• Here, using crystallography and cryo-electron microscopy, we determine the structures of FluPol A from human influenza A/NT/60/1968 (H3N2) and avian influenza A/duck/Fujian/01/2002 (H5N1) viruses at a resolution of 3.0-4.3 Å, in the presence or absence of a cRNA or vRNA template. (nature.com)
  • RNA viruses may escape acquired humoral and cellular immune responses by mutations in protective antigenic epitopes (e.g., avian influenza viruses), while accessory nonstructural proteins or multifunctional structural proteins interfere with the interferon system (e.g. (imperial.ac.uk)
  • R1a-B6-Fc fusions of both isotypes gave complete protection against lethal challenge with both pandemic A/California/07/2009 (H1N1)pdm09 and avian influenza A/Vietnam/1194/2004 (H5N1). (frontiersin.org)
  • We use a combination of cell-based and in vitro assays to show that the interface of the FluPol A dimer is required for vRNA synthesis during replication of the viral genome. (nature.com)
  • Our study provides high-resolution structures of medically relevant FluPol A , as well as insights into the replication mechanisms of the viral RNA genome. (nature.com)
  • It also exhaustively introduces the concrete mechanism of invading GC cells and the viral genome composition of adenovirus and herpes simplex virus type 1 (HSV-1). (frontiersin.org)
  • In order to solve this problem, we constructed an HIV-1 variant with a 300 bp long hairpin structure in the 3' part of the genome corresponding to the Nef gene (HIV-lhNef). (biomedcentral.com)
  • Further, the 'viral genome' was derived in silico, which means no actual virus was physically lysed & analyzed, let alone proven to exist. (linode.com)
  • RNA wasn't physically extracted by whole lysed virions, but instead, as the authors state: 'We extracted RNA for whole genome sequencing of the viral isolate. (linode.com)
  • All sequencing was performed by a process called 'alignment' - where complex computational algorithms are used to reconstruct a large sequence in silico that closely resembles a pre-selected genome from a soup of millions of short gene fragments of unknown origin. (linode.com)
  • They always use a 'culture', use a specific cell line, apply the same chemical assault to the culture in order to induce a CPE, take an EM photo of the culture soup with no isolation of particles, and then apply a non-purified sample of this soup to a computer-based program that reconstructs a fictitious genome. (linode.com)
  • Virologists are trained and told to follow a specific procedure in 'isolating' & 'sequencing' viruses because both the virus & the viral genome don't exist in nature. (linode.com)
  • The viral genome is always generated in silico through the computational reconstruction of a larger gene out of millions of short gene fragments of unknown origins. (linode.com)
  • In participating UK research institutions, investigators can publish open access in Genome Research, Genes & Development, RNA, and Learning & Memory without article publication charges and all staff can read the entire renowned Cold Spring Harbor journal collection. (cshlpress.com)
  • After the initial or primary infection, some infected people experience sporadic episodes of viral reactivation or outbreaks. (wikipedia.org)
  • Asymptomatic reactivation means that the virus causes atypical, subtle, or hard-to-notice symptoms that are not identified as an active herpes infection, so acquiring the virus is possible even if no active HSV blisters or sores are present. (wikipedia.org)
  • A daily swab of the genital area was self-collected for HSV-2 detection by polymerase chain reaction, to compare the effect of valaciclovir versus placebo on asymptomatic viral shedding in immunocompetent, HSV-2 seropositive subjects without a history of symptomatic genital herpes infection. (wikipedia.org)
  • Several clinical observations point to an intricate crosstalk between iron (Fe) metabolism and chronic hepatitis C virus (HCV) infection. (microbiologyresearch.org)
  • In order to better understand differences in the outcome of infectious bursal disease virus (IBDV) infection, we inoculated a very virulent (vv) strain into White Leghorn chickens of inbred line W that was previously reported to experience over 24% flock mortality, and three inbred lines (15I, C.B4 and 0) that were previously reported to display no mortality. (imperial.ac.uk)
  • Our findings demonstrate AAV delivery of cross-subtype neutralizing nanobodies may be an effective strategy to prevent influenza infection and provide long-term protection independent of a host induced immune response. (frontiersin.org)
  • 2012). This is due to the establishment, early after primary infection, of a viral reservoir that is responsible for the persistence of low levels of plasma viremia in patients under suppressive ART (Chun et al. (europa.eu)
  • Vaccine-induced antibody and T cell responses correlated with protection against lethal influenza virus infection. (researchsquare.com)
  • Moreover, antibody responses induced by influenza virus vaccines are usually short-lived and less cross-reactive against antigenically drifted virus variants than those induced by a natural influenza virus infection 1 . (researchsquare.com)
  • Additionally, vaccine-induced neutralizing antibody titers diminish over time, thereby affecting the extent of protection against infection during an entire influenza season and the subsequent seasons. (researchsquare.com)
  • Many viruses, including Kaposi Sarcoma Herpesvirus (KSHV), have evolved sophisticated countermeasures to extend the life of an infected host cell to support establishment of infection and virus proliferation. (mdpi.com)
  • We also show that in addition to Bid and Puma, KsBcl-2 is able to engage with a broad range of other host cell death inducers, thus making it a potent enabler of viral infection and proliferation. (mdpi.com)
  • In an outbreak, the virus in a nerve cell becomes active and is transported via the neuron's axon to the skin, where virus replication and shedding occur and may cause new sores. (wikipedia.org)
  • We also show that a nanobody (a single-domain antibody) that interferes with FluPol A dimerization inhibits the synthesis of vRNA and, consequently, inhibits virus replication in infected cells. (nature.com)
  • Fig. 4: Nb8205, which binds FluPol A at the dimer interface, inhibits cRNA to vRNA replication and virus growth. (nature.com)
  • HIV persistence may arise from ongoing residual virus replication and/or from latently-infected cells defined as the cellular reservoir in which long-lived resting memory CD4+ T cells harbouring an integrated but transcriptionally silent provirus represent the largest pool in the blood (Chomont et al. (europa.eu)
  • However, HIV-lhNef demonstrated a severe production and replication defect, which we were able to solve by selecting spontaneous virus variants with truncated hairpin structures. (biomedcentral.com)
  • This process is regulated by both viral and cellular factors, which are necessary for an efficient viral replication as well as for the setting up of viral latency, leading to a repressed transcription of the integrated provirus.nnRESULTS: In this study, we examined the role of two parameters in HIV-1 LTR promoter activity. (cnrs.fr)
  • We have previously described R1a-B6, an alpaca-derived single domain antibody (nanobody), that is capable of potent cross-subtype neutralization in vitro of H1N1, H5N1, H2N2, and H9N2 influenza viruses, through binding to a highly conserved epitope in the influenza hemagglutinin stem region. (frontiersin.org)
  • A more practical and cost-effective strategy would be to use antibody gene therapy which would provide long term sustainable protection through antibody production within the patient. (frontiersin.org)
  • Protective anti-influenza immunity often correlates with antibody responses to influenza surface glycoproteins, particularly hemagglutinin (HA), the main antigenic determinant on the surface of both influenza virus and infected cells. (researchsquare.com)
  • However, due to antigenic drift in influenza viruses, vaccines need to be updated every year to protect against the circulating strains of the virus. (researchsquare.com)
  • This may have implications for the development of virus strains to be used as live-attenuated virus vaccines. (biomedcentral.com)
  • A much more promising strategy is to use recombinant monoclonal antibodies (mAbs) against influenza and several are currently in clinical development ( 9 - 13 ). (frontiersin.org)
  • LXGG sequence is recognized by viral and cellular deubiquitinating enzymes. (microbiologyresearch.org)
  • Lastly, we noticed an enrichment of predicted G4 sequences in the promoter of TOP1-repressed cellular genes.nnCONCLUSIONS: Our results demonstrate the formation of a TOP1/G4 complex on the HIV-1 LTR promoter and its repressive effect on the promoter activity. (cnrs.fr)
  • It was declared this constitutes evidence of a new viral pathogen '2019-nCoV', later to be renamed SARS-CoV-2. (linode.com)
  • This harmless commensal organism can acquire a mixture of comprehensive mobile genetic elements that contain genes encoding viru-lence factors, becoming an emerging human pathogen capable of causing a broad spectrum of intestinal and extraintestinal diseases. (preprints.org)
  • Introduction: OAS1(2'-5'-oligoadenylate synthetase 1) is a member of the Interferon-Stimulated Genes which plays an important role in the antiviral process. (bvsalud.org)
  • We showed previously that cytoplasmic release of mtDNA activates the cGAS STING TBK1 pathway resulting in interferon-stimulated gene (ISG) expression that promotes antiviral immunity4. (regenerativemedicine.net)
  • Here, we find that persistent mtDNA stress is not associated with basally activated NF-κB signalling or interferon gene expression typical of an acute antiviral response. (regenerativemedicine.net)
  • DNA viruses such as herpesvirus and poxvirus have multiple genes, some of them host-derived, which interfere with effective innate or acquired immune responses. (imperial.ac.uk)
  • We identified DNA topoisomerase1 (TOP1) to be a potent repressor of this promoter and linked this repression to its catalytic domain. (cnrs.fr)
  • Deletion of the A56R gene results in varying effects on vaccinia virus virulence. (microbiologyresearch.org)
  • This review summarizes new de-velopments in our understanding of diverse virulence factors associated encoding genes used by different pathotypes of enteric pathogenic E. coli to cause intestinal and extraintestinal diseases in humans. (preprints.org)
  • Hepatitis E virus (HEV) ORF1 protein (pORF1) contains methyltransferase (MetT), papain-like cysteine protease (PCP), RNA helicase (Hel) and RNA-dependent RNA polymerase (RdRp) domains. (microbiologyresearch.org)
  • Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomic names Human alphaherpesvirus 1 and Human alphaherpesvirus 2, are two members of the human Herpesviridae family, a set of viruses that produce viral infections in the majority of humans. (wikipedia.org)
  • Despite several vaccine candidates available on the market, influenza virus is responsible for severe illness in humans, with a substantial global death toll every year (https://gis.cdc.gov/grasp/fluview/flu_by_age_virus.html). (researchsquare.com)
  • As neurotropic and neuroinvasive viruses, HSV-1 and -2 persist in the body by hiding from the immune system in the cell bodies of neurons, particularly in sensory ganglia. (wikipedia.org)
  • Immunoevasion is a common ploy by which viruses neutralize or evade immune responses. (imperial.ac.uk)
  • The persistence of HIV in treated patients results from the establishment of a viral reservoir insensitive to ART and poorly visible to the immune system. (europa.eu)
  • Therefore, there is an urgent need for a better cost-effective influenza vaccine which can induce antigenically broader and long-lasting immune response. (researchsquare.com)
  • Additionally, we confirmed the folding of a Guanine quadruplex (G4) structure in the HIV-1 promoter and its repressive effect. (cnrs.fr)
  • Immunosuppression can be caused by pathogens such as chicken infectious anemia virus, infectious bursal disease virus, reovirus, and some retroviruses (e.g., reticuloendotheliosis virus). (imperial.ac.uk)
  • So, this review highlights the various types of NPs used in the techniques that have worked in the new paradigm in viral vaccinology for infectious diseases. (researchgate.net)
  • Although antiviral drugs such as Oseltamivir are available to control the spread of the virus their effectiveness is limited in treating patients with influenza ( 5 , 6 ). (frontiersin.org)
  • The use of siRNA and shRNA as antiviral therapeutic is limited because of the emergence of viral escape mutants. (biomedcentral.com)
  • In addition, since the gene encoding the A56 protein is non-essential, it can be used as an insertion point for foreign genes and has been deleted in some viruses that are in clinical development as oncolytic agents. (microbiologyresearch.org)
  • This review integrates most experimental studies and clinical trials of various oncolytic viruses (OVs) in the diagnosis and treatment of GC. (frontiersin.org)
  • Inherited risk for stroke is likely multigenic, although specific single-gene disorders with stroke as a component of the phenotype demonstrate the potency of genetics in determining stroke risk. (medscape.com)
  • All the other papers presented (if you care to check them) likewise exclude proper controls, fail to demonstrate the physical isolation of actual viruses, and do not physically sequence said viruses. (linode.com)
  • There are numerous peer reviewed research papers that demonstrate how the virus has been isolated. (linode.com)
  • In a pandemic, a new influenza virus emerges and infects the human population which has little or no pre-existing immunity ( 2 , 3 ). (frontiersin.org)
  • Human immunodeficiency virus type 1 (HIV-1) can be inhibited by means of RNA silencing or interference (RNAi) using synthetic short interfering RNAs (siRNAs) or gene constructs encoding short hairpin RNAs (shRNAs) or long hairpin RNAs (lhRNAs). (biomedcentral.com)
  • They reveal the existence of a new mechanism of TOP1/G4-dependent transcriptional repression conserved between viral and human genes. (cnrs.fr)
  • This mechanism contrasts with the known property of TOP1 as global transcriptional activator and offers new perspectives for anti-cancer and anti-viral strategies. (cnrs.fr)
  • Influenza vaccine effectiveness could be improved by combination with an adjuvant with the potential to enhance the host-vaccine response both quantitatively and qualitatively. (researchsquare.com)
  • Metazoans often trigger premature cell death in response to infections by larger DNA viruses as part of an immediate response to counter the viral threat. (mdpi.com)
  • The goal of this study was to explore a RIG-I agonist (SDI-nanogel) and a TLR7/8 agonist (Imidazoquinoline (IMDQ)‐PEG‐Chol) as adjuvants, when co-administered with a licensed quadrivalent inactivated influenza vaccine (QIV), and to determine the role of these adjuvants in directing helper T (Th) cell responses for their role in the immunoglobulin (Ig) class switching. (researchsquare.com)
  • We also provide evidence that virion-associated cholesterol contributes to the interaction between HCV particles and apolipoprotein E. The molecular basis for the effects of different sterols on HCV infectivity is discussed. (microbiologyresearch.org)
  • Processes orchestrated or driven by a plethora of genes, plant hormones, and inherent biological timing mechanisms facilitated by secondary molecules, which result in the systematic transformation of plants and plant parts, from one stage of maturity to another. (lookformedical.com)
  • To evaluate the potential of R1a-B6 for immunoprophylaxis, we have reformatted it as an Fc fusion for adeno-associated viral (AAV) vector delivery. (frontiersin.org)
  • The chimeric virus can also have a reduced transduction capability with respect to one or more cells or tissues (e.g., liver), which can be desirable in terms of targeting the vector to the target tissue of interest and reducing dosage of vector to be administered. (justia.com)
  • Although these escape variants lost the ability to trans-inhibit HIV-1, they effectively outgrew the wild-type virus in competition experiments in SupT1 cells. (biomedcentral.com)
  • Cross-subtype neutralizing single domain antibodies against influenza present new opportunities for immunoprophylaxis and pandemic preparedness. (frontiersin.org)
  • Further, in particular embodiments, the chimeric virus has a different immunological profile than one or both of the parent viruses (i.e., is only weakly or not at all recognized by neutralizing antisera or antibodies against the parent virus), thereby allowing for administration to subjects that have antibodies directed against the parent virus or repeat administration following administration of another serotype. (justia.com)
  • Within each experimental group, some individuals experienced more severe disease than others but line 15I birds experienced milder disease based on average clinical scores, percentage of birds with gross pathology, average bursal lesion scores and average peak bursal virus titre. (imperial.ac.uk)
  • Influenza virus continues to be a major public health concern, causing both annual epidemics and occasional pandemics ( 1 ). (frontiersin.org)
  • In particular embodiments, the chimeric viruses of the invention have enhanced transduction capability (e.g., transduction of skeletal muscle, cardiac muscle, glial cells, astrocytes, liver, retina and/or lung, etc.), enhanced levels of transgene expression and/or earlier onset of transgene expression. (justia.com)
  • However, gene constructs encoding lhRNA molecules face problems with delivery to the right cells in an infected individual. (biomedcentral.com)
  • COLD SPRING HARBOR, NEW YORK -- In an important, comprehensive, and timely review, an expert team from the University of California Berkeley details the methodologies used in nucleic acid-based tests for detecting the presence of SARS-CoV-2, the virus that causes COVID-19. (cshlpress.com)
  • 0.01) and, when stimulated ex vivo with LPS, showed more rapid up-regulation of pro-inflammatory gene expression than those from line 15I birds. (imperial.ac.uk)
  • For example, as compared with AAV2, AAV1 can be administered at lower dosages (i.e., fewer particles) and can express the transgene at earlier time points and at higher levels of expression. (justia.com)
  • Low shear stress up-regulates expression of vascular cell adhesion molecule 1 (VCAM-1), while increased shear stress can lead to increased gene expression of intercellular adhesion molecule 1 (ICAM-1). (medscape.com)
  • Fig. 3: Structures of H3N2 FluPol A bound to cRNA promoter. (nature.com)
  • Our earlier study has demonstrated that hepatitis C virus (HCV)-associated cholesterol plays a key role in virus infectivity. (microbiologyresearch.org)
  • The actual researchers with actual credentials to actually study the SARS-C0V-2 virus properly know how to isolate the virus. (linode.com)
  • The present invention provides chimeric virus vectors that have been designed to exhibit one or more properties of interest (e.g., enhanced tissue tropism). (justia.com)
  • Their simple modular structure and single open reading frame format are highly amenable to gene therapy-mediated delivery. (frontiersin.org)
  • It is becoming clear that vectors based upon adeno-associated virus (AAV) are the vectors of choice for certain gene therapy applications such as muscle delivery. (justia.com)