16,666 results match your criteria Vaccinia

The Life Cycle of the Vaccinia Virus Genome.

Annu Rev Virol 2022 May 18. Epub 2022 May 18.

Department of Biochemistry and Molecular Biology, The Medical University of South Carolina, Charleston, South Carolina, USA; email:

Poxviruses, of which vaccinia virus is the prototype, are a large family of double-stranded DNA viruses that replicate exclusively in the cytoplasm of infected cells. This physical and genetic autonomy from the host cell nucleus necessitates that these viruses encode most, if not all, of the proteins required for replication in the cytoplasm. In this review, we follow the life of the viral genome through space and time to address some of the unique challenges that arise from replicating a 195-kb DNA genome in the cytoplasm. Read More

View Article and Full-Text PDF

Disruption of the cGAS/STING axis does not impair sensing of MVA in BHK21 cells.

J Gen Virol 2022 May;103(5)

Department of Microbial Sciences, University of Surrey, Guildford, UK.

Modified vaccinia Ankara (MVA) is an attenuated strain of vaccinia virus (VACV), a dsDNA virus that replicates its genome in the cytoplasm and as a result is canonically sensed by the cyclic GMP-AMP synthase (cGAS) and its downstream stimulator of interferon genes (STING). MVA has a highly restricted host range due to major deletions in its genome including inactivation of immunomodulatory genes, only being able to grow in avian cells and the hamster cell line BHK21. Here we studied the interplay between MVA and the cGAS/STING DNA in this permissive cell line and determined whether manipulation of this axis could impact MVA replication and cell responses. Read More

View Article and Full-Text PDF

Vaccinia Virus Attenuation by Codon Deoptimization of the A24R Gene for Vaccine Development.

Microbiol Spectr 2022 May 18:e0027222. Epub 2022 May 18.

Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.

Poxviruses have large DNA genomes, and they are able to infect multiple vertebrate and invertebrate animals, including humans. Despite the eradication of smallpox, poxvirus infections still remain a significant public health concern. Vaccinia virus (VV) is the prototypic member in the family and it has been used extensively for different prophylactic applications, including the generation of vaccines against multiple infectious diseases and/or for oncolytic treatment. Read More

View Article and Full-Text PDF

Cytoplasmic gene expression: lessons from poxviruses.

Trends Biochem Sci 2022 May 15. Epub 2022 May 15.

Department of Biochemistry and Cancer Therapy Research Center (CTRC), Theodor Boveri-Institute, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, Germany; Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), 97080 Wuerzburg, Germany. Electronic address:

In eukaryotic cells, the process of gene expression is confined to the nucleus and enabled by multisubunit RNA polymerases (RNAPs). Many viruses make use of the host cellular gene expression apparatus during infection, and hence transfer their genome at least transiently to the host nucleus. However, poxviruses have evolved a different strategy to propagate. Read More

View Article and Full-Text PDF

Fluorescence-Based Activity Screening Assay Reveals Small Molecule Inhibitors of Vaccinia Virus mRNA Decapping Enzyme D9.

ACS Chem Biol 2022 May 16. Epub 2022 May 16.

Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Pasteura 5, Warsaw 02-093, Poland.

Vaccinia virus (VACV) represents a family of poxviruses, which possess their own decapping machinery as a part of their strategy to eliminate host mRNAs and evade the innate immune response. D9 is one of the two encoded VACV decapping enzymes that is responsible for cap removal from the 5' end of both host mRNA transcripts and viral double-stranded RNAs. Little is known about the structural requirements for D9 inhibition by small molecules. Read More

View Article and Full-Text PDF

Seroprevalence, associated risk factors and clinico-pathological studies of buffalopox disease in various regions of Punjab province, Pakistan.

Pol J Vet Sci 2022 Mar;25(1):137-147

Institute of Microbiology, Faculty of Veterinary Science, University of Agriculture, Faisalabad, Pakistan, 38000.

Buffalopox (BPX) is a highly contagious disease that causes high morbidity and production losses in buffaloes. During this study, seroprevalence, effect of various associated risk factors, and pathological studies of BPX were recorded in the Punjab province. A total of 97 blood samples and 63 scabs were collected from clinically pox suspected buffaloes. Read More

View Article and Full-Text PDF

Early Post-Vaccination Gene Signatures Correlate With the Magnitude and Function of Vaccine-Induced HIV Envelope-Specific Plasma Antibodies in Infant Rhesus Macaques.

Front Immunol 2022 27;13:840976. Epub 2022 Apr 27.

Department of Microbiology and Immunology, Center for AIDS Research, and Children's Research Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.

A better understanding of the impact of early innate immune responses after vaccine priming on vaccine-elicited adaptive immune responses could inform rational design for effective HIV vaccines. The current study compared the whole blood molecular immune signatures of a 3M-052-SE adjuvanted HIV Env protein vaccine to a regimen combining the adjuvanted Env protein with simultaneous administration of a modified Vaccinia Ankara vector expressing HIV Env in infant rhesus macaques at days 0, 1, and 3 post vaccine prime. Both vaccines induced a rapid innate response, evident by elevated inflammatory plasma cytokines and altered gene expression. Read More

View Article and Full-Text PDF

Intravenous Oncolytic Vaccinia Virus Therapy Results in a Differential Immune Response between Cancer Patients.

Cancers (Basel) 2022 Apr 27;14(9). Epub 2022 Apr 27.

Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds LS9 7TF, UK.

is an engineered Wyeth-strain vaccinia oncolytic virus (OV), which has been tested extensively in clinical trials, demonstrating enhanced cytotoxic T cell infiltration into tumours following treatment. Favourable immune consequences to include the induction of an interferon (IFN) response, followed by inflammatory cytokine/chemokine secretion. This promotes tumour immune infiltration, innate and adaptive immune cell activation and T cell priming, culminating in targeted tumour cell killing, i. Read More

View Article and Full-Text PDF

VRK1 Predicts Poor Prognosis and Promotes Bladder Cancer Growth and Metastasis and .

Front Pharmacol 2022 26;13:874235. Epub 2022 Apr 26.

Department of Oncology Radiotherapy, Yancheng No. 1 People's Hospital, Yancheng, China.

Bladder cancer (BC) is one of the most common malignant tumors in the urinary system with growing morbidity and diagnostic rate in recent years. Therefore, identifying new molecular biomarkers that inhibit the progression of bladder cancer is needed for developing further therapeutics. This study found a new potential treatment target: vaccinia-related kinase 1 (VRK1) and explored the function and mechanism of VRK1 in the development of bladder cancer. Read More

View Article and Full-Text PDF

Dysregulation of Cellular VRK1, BAF, and Innate Immune Signaling by the Vaccinia Virus B12 Pseudokinase.

J Virol 2022 May 11:e0039822. Epub 2022 May 11.

Nebraska Center for Virology, University of Nebraska, Lincoln, Nebraska, USA.

Poxvirus proteins remodel signaling throughout the cell by targeting host enzymes for inhibition and redirection. Recently, it was discovered that early in infection the vaccinia virus (VACV) B12 pseudokinase copurifies with the cellular kinase VRK1, a proviral factor, in the nucleus. Although the formation of this complex correlates with inhibition of cytoplasmic VACV DNA replication and likely has other downstream signaling consequences, the molecular mechanisms involved are poorly understood. Read More

View Article and Full-Text PDF

One enzyme, many substrates: How the vaccinia virus enzyme D9 decaps host and viral mRNAs alike.

Structure 2022 May;30(5):653-654

Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 6, D-14195 Berlin, Germany. Electronic address:

The decapping enzyme D9 acts on host mRNA and viral double-stranded RNA to promote viral replication in host cells. In this issue of Structure, Peters et al. (2022) present crystal structures of mGDP-bound D9 to highlight how a conventional fold is adapted to target a wide variety of RNA substrates. Read More

View Article and Full-Text PDF

Purification, characterization and functional site prediction of the vaccinia-related kinase 2A small transmembrane domain.

MethodsX 2022 16;9:101704. Epub 2022 Apr 16.

Integrated Biophysics and Structural Biology Lab, ACTREC, Tata Memorial Centre, Tata Memorial Centre, Sector 22, Kharghar, Navi Mumbai 410210, India.

Vaccinia-related kinases (VRK) are serine-threonine kinases that regulate several signaling pathways. The isoform-VRK2A of one such kinase VRK2 controls cell stress response by interacting with TAK1, a mitogen-activated protein 3 kinase (MAP3K), via its partly cytosolic C-terminal transmembrane domain (VTMD). To establish the driving force and identify the key residues of the VRK2A-TAK1 interaction, we expressed and purified the standalone 3. Read More

View Article and Full-Text PDF

Trafficking and retention of protein antigens across systems and immune cell types.

Cell Mol Life Sci 2022 May 3;79(5):275. Epub 2022 May 3.

Department of Medicine, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, USA.

In response to infection or vaccination, the immune system initially responds non-specifically to the foreign insult (innate) and then develops a specific response to the foreign antigen (adaptive). The programming of the immune response is shaped by the dispersal and delivery of antigens. The antigen size, innate immune activation and location of the insult all determine how antigens are handled. Read More

View Article and Full-Text PDF

Four Decades of Prophylactic EBV Vaccine Research: A Systematic Review and Historical Perspective.

Front Immunol 2022 14;13:867918. Epub 2022 Apr 14.

Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA, United States.

Background: Epstein-Barr virus (EBV) is the causal agent of infectious mononucleosis and has been associated with various cancers and autoimmune diseases. Despite decades of research efforts to combat this major global health burden, there is no approved prophylactic vaccine against EBV. To facilitate the rational design and assessment of an effective vaccine, we systematically reviewed pre-clinical and clinical prophylactic EBV vaccine studies to determine the antigens, delivery platforms, and animal models used in these studies. Read More

View Article and Full-Text PDF

Peptides-Coated Oncolytic Vaccines for Cancer Personalized Medicine.

Front Immunol 2022 14;13:826164. Epub 2022 Apr 14.

Drug Research Program (DRP) ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.

Oncolytic Viruses (OVs) work through two main mechanisms of action: the direct lysis of the virus-infected cancer cells and the release of tumor antigens as a result of the viral burst. In this sc.enario, the OVs act as cancer vaccines, since the immunogenicity of the virus is combined with tumor antigens, that direct the specificity of the anti-tumor adaptive immune response. Read More

View Article and Full-Text PDF

Efficacy of Liming Forest Soil in the Context of African Swine Fever Virus.

Viruses 2022 Mar 31;14(4). Epub 2022 Mar 31.

Institute of Animal Hygiene and Veterinary Public Health, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 1, 04103 Leipzig, Germany.

Since September 2020, Germany has experienced the first ever outbreak of African swine fever (ASF). The first known cases occurred exclusively in wild boar in forest areas in Brandenburg and Saxony; in July 2021, infected domestic pigs were also confirmed for the first time. As wild boar are considered the main reservoir for the virus in the European region, an effective interruption of this infection chain is essential. Read More

View Article and Full-Text PDF

Conditions That Simulate the Environment of Atopic Dermatitis Enhance Susceptibility of Human Keratinocytes to Vaccinia Virus.

Cells 2022 Apr 14;11(8). Epub 2022 Apr 14.

Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA.

Individuals with underlying chronic skin conditions, notably atopic dermatitis (AD), are disproportionately affected by infections from members of the herpesviridae, papovaviridae, and poxviridae families. Many patients with AD experience recurrent, widespread cutaneous viral infections that can lead to viremia, serious organ complications, and even death. Little is known about how the type 2 inflammatory environment observed in the skin of AD patients impacts the susceptibility of epidermal cells (keratinocytes) to viral pathogens. Read More

View Article and Full-Text PDF

Low-Temperature Multiple Micro-Dispensing on Microneedles for Accurate Transcutaneous Smallpox Vaccination.

Vaccines (Basel) 2022 Apr 4;10(4). Epub 2022 Apr 4.

Department of Biomaterials Science (BK21 Four Program), Life and Industry Convergence Institute, Pusan National University, Miryang 50463, Korea.

Smallpox is an acute contagious disease caused by the variola virus. According to WHO guidelines, the smallpox vaccine is administrated by scarification into the epidermis using a bifurcated needle moistened with a vaccine solution. However, this invasive vaccination method involving multiple skin punctures requires a special technique to inoculate, as well as a cold chain for storage and distribution of vaccine solutions containing a live virus. Read More

View Article and Full-Text PDF

Development of a Universal Epitope-Based Influenza Vaccine and Evaluation of Its Effectiveness in Mice.

Vaccines (Basel) 2022 Mar 29;10(4). Epub 2022 Mar 29.

Center for Strategic Planning and Management of Medical and Biological Health Risks, Federal State Budgetary Institution, Federal Medical-Biological Agency, 119833 Moscow, Russia.

Vaccination is an effective and economically viable means of protection against the influenza virus, but due to rapid viral evolution, modern seasonal vaccines are not effective enough. Next-generation vaccines are designed to provide protection against a wide range of influenza virus strains, including pandemic variants. In our work, we made an epitope-based universal vaccine, rMVA-k1-k2, against the influenza virus based on the modified vaccinia Ankara (MVA) vector and using our own algorithms to select epitopes from conserved fragments of the NP, M1 and HA proteins of influenza A and B. Read More

View Article and Full-Text PDF

Protective CD8+ T Cell Response Induced by Modified Vaccinia Virus Ankara Delivering Ebola Virus Nucleoprotein.

Vaccines (Basel) 2022 Mar 29;10(4). Epub 2022 Mar 29.

German Center for Infection Research, Partner Site Munich, 80539 Munich, Germany.

The urgent need for vaccines against Ebola virus (EBOV) was underscored by the large outbreak in West Africa (2014-2016). Since then, several promising vaccine candidates have been tested in pre-clinical and clinical studies. As a result, two vaccines were approved for human use in 2019/2020, of which one includes a heterologous adenovirus/Modified Vaccinia virus Ankara (MVA) prime-boost regimen. Read More

View Article and Full-Text PDF

Oncolytic Vaccinia Virus Augments T Cell Factor 1-Positive Stem-like CD8 T Cells, Which Underlies the Efficacy of Anti-PD-1 Combination Immunotherapy.

Biomedicines 2022 Mar 30;10(4). Epub 2022 Mar 30.

Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.

Oncolytic virotherapy has garnered attention as an antigen-agnostic therapeutic cancer vaccine that induces cancer-specific T cell responses without additional antigen loading. As anticancer immune responses are compromised by a lack of antigenicity and chronic immunosuppressive microenvironments, an effective immuno-oncology modality that converts cold tumors into hot tumors is crucial. To evaluate the immune-activating characteristics of oncolytic vaccinia virus (VACV; JX-594, pexastimogene devacirepvec), diverse murine syngeneic cancer models with different tissue types and immune microenvironments were used. Read More

View Article and Full-Text PDF

Smallpox vaccination induces a substantial increase in commensal skin bacteria that promote pathology and influence the host response.

PLoS Pathog 2022 04 21;18(4):e1009854. Epub 2022 Apr 21.

Department of Pathology, University of Cambridge, Cambridge, United Kingdom.

Interactions between pathogens, host microbiota and the immune system influence many physiological and pathological processes. In the 20th century, widespread dermal vaccination with vaccinia virus (VACV) led to the eradication of smallpox but how VACV interacts with the microbiota and whether this influences the efficacy of vaccination are largely unknown. Here we report that intradermal vaccination with VACV induces a large increase in the number of commensal bacteria in infected tissue, which enhance recruitment of inflammatory cells, promote tissue damage and influence the host response. Read More

View Article and Full-Text PDF

The Multiplicity of Infection of Recombinant Vaccinia Virus Expressing the T7 RNA Polymerase Determines the Rescue Efficiency of Vesicular Stomatitis Virus.

Front Microbiol 2022 4;13:846426. Epub 2022 Apr 4.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Public Health of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.

Vesicular stomatitis virus (VSV) has a wide range of cell tropism, making it a prototype of studying the negative-strand RNA virus (NSRV), including virus-host interactions and vaccine development. Although VSV rescue systems have been progressively optimized throughout time, the T7-based expression system is the most commonly utilized to rescue VSV. However, it remains a significant barrier for many labs. Read More

View Article and Full-Text PDF

Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anti-Cancer Immunity in Patients.

Cancer Immunol Res 2022 Apr 19. Epub 2022 Apr 19.

St James's Institute of Oncology, Leeds, West Yorkshire, United Kingdom.

Improving the chances of curing cancer patients who have had surgery to remove metastatic sites of disease is a priority area for cancer research. Pexa-Vec (Pexastimogene Devacirepvec; JX-594, TG6006) is a principally immunotherapeutic oncolytic virus that has reached late-phase clinical trials. We report the results of a single-center, non-randomized biological endpoint study (trial registration: EudraCT number 2012-000704-15), which builds on the success of the pre-surgical intravenous (i. Read More

View Article and Full-Text PDF

A Poxvirus Decapping Enzyme Colocalizes with Mitochondria To Regulate RNA Metabolism and Translation and Promote Viral Replication.

mBio 2022 Apr 18:e0030022. Epub 2022 Apr 18.

Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USA.

Decapping enzymes remove the 5' cap of eukaryotic mRNA, leading to accelerated RNA decay. They are critical in regulating RNA homeostasis and play essential roles in many cellular and life processes. They are encoded in many organisms and viruses, including vaccinia virus, which was used as the vaccine to eradicate smallpox. Read More

View Article and Full-Text PDF

Rapid and quantitative evaluation of vaccinia virus-induced host shutoff using newly generated cell lines stably expressing secreted Gaussia luciferase.

J Med Virol 2022 Apr 12. Epub 2022 Apr 12.

Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USA.

Host shutoff, characterized by a global decline of cellular protein synthesis, is commonly observed in many viral infections, including vaccinia virus (VACV). Classic methods measuring host shutoff include the use of radioactive or nonradioactive probes to label newly synthesized proteins followed by radioautography or sodium dodecyl-sulfate polyacrylamide gel electrophoresis to resolve the proteins for follow-up detection. Although these are highly reliable methods, they are time- and labor-consuming. Read More

View Article and Full-Text PDF

Single Immunization with Recombinant ACAM2000 Vaccinia Viruses Expressing the Spike and the Nucleocapsid Proteins Protects Hamsters against SARS-CoV-2-Caused Clinical Disease.

J Virol 2022 May 12;96(9):e0038922. Epub 2022 Apr 12.

Viral Diseases Division, National Microbiology Laboratory, Public Health Agency of Canadagrid.415368.d, Winnipeg, Manitoba, Canada.

Increasing cases of SARS-CoV-2 breakthrough infections from immunization with current spike protein-based COVID-19 vaccines highlight the need to develop alternative vaccines using different platforms and/or antigens. In this study, we expressed SARS-CoV-2 spike and nucleocapsid proteins based on a novel vaccinia virus (VACV) ACAM2000 platform (rACAM2000). In this platform, the vaccinia virus host range and immunoregulatory gene E3L was deleted to make the virus attenuated and to enhance innate immune responses, and another host range gene, K3L, was replaced with a poxvirus ortholog gene, taterapox virus 037 (TATV037), to make virus replication competent in both hamster and human cells. Read More

View Article and Full-Text PDF

Inhibition of VRK1 suppresses proliferation and migration of vascular smooth muscle cells and intima hyperplasia after injury via mTORC1/β-catenin axis.

BMB Rep 2022 Apr 12. Epub 2022 Apr 12.

Department of Cardiology, The General Hospital of Western Theater Command, Chengdu 610083, China.

Characterized by abnormal proliferation and migration of vascular smooth muscle cells (VSMCs), neointima hyperplasia is a hallmark of vascular restenosis after percutaneous vascular interventions. Vaccinia-related kinase 1 (VRK1) is a stress adaption-associated ser/thr protein kinase that can induce the proliferation of various types of cells. However, the role of VRK1 in the proliferation and migration of VSMCs and neointima hyperplasia after vascular injury remains unknown. Read More

View Article and Full-Text PDF

UV Irradiation of Vaccinia Virus-Infected Cells Impairs Cellular Functions, Introduces Lesions into the Viral Genome, and Uncovers Repair Capabilities for the Viral Replication Machinery.

J Virol 2022 May 11;96(9):e0213721. Epub 2022 Apr 11.

Departments of Biochemistry and Molecular Biology, Medical University of South Carolinagrid.259828.c, Charleston, South Carolina, USA.

Vaccinia virus (VV), the prototypic poxvirus, encodes a repertoire of proteins responsible for the metabolism of its large dsDNA genome. Previous work has furthered our understanding of how poxviruses replicate and recombine their genomes, but little is known about whether the poxvirus genome undergoes DNA repair. Our studies here are aimed at understanding how VV responds to exogenous DNA damage introduced by UV irradiation. Read More

View Article and Full-Text PDF

New composition of tungsten has a broad range of antiviral activity.

Antivir Chem Chemother 2022 Jan-Dec;30:20402066221090061

Laboratory of Cell Biology and Virology, Institute of Molecular Biology of NAS RA, Yerevan, Armenia.

The water-based combination of two inorganic chemical compounds such as sodium tungstate dihydrate-NaWO × 2HO and Aluminum sulfate octadecahydrate-Al (SO) 3 × 18HO that we have conditionally named 'Vomifal' has a broad antiviral activity in various DNA and RNA viruses, including Human Herpes Virus (HHV), African Swine Fever Virus (ASFV), Vaccinia Virus (VV), Hepatitis C Virus (HCV), Foot and Mouth Disease Virus (FMDV), Influenza A virus (A/Aichi/2/68 (H3N2)). In vitro and In vivo assays in several tissue cultures as well as in laboratory animals, conformed 'Vomifal' has a very low toxicity and the antiviral properties partially are due to its ability to induce gamma-IFN. Based on the results obtained, we can assume the presence of at least two mechanisms of the antiviral action of the studied drug. Read More

View Article and Full-Text PDF