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Mechanisms of Attenuation by Genetic Recoding of Viruses.

The development of safe and effective vaccines against viruses is central to disease control. With advancements in DNA synthesis technology, the production of synthetic viral genomes has fueled many research efforts that aim to generate attenuated viruses by introducing synonymous mutations. Elucidation of the mechanisms underlying virus attenuation through synonymous mutagenesis is revealing interesting new biology that can be exploited for vaccine development. Here, we review recent advancements in this field of synthetic virology and focus on the molecular mechanisms of attenuation by genet

Applications of nanoparticles for DNA based rabies vaccine.

Rabies is a fatal encephalomyelitis. Most cases occur in developing countries and are transmitted by dogs. The cell culture vaccines as associated with high cost; therefore, have not replaced the unsafe brain-derived vaccines. In the developing countries these brain-derived rabies vaccines still can be seen in action. Moreover, there will be a need for vaccines against rabies-related viruses against which classical vaccines are not always effective. The worldwide incidence of rabies and the inability of currently used vaccination strategies to provide highly potent and cost-effective therapy i

Bombyx mori lipase-1 reduces viral replication and proliferation by inhibiting the expression of the DNA-binding protein (dbp) gene.

Bombyx mori lipase-1 (Bmlipase-1) has strong anti-BmNPV activity, but the mechanism by which Bmlipase-1 resists BmNPV invasion has not been elucidated so far. In this paper, based on the construction of recombinant viruses overexpressing Bmlipase-1, we analyzed the effects of the recombinant viruses on the genes related to recombinant virus replication as well as viral replication and proliferation after the recombinant viruses infected BmN cells. In the presence of the virus, Bmlipase-1 localizes to the cell nucleus. Quantitative polymerase chain reaction (qPCR), northern blotting and western

Molecular survey of herpesviruses in bats from Chile and Spain reveals potentially novel species.

Bats (order Chiroptera) are known as important hosts and reservoirs for several zoonotic viruses. To this date, most virology studies in bats have focused on RNA viruses; consequently, information about DNA viruses is more limited. Herein we surveyed the presence of herpesviruses in blood or spleen samples of three bat species of Spain (n = 31) and five bat species of Chile (n = 50) by using a broad-spectrum nested PCR. Overall, herpesvirus DNA was detected in 9.7% (3/31) bats of Spain and 10.0% (5/50) bats of Chile. Three gammaherpesvirus sequence types were found in bats from Spain, while se…

Traditional and novel approaches to flavivirus vaccines.

Yellow fever, dengue, Japanese encephalitis and tick-borne encephalitis viruses are the medically most important members of the Flavivirus genus composed primarily of arboviruses. In this paper, we review the commercially available traditional flavivirus vaccines against yellow fever, Japanese encephalitis, and tick-borne encephalitis, as well as modern approaches to flavivirus vaccines. Formalin inactivation technology has been employed to produce killed vaccines. Flaviviruses have been attenuated by multiple passages in animal tissues and cell cultures to produce empirical live attenuated va

Response of homozygous and heterozygous xeroderma pigmentosum cells to several chemical and viral carcinogens.

The topics discussed include the relationship between the carcinogenic property of various compounds and their capacity to elicit DNA damage that results in a DNA repair synthesis; the metabolic activation of precarcinogens; the in vivo use of DNA repair synthesis in the identification of tissues that will give rise to neoplasms; the possible involvement of DNA repair in the sensitivity of human cells to the chromosome-damaging and lethal effect of chemical carcinogens; the different responses of homozygous xeroderma pigmentosum (XP) cells, heterozygous XP cells, and controls to some but not a

Association of neurotropic viruses in HIV-infected individuals who died of secondary complications of tuberculosis, cryptococcosis, or toxoplasmosis in South India.

The frequencies of 10 opportunistic DNA viruses were determined by multiplex real-time PCR in paired cerebrospinal fluid (CSF) and brain tissue of HIV-infected individuals. In the CSF, viruses were detectable in 45/55 cases: JC virus (JCV) in 62%, Epstein-Barr virus (EBV) in 44%, cytomegalovirus (CMV) in 25%, varicella-zoster virus (VZV) in 3.6%, herpes simplex virus 1 (HSV-1) in 1.8%, and human herpesvirus 6 (HHV-6) in 1.8% of cases. A single virus was detectable in 20 cases, 19 cases had coinfection with two viruses, and 6 cases were positive for three viruses. JCV was detectable in the CSF …

Poliovirus antigen chimeras.

Poliovirus, the aetiological agent of paralytic poliomyelitis, is arguably the best characterized of all animal viruses. Using recombinant-DNA technology, this information, together with the availability of infectious cDNA clones of the notably safe and efficacious live attenuated Sabin 1 vaccine strains of poliovirus, has enabled the creation of hybrid viruses (chimeras) possessing novel antigenicity. The potential applications of these 'epitope-presentation systems' include their use as immunogens, as antigens for serodiagnosis, and as vaccines.

Characterization, Directed Evolution, and Targeting of DNA Virus-Encoded RNA Capping Enzymes Using Phenotypic Yeast Platforms.

The constant and the sudden emergence of zoonotic human and animal viruses is a significant threat to human health, the world economy, and t … haracterize, and target viral genome-encoded essential RNA capping enzymes from emerging strains of DNA viruses, i.e., Monkeypox virus and African Swine Fever Virus, which are a significant threat to human and domestic animal health. We first identified and biochemically characterized these viral RNA capping enzymes and their necessary protein domains. We obs …

F-coliphages, porcine adenovirus and porcine teschovirus as potential indicator viruses of fecal contamination for pork carcass processing.

There are concerns about the zoonotic transmission of viruses through undercooked pork products. There is a lack of information on suitable indicator viruses for fecal contamination with pathogenic enteric viruses in the meat processing chain. The study compared the incidence and levels of contamination of hog carcasses with F-coliphages, porcine teschovirus (PTV), and porcine adenovirus (PAdV) at different stages of the dressing process to assess their potential as indicator viruses of fecal contamination. One hundred swab samples (200cm2) were collected from random sites on hog carcasses at

Maternal contact and age-dependent succession influence the assembly of the calf rumen microbiome and virome.

Early-life colonization of the rumen is particularly important; however, the processes by which microbial and viral communities are transmit … evealing extensive microbial and viral novelty. Our analyses demonstrated that both prokaryotes and DNA viruses are shared between dams and calves, with greater sharing observed in calves raised with maternal contact than in calves raised without maternal contact. Notably, viral sharing between cow-calf pairs was markedly lower compared to prokaryotes, sugges …

Sp140L функционирует как фактор ограничения герпесвируса, подавляющий вирусную транскрипцию и активирующий интерферонально-стимулированные гены.

Герпесвирусы, включая вирус Эпштейн-Барр (ЭБВ), - человеческий онкогенный вирус и важнейший пусковой механизм множественного склероза, - должны обходить механизмы ДНК-разведки, чтобы установить пожизненную скрытую инфекцию. Поэтому герпесвирусы кодируют вирусные белки, чтобы разрушить ключевые факторы, связанные с зондированием ДНК и вирусным ограничением. Первый вирусный белок латентности, выраженный EBNA-LP, крайне важен для преобразования наивных клеток B и установления вирусного генного экспрессии, однако его роль в уклонении от защиты хостов остается неясной. Используя одноклеточную после

Совпадение в аннотации оригинала
Herpesviruses, including Epstein-Barr virus (EBV) - a human oncogenic virus and essential trigger of multiple sclerosis - must bypass host D … et of the herpesvirus saimiri ORF3 protein, implying a role for Sp140L in immunity to other diverse DNA viruses. This study reveals Sp140L as a restriction factor that we propose links sensing and transcriptional suppression of viral DNA to an Interferon-independent innate immune response, likely relevant to all nuclear DNA viruses.

Association of HPV with human genital tumors.

Human papillomaviruses (HPV) are clearly responsible for the induction of genital lesions like condylomata acuminata, bowenoid papules, and flat condylomas. Moreover, the DNA of particular virus types (HPV 16 and 18) is found in a substantial number of invasively growing squamous cell carcinomas of the genital tract, suggesting an etiologic involvement of these viruses in tumor development. Since HPV 16 and 18 as well as other papillomaviruses (HPV 6 or 11) usually present within the benign genital warts can be found in dysplastic lesions of the uterine cervix known as putative precancerous le

Fragment Size-Based Enrichment of Viral Sequences in Plasma Cell-Free DNA.

Sequencing of plasma cell-free DNA (cfDNA) is a promising milieu for broad-based cancer and infectious disease diagnostics. The performance … It shows that the shorter plasma cfDNA fragment size distribution is a general feature of multiple DNA viruses, including adenovirus [interquartile range (IQR), 87 to 165 bp], herpes simplex virus 2 (IQR, 114 to 195 bp), human herpesvirus 6 (IQR, 145 to 176 bp), and varicella zoster virus (IQR, 98 to 182 bp), compared with human (IQR, 148 to 178 bp). It was …

Targeting human oncogenic viruses with CRISPR/Cas: New therapeutic opportunities and challenges.

CRISPR/Cas systems, initially characterized as bacterial adaptive immune mechanisms, have rapidly emerged as precise and versatile genome-ed … ng of viral transcripts, and modulation of host tumor-suppressor pathways. Cas9 efficiently targets DNA viruses, such as HBV and HPV, whereas RNA-targeting Cas13 allows precise silencing of RNA viruses, like HCV. Editing T-cell receptors, including CCR5 and CXCR4, offers the potential for long-term resistance to HIV. CRISPR-based preclinical studies indicate …

Development and application of multiplex PCR method for simultaneous detection of seven viruses in ducks.

BACKGROUND: Major viruses, including duck-origin avian influenza virus, duck-origin Newcastle disease virus, novel duck parvovirus, duck hepatitis A virus, duck Tembusu virus, fowl adenovirus, and duck enteritis virus, pose great harm to ducks and cause enormous economic losses to duck industry. This study aims to establish a multiplex polymerase chain reaction (m-PCR) method for simultaneous detection of these seven viruses. RESULTS: Specific primers were designed and synthesized according to the conserved region of seven viral gene sequences. Then, seven recombinant plasmids, as the positiv

A novel approach to propagate flavivirus infectious cDNA clones in bacteria by introducing tandem repeat sequences upstream of virus genome.

Despite tremendous efforts to improve the methodology for constructing flavivirus infectious cDNAs, the manipulation of flavivirus cDNAs remains a difficult task in bacteria. Here, we successfully propagated DNA-launched type 2 dengue virus (DENV2) and Japanese encephalitis virus (JEV) infectious cDNAs by introducing seven repeats of the tetracycline-response element (7×TRE) and a minimal cytomegalovirus (CMVmin) promoter upstream of the viral genome. Insertion of the 7×TRE-CMVmin sequence upstream of the DENV2 or JEV genome decreased the cryptic E. coli promoter (ECP) activity of the viral ge

A Novel 2-dimensional Multiplex qPCR Assay for Single-Tube Detection of Nine Human Herpesviruses.

Human herpesviruses are double-stranded DNA viruses that are classified into nine species. More than 90% of adults are ever infected with one or more herpesviruses. The symptoms of infection with different herpesviruses are diverse ranging from mild or asymptomatic infections to deadly diseases such as aggressive lymphomas and sarcomas. Timely and accurate detection of herpesvirus infection is critical for clinical management and treatment. In this study, we established a single-tube nonuple qPCR assay for detection of all nine herpesviruses using a 2-D multiplex qPCR method with a house-keepi…

Protein/DNA polyplexes for gene therapy.

The development of molecular conjugates as components of Protein/DNA polyplexes has resulted in the creation of a simple, non-virus vector for the targeted delivery of nucleic acids into specific cell types. This vector has many of the positive attributes of viruses, on without the limitations that continue to plague recombinant viruses. The simplicity of this vector allows for quick analysis of nucleic acids, expression vectors, and therapeutic genes in vitro and potentially in vivo, because the time that would be involved in the generation of recombinant viral vectors is not present. Essenti

Oncolytic Virotherapy for Cancer: Clinical Experience.

Oncolytic viruses are a new class of therapeutics which are largely in the experimental stage, with just one virus approved by the FDA thus … es of clinical trials. Other oncolytic viruses that have been studied in clinical trials are mostly DNA viruses that belong to one of the three families: herpesviridae, poxviridae or adenoviridae. In this review work we discuss recent clinical studies with oncolytic viruses, especially herpesvirus, poxvirus, adenovirus and reovirus. In summary, the oncolytic …