August 2020 and October 2021. Multiplex real-time PCR, culture, and antimicrobial susceptibility testing were performed to detect pathogens. The coinfection rate of respiratory viruses in COVID-19 patients was 1.4%. Meanwhile, the rates of bacteria and fungi were 52.6% and 10.5% in hospitalized COVID-19 patients, respectively. Respiratory syncytial virus, rhinovirus, Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were the most commonly detected pathogens. Ninety percent of isolated A. baumannii was non-susceptible to carbapenem. Based on a multivariate analysis, coinfection (odds ratio [OR] = 6.095), older age (OR = 1.089), and elevated lactate dehydrogenase (OR = 1.006) were risk factors for mortality as a critical outcome. In particular, coinfection with bacteria (OR = 11.250), resistant pathogens (OR = 11.667), and infection with multiple pathogens (OR = 10.667) were significantly related to death. Screening and monitoring of coinfection in COVID-19 patients, especially for hospitalized patients during the pandemic, are beneficial for better management and survival.


Subject(s)
Bacterial Infections/epidemiology , COVID-19/epidemiology , Coinfection/microbiology , Coinfection/virology , Mycoses/epidemiology , Virus Diseases/epidemiology , Adolescent , Adult , Bacteria/classification , Bacteria/pathogenicity , COVID-19/microbiology , COVID-19/virology , Coinfection/epidemiology , Coinfection/mortality , Cross Infection/epidemiology , Cross Infection/microbiology , Cross Infection/virology , Female , Fungi/classification , Fungi/pathogenicity , Humans , Male , Middle Aged , Prevalence , Republic of Korea/epidemiology , Viruses/classification , Viruses/pathogenicity , Young Adult
8.
Viruses ; 14(1)2022 01 14.
Article in English | MEDLINE | ID: covidwho-1625756

ABSTRACT

Bats are reservoirs of a large number of viruses of global public health significance, including the ancestral virus for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the causative agent of coronavirus disease 2019 (COVID-19). Although bats are natural carriers of multiple pathogenic viruses, they rarely display signs of disease. Recent insights suggest that bats have a more balanced host defense and tolerance system to viral infections that may be linked to the evolutionary adaptation to powered flight. Therefore, a deeper understanding of bat immune system may provide intervention strategies to prevent zoonotic disease transmission and to identify new therapeutic targets. Similar to other eutherian mammals, bats have both innate and adaptive immune systems that have evolved to detect and respond to invading pathogens. Bridging these two systems are innate lymphocytes, which are highly abundant within circulation and barrier tissues. These cells share the characteristics of both innate and adaptive immune cells and are poised to mount rapid effector responses. They are ideally suited as the first line of defense against early stages of viral infections. Here, we will focus on the current knowledge of innate lymphocytes in bats, their function, and their potential role in host-pathogen interactions. Moreover, given that studies into bat immune systems are often hindered by a lack of bat-specific research tools, we will discuss strategies that may aid future research in bat immunity, including the potential use of organoid models to delineate the interplay between innate lymphocytes, bat viruses, and host tolerance.


Subject(s)
Chiroptera/immunology , Host-Pathogen Interactions/immunology , Immunity, Innate/immunology , Lymphocytes/immunology , Animals , Chiroptera/virology , Disease Reservoirs/virology , Humans , Immune Tolerance , Virus Diseases/immunology , Virus Diseases/transmission , Viruses/pathogenicity
9.
Front Immunol ; 12: 735866, 2021.
Article in English | MEDLINE | ID: covidwho-1590052

ABSTRACT

Bats are the only mammals with self-powered flight and account for 20% of all extant mammalian diversity. In addition, they harbor many emerging and reemerging viruses, including multiple coronaviruses, several of which are highly pathogenic in other mammals, but cause no disease in bats. How this symbiotic relationship between bats and viruses exists is not yet fully understood. Existing evidence supports a specific role for the innate immune system, in particular type I interferon (IFN) responses, a major component of antiviral immunity. Previous studies in bats have shown that components of the IFN pathway are constitutively activated at the transcriptional level. In this study, we tested the hypothesis that the type I IFN response in bats is also constitutively activated at the protein level. For this, we utilized highly sensitive Single Molecule (Simoa) digital ELISA assays, previously developed for humans that we adapted to bat samples. We prospectively sampled four non-native chiroptera species from French zoos. We identified a constitutive expression of IFNα protein in the circulation of healthy bats, and concentrations that are physiologically active in humans. Expression levels differed according to the species examined, but were not associated with age, sex, or health status suggesting constitutive IFNα protein expression independent of disease. These results confirm a unique IFN response in bat species that may explain their ability to coexist with multiple viruses in the absence of pathology. These results may help to manage potential zoonotic viral reservoirs and potentially identify new anti-viral strategies.


Subject(s)
Chiroptera/blood , Immunity, Innate , Interferon-alpha/blood , Viruses/immunology , Animals , Cell Line , Chiroptera/genetics , Chiroptera/immunology , Chiroptera/virology , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation , Host-Pathogen Interactions , Interferon-alpha/genetics , Species Specificity , Symbiosis , Transcription, Genetic , Viruses/pathogenicity
11.
J Pediatr ; 242: 18-24, 2022 03.
Article in English | MEDLINE | ID: covidwho-1587166

ABSTRACT

OBJECTIVE: To identify the etiologies of viral myocarditis in children in the pre-coronavirus disease 2019 era. STUDY DESIGN: This was a retrospective review of all patients (age <18 years) diagnosed with myocarditis and hospitalized at Rady Children's Hospital San Diego between 2000 and 2018. RESULTS: Twenty-nine patients met inclusion criteria. Of 28 (97%) patients who underwent testing for viruses, polymerase chain reaction was used in 24 of 28 (86% of cases), and 16 of 24 (67%) detected a virus. Pathogens were rhinovirus (6), influenza A/B (4), respiratory syncytial virus (RSV) (3), coronavirus (3), parvovirus B19 (2), adenovirus (2), and coxsackie B5 virus, enterovirus, and parainfluenza virus type 2 in one case each. Six (21%) patients had no pathogen detected but imaging and other laboratory test results were compatible with myocarditis. Age 0-2 years was associated with RSV, influenza A/B, coronavirus, and enteroviruses (P < .001). Twenty-one patients (72%) experienced full clinical recovery. Three patients (10%) required venoarterial extracorporeal membrane oxygenation (VA-ECMO), and all 3 recovered. Three others (10%) required and underwent successful cardiac transplantation without complications. Two patients (7%) died 9-10 days after hospitalization (1 had RSV and 1 had influenza A/B). Two other patients presented with complete atrioventricular block; 1 case (rhinovirus) resolved spontaneously, and 1 (coronavirus) resolved after support with VA-ECMO. Age <2 years, female sex, lower ejection fraction at admission, and greater initial and peak levels of brain natriuretic peptide were significant predictors of critical outcomes (use of VA-ECMO, listing for cardiac transplantation, and death). CONCLUSIONS: Viral nucleic acid-based testing revealed a wider spectrum of viruses that could be associated with myocarditis in children than previously reported and traditionally anticipated. A predilection of certain pathogens in the very young patients was observed. Whether the observed range of viral agents reflects an undercurrent of change in viral etiology or viral detection methods is unclear, but the wider spectrum of viral pathogens found underscores the usefulness of polymerase chain reaction testing to explore possible viral etiologies of myocarditis in children.


Subject(s)
Myocarditis/etiology , Myocarditis/virology , Virus Diseases/complications , Viruses/pathogenicity , Adolescent , California/epidemiology , Child , Child, Preschool , Female , Hospitals, Pediatric , Humans , Infant , Male , Myocarditis/diagnosis , Myocarditis/therapy , Polymerase Chain Reaction , Retrospective Studies
12.
Viruses ; 14(1)2021 12 24.
Article in English | MEDLINE | ID: covidwho-1580407

ABSTRACT

Only a mere fraction of the huge variety of human pathogenic viruses can be targeted by the currently available spectrum of antiviral drugs. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has highlighted the urgent need for molecules that can be deployed quickly to treat novel, developing or re-emerging viral infections. Sulfated polysaccharides are found on the surfaces of both the susceptible host cells and the majority of human viruses, and thus can play an important role during viral infection. Such polysaccharides widely occurring in natural sources, specifically those converted into sulfated varieties, have already proved to possess a high level and sometimes also broad-spectrum antiviral activity. This antiviral potency can be determined through multifold molecular pathways, which in many cases have low profiles of cytotoxicity. Consequently, several new polysaccharide-derived drugs are currently being investigated in clinical settings. We reviewed the present status of research on sulfated polysaccharide-based antiviral agents, their structural characteristics, structure-activity relationships, and the potential of clinical application. Furthermore, the molecular mechanisms of sulfated polysaccharides involved in viral infection or in antiviral activity, respectively, are discussed, together with a focus on the emerging methodology contributing to polysaccharide-based drug development.


Subject(s)
Antiviral Agents/pharmacology , Biological Products/pharmacology , COVID-19/epidemiology , Polysaccharides/pharmacology , Viruses/drug effects , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Biological Products/chemical synthesis , Biological Products/chemistry , COVID-19/drug therapy , Heparin/chemical synthesis , Heparin/chemistry , Heparin/pharmacology , Humans , Polysaccharides/chemistry , SARS-CoV-2/drug effects , Structure-Activity Relationship , Sulfates/chemistry , Sulfates/pharmacology , Virus Diseases/drug therapy , Virus Internalization/drug effects , Viruses/pathogenicity
13.
Viruses ; 13(12)2021 11 29.
Article in English | MEDLINE | ID: covidwho-1542801

ABSTRACT

Nestled within the Rocky Mountain National Forest, 114 scientists and students gathered at Colorado State University's Mountain Campus for this year's 21st annual Rocky Mountain National Virology Association meeting. This 3-day retreat consisted of 31 talks and 30 poster presentations discussing advances in research pertaining to viral and prion diseases. The keynote address provided a timely discussion on zoonotic coronaviruses, lessons learned, and the path forward towards predicting, preparing, and preventing future viral disease outbreaks. Other invited speakers discussed advances in SARS-CoV-2 surveillance, molecular interactions involved in flavivirus genome assembly, evaluation of ethnomedicines for their efficacy against infectious diseases, multi-omic analyses to define risk factors associated with long COVID, the role that interferon lambda plays in control of viral pathogenesis, cell-fusion-dependent pathogenesis of varicella zoster virus, and advances in the development of a vaccine platform against prion diseases. On behalf of the Rocky Mountain Virology Association, this report summarizes select presentations.


Subject(s)
Virology , Animals , Host-Pathogen Interactions , Humans , Pandemics/prevention & control , Prion Diseases/diagnosis , Prion Diseases/prevention & control , Prions/immunology , Prions/isolation & purification , Prions/pathogenicity , Vaccines , Virology/organization & administration , Virus Diseases/diagnosis , Virus Diseases/epidemiology , Virus Diseases/prevention & control , Virus Diseases/virology , Viruses/classification , Viruses/immunology , Viruses/isolation & purification , Viruses/pathogenicity
14.
PLoS Biol ; 19(4): e3001135, 2021 04.
Article in English | MEDLINE | ID: covidwho-1508487

ABSTRACT

Identifying the animal reservoirs from which zoonotic viruses will likely emerge is central to understanding the determinants of disease emergence. Accordingly, there has been an increase in studies attempting zoonotic "risk assessment." Herein, we demonstrate that the virological data on which these analyses are conducted are incomplete, biased, and rapidly changing with ongoing virus discovery. Together, these shortcomings suggest that attempts to assess zoonotic risk using available virological data are likely to be inaccurate and largely only identify those host taxa that have been studied most extensively. We suggest that virus surveillance at the human-animal interface may be more productive.


Subject(s)
Environmental Monitoring , Virus Diseases , Zoonoses/etiology , Zoonoses/prevention & control , Animals , Biodiversity , Disease Reservoirs/classification , Disease Reservoirs/statistics & numerical data , Environmental Monitoring/methods , Environmental Monitoring/standards , Host Specificity/genetics , Humans , Metagenomics/methods , Metagenomics/organization & administration , Metagenomics/standards , Phylogeny , Risk Assessment , Risk Factors , Selection Bias , Virus Diseases/epidemiology , Virus Diseases/etiology , Virus Diseases/prevention & control , Virus Diseases/transmission , Viruses/classification , Viruses/genetics , Viruses/isolation & purification , Viruses/pathogenicity , Zoonoses/epidemiology , Zoonoses/virology
15.
Sci Rep ; 11(1): 20058, 2021 10 08.
Article in English | MEDLINE | ID: covidwho-1459989

ABSTRACT

Respiratory viruses can be detected in 18.3 to 48.9% of critically ill adults with severe respiratory tract infections (RTIs). The present study aims to assess the clinical significance of respiratory viruses in pragmatically selected adults in medical intensive care unit patients and to identify factors associated with viral respiratory viral tract infections (VRTIs). We conducted a prospective study on critically ill adults with suspected RTIs without recognized respiratory pathogens. Viral cultures with monoclonal antibody identification, in-house real-time polymerase chain reaction (PCR) for influenza virus, and FilmArray respiratory panel were used to detect viral pathogens. Multivariable logistic regression was applied to identify factors associated with VRTIs. Sixty-four (40.5%) of the included 158 critically ill adults had respiratory viruses detected in their respiratory specimens. The commonly detected viruses included influenza virus (20), followed by human rhinovirus/enterovirus (11), respiratory syncitial virus (9), human metapneumovirus (9), human parainfluenza viruses (8), human adenovirus (7), and human coronaviruses (2). The FilmArray respiratory panel detected respiratory viruses in 54 (34.6%) patients, but showed negative results for seven of 13 patients with influenza A/H3 infection. In the multivariable logistic regression model, patient characters associated with VRTIs included those aged < 65 years, household contact with individuals with upper RTI, the presence of fever, cough with sputum production, and sore throat. Respiratory viruses were not uncommonly detected in the pragmatically selected adults with critical illness. The application of multiplex PCR testing for respiratory viruses in selected patient population is a practical strategy, and the viral detection rate could be further improved by the patient characters recognized in this study.


Subject(s)
Respiratory Tract Infections/epidemiology , Viruses/pathogenicity , Aged , Critical Illness , Female , Follow-Up Studies , Humans , Intensive Care Units , Male , Middle Aged , Prognosis , Prospective Studies , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/virology , Taiwan/epidemiology , Viruses/classification , Viruses/genetics , Viruses/isolation & purification
16.
Viruses ; 12(8)2020 08 18.
Article in English | MEDLINE | ID: covidwho-1453290

ABSTRACT

Enteric viral co-infections, infections involving more than one virus, have been reported for a diverse group of etiological agents, including rotavirus, norovirus, astrovirus, adenovirus, and enteroviruses. These pathogens are causative agents for acute gastroenteritis and diarrheal disease in immunocompetent and immunocompromised individuals of all ages globally. Despite virus-virus co-infection events in the intestine being increasingly detected, little is known about their impact on disease outcomes or human health. Here, we review what is currently known about the clinical prevalence of virus-virus co-infections and how co-infections may influence vaccine responses. While experimental investigations into enteric virus co-infections have been limited, we highlight in vivo and in vitro models with exciting potential to investigate viral co-infections. Many features of virus-virus co-infection mechanisms in the intestine remain unclear, and further research will be critical.


Subject(s)
Coinfection/virology , Gastroenteritis/virology , Virus Diseases/physiopathology , Viruses/classification , Viruses/pathogenicity , Animals , Asymptomatic Infections , Disease Models, Animal , Feces/virology , Humans , Intestines/virology , Mice , Primates
17.
Viruses ; 13(11)2021 10 27.
Article in English | MEDLINE | ID: covidwho-1488757

ABSTRACT

The current COVID-19 pandemic has highlighted the need for the research community to develop a better understanding of viruses, in particular their modes of infection and replicative lifecycles, to aid in the development of novel vaccines and much needed anti-viral therapeutics. Several viruses express proteins capable of forming pores in host cellular membranes, termed "Viroporins". They are a family of small hydrophobic proteins, with at least one amphipathic domain, which characteristically form oligomeric structures with central hydrophilic domains. Consequently, they can facilitate the transport of ions through the hydrophilic core. Viroporins localise to host membranes such as the endoplasmic reticulum and regulate ion homeostasis creating a favourable environment for viral infection. Viroporins also contribute to viral immune evasion via several mechanisms. Given that viroporins are often essential for virion assembly and egress, and as their structural features tend to be evolutionarily conserved, they are attractive targets for anti-viral therapeutics. This review discusses the current knowledge of several viroporins, namely Influenza A virus (IAV) M2, Human Immunodeficiency Virus (HIV)-1 Viral protein U (Vpu), Hepatitis C Virus (HCV) p7, Human Papillomavirus (HPV)-16 E5, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Open Reading Frame (ORF)3a and Polyomavirus agnoprotein. We highlight the intricate but broad immunomodulatory effects of these viroporins and discuss the current antiviral therapies that target them; continually highlighting the need for future investigations to focus on novel therapeutics in the treatment of existing and future emergent viruses.


Subject(s)
Immunomodulation , Ion Channels/metabolism , Viroporin Proteins/metabolism , Virus Diseases/drug therapy , Viruses/metabolism , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Autophagy , Host-Pathogen Interactions , Human Immunodeficiency Virus Proteins/chemistry , Human Immunodeficiency Virus Proteins/metabolism , Immune Evasion , Inflammasomes/immunology , Oncogene Proteins, Viral/chemistry , Oncogene Proteins, Viral/metabolism , Viral Matrix Proteins/chemistry , Viral Matrix Proteins/metabolism , Viral Proteins/chemistry , Viral Proteins/metabolism , Viral Regulatory and Accessory Proteins/chemistry , Viral Regulatory and Accessory Proteins/metabolism , Viral Structural Proteins/chemistry , Viral Structural Proteins/metabolism , Viroporin Proteins/chemistry , Virus Diseases/immunology , Virus Diseases/virology , Viruses/drug effects , Viruses/immunology , Viruses/pathogenicity
18.
Infect Dis Clin North Am ; 35(4): 1055-1075, 2021 12.
Article in English | MEDLINE | ID: covidwho-1487740

ABSTRACT

Health care-acquired viral respiratory infections are common and cause increased patient morbidity and mortality. Although the threat of viral respiratory infection has been underscored by the coronavirus disease 2019 (COVID-19) pandemic, respiratory viruses have a significant impact in health care settings even under normal circumstances. Studies report decreased nosocomial transmission when aggressive infection control measures are implemented, with more success noted when using a multicomponent approach. Influenza vaccination of health care personnel furthers decrease rates of transmission; thus, mandatory vaccination is becoming more common. This article discusses the epidemiology, transmission, and control of health care-associated respiratory viral infections.


Subject(s)
Cross Infection/prevention & control , Cross Infection/virology , Respiratory Tract Infections/prevention & control , Respiratory Tract Infections/virology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/transmission , Cross Infection/epidemiology , Cross Infection/transmission , Guideline Adherence , Health Personnel/standards , Humans , Infection Control/standards , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/transmission , SARS-CoV-2/pathogenicity , Vaccination , Viruses/classification , Viruses/pathogenicity
19.
Viruses ; 13(10)2021 10 04.
Article in English | MEDLINE | ID: covidwho-1481009

ABSTRACT

The livestock industry is constantly threatened by viral disease outbreaks, including infections with zoonotic potential. While preventive vaccination is frequently applied, disease control and eradication also depend on strict biosecurity measures. Clustered regularly interspaced palindromic repeats (CRISPR) and associated proteins (Cas) have been repurposed as genome editors to induce targeted double-strand breaks at almost any location in the genome. Thus, CRISPR/Cas genome editors can also be utilized to generate disease-resistant or resilient livestock, develop vaccines, and further understand virus-host interactions. Genes of interest in animals and viruses can be targeted to understand their functions during infection. Furthermore, transgenic animals expressing CRISPR/Cas can be generated to target the viral genome upon infection. Genetically modified livestock can thereby reduce disease outbreaks and decrease zoonotic threats.


Subject(s)
Gene Editing/methods , Livestock/virology , Viruses/genetics , Animal Husbandry/methods , Animals , CRISPR-Cas Systems/genetics , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , Genetic Engineering , Host Microbial Interactions/genetics , Virus Diseases/prevention & control , Viruses/pathogenicity
20.
Cells ; 10(11)2021 10 24.
Article in English | MEDLINE | ID: covidwho-1480600

ABSTRACT

Virus-related mortality and morbidity are due to cell/tissue damage caused by replicative pressure and resource exhaustion, e.g., HBV or HIV; exaggerated immune responses, e.g., SARS-CoV-2; and cancer, e.g., EBV or HPV. In this context, oncogenic and other types of viruses drive genetic and epigenetic changes that expand the tumorigenic program, including modifications to the ability of cancer cells to migrate. The best-characterized group of changes is collectively known as the epithelial-mesenchymal transition, or EMT. This is a complex phenomenon classically described using biochemistry, cell biology and genetics. However, these methods require enormous, often slow, efforts to identify and validate novel therapeutic targets. Systems biology can complement and accelerate discoveries in this field. One example of such an approach is Boolean networks, which make complex biological problems tractable by modeling data ("nodes") connected by logical operators. Here, we focus on virus-induced cellular plasticity and cell reprogramming in mammals, and how Boolean networks could provide novel insights into the ability of some viruses to trigger uncontrolled cell proliferation and EMT, two key hallmarks of cancer.


Subject(s)
Cell Plasticity/genetics , Gene Regulatory Networks , Virus Diseases/pathology , Viruses/pathogenicity , Animals , Cellular Reprogramming/genetics , Epithelial-Mesenchymal Transition/genetics , Humans , Neoplasms/genetics , Neoplasms/pathology , Systems Biology , Virus Diseases/genetics , Viruses/classification
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