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At least 829 records · Page 46Linked to original sources
PubMed2005

Human cytomegalovirus plasmid-based amplicon vector system for gene therapy.

We have constructed and evaluated the utility of a helper-dependent virus vector system that is derived from Human Cytomegalovirus (HCMV). This vector is based on the herpes simplex virus (HSV) amplicon system and contains the HCMV orthologs of the two cis-acting functions required for replication and packaging of HSV genomes, the complex HCMV viral DNA replication origin (oriLyt), and the cleavage packaging signal (the a sequence). The HCMV amplicon vector replicated independently and was packaged into infectious virions in the presence of helper virus. This vector is capable of delivering and expressing foreign genes in infected cells including progenitor cells such as human CD34+ cells. Packaged defective viral genomes were passaged serially in fibroblasts and could be detected at passage 3; however, the copy number appeared to diminish upon serial passage. The HCMV amplicon offers an alternative vector strategy useful for gene(s) delivery to cells of the hematopoietic lineage.

Journal Article↗
PubMed1997

RNA-protein interactions in the regulation of coronavirus RNA replication and transcription.

Coronavirus, with a 31-kb RNA genome, replicates its own RNA and transcribes subgenomic mRNAs by complex mechanisms. Viral RNA synthesis is regulated by multiple RNA regions, which appear to interact either directly or indirectly. Multiple cellular proteins bind to these regions and may undergo additional protein-protein interactions. These findings suggest that coronavirus RNA synthesis is carried out on a ribonucleoprotein via a mechanism that involves both viral and cellular proteins associated with viral RNA, similar to DNA-dependent RNA transcription. This mode of RNA synthesis may be applicable to most RNA viruses.

Animals↗
PubMed1998

Genetic control of host resistance to flavivirus infection in animals.

Flaviviruses are small, enveloped RNA viruses which are generally transmitted by arthropods to animals and man. Although flaviviruses cause important diseases in domestic animals and man, flaviviral infection of animals which constitute the normal vertebrate reservoir may be mild or sub-clinical, which suggests that some adaptation between virus and host may have occurred. While this possibility is difficult to study in wild animals, extensive studies using laboratory mice have demonstrated the existence of innate, flavivirus-specific resistance. Resistance is heritable and is attributable to the gene Flvr, which is located on chromosome 5 in this species. The mechanism of resistance is at present unknown, but acts early and limits the replication of flaviviruses in cells. While some evidence supports a role for Flvr in enhancing the production of defective interfering virus, thereby restricting the production of infectious virus, other reports suggest that Flvr interferes with either virus RNA replication or RNA packaging. Recent research suggests that cytoplasmic proteins bind to the viral replication complex and that allelic forms of these proteins in resistant mice may restrict the production of infectious progeny. Apparent resistance to flaviviruses has been described in other vertebrates, although it remains to be seen if this is attributable to a homologue of Flvr. Nonetheless, knowledge gained of the characteristics and function of Flvr in mice should be applicable to other host species, and improvement of resistance to flaviviral infection in domestic animals by selective breeding or gene technology may ultimately be possible.

Animals↗
PubMed2004

Use of DNA microarrays to monitor host response to virus and virus-derived gene therapy vectors.

Given the biological complexity of viral infections, the variability of the host response, and the safety concerns related to viral-mediated gene transfer, recent studies have made use of DNA mircoarrays to integrate multi-layered experimental approaches aimed at completely clarifying virus-host interactions. Particular attention has been given to those viruses that are implicated in clinical use and/or in life-threatening diseases. Examples of such use can be divided into three main categories, including: (i) the use of microarrays to study viral expression; (ii) the use of microarrays to analyze the host response to viral infection; and (iii) the use of microarrays to characterize the host response to viral vector-mediated transduction. Significant information on virus- and viral vector-host interactions can be obtained with the microarray approach, including the recognition of master pathways of virally-induced responses, the identification of new target genes for specific viruses, and indications on the molecular toxicity of specific gene transfer vectors currently used for gene therapy trials (in particular, adeno-associated viruses and adenovirus-derived vectors). We predict that the development of accessible repositories containing most of the DNA microarray data on viral infections will certainly help to elucidate the puzzling pictures of different viral infections. This will be crucially important for the correct handling of viral diseases and the intelligent amelioration of viral vectors for gene therapy.

Animals↗
PubMed2006

[Molecular mechanism of replication and transcription of the influenza virus genome and host factors].

The genome of influenza A virus is a set of eight segmented- and single-stranded RNAs. A basic transcription and replication unit is the genome complexed with viral RNA-dependent RNA polymerases and nucleoprotein (NP). For the efficient transcription and replication of the genome, not only viral factors but also host cell-derived factors are required. Although receptor and protease molecules play important roles in infection and pathogenicity, it is also possible that host factors involved in the virus genome function determine these. PB2, for instance, is reported to be a possible candidate for determination of the host range of avian influenza viruses. Here we summarize recent progresses in the molecular mechanism of the influenza virus genome transcription and replication and discuss the involvement of host factors in these processes.

Animals↗
PubMed2006

The interaction of G-CSF with its receptor.

The function of the G-CSF receptor has been of considerable interest, particularly because of the clinical usefulness of G-CSF. The first step in receptor activation, which is the interaction of G-CSF with its receptor, has been studied by mapping the binding sites of neutralizing antibodies, by studying the complexes formed between G-CSF and various receptor fragments in solution and by mutagenesis of the receptor and ligand. In addition, the structure of G-CSF has been determined. Part of the ligand-binding domain of the receptor in complex with G-CSF has been crystallized and its structure described. Consideration of all these studies has allowed us to make a model of the complete ligand-binding domain in complex with G-CSF that accounts for the published data. The complex has a 2:2 stoichiometry, with two binding sites on both the ligand and receptor that are equivalent to site II and site III of the IL-6 receptor complex. This model was based on the published structure of gp130 in complex with viral IL-6, which we believe to be very similar.

Binding Sites↗
PubMed2004

Beta-catenin associates with human parainfluenza virus type 3 ribonucleoprotein complex and activates transcription of viral genome RNA in vitro.

Several studies have indicated that human parainfluenza virus type 3 (HPIV-3) requires polymeric actin for transcription of its genome RNA in vitro and in vivo. In the current study, we have identified beta-catenin, an actin-bound protein, as one of the transcriptional activators for HPIV-3 genome RNA. Beta-catenin was packaged within the purified HPIV-3 virions and was associated with the HPIV-3 ribonucleoproteins (RNP) from infected cells. Moreover, purified beta-catenin interacted with bacterially expressed HPIV-3 nucleocapsid protein (N) and phosphoprotein (P) fused to glutathione S-transferase (GST). Double-labeled immunofluorescent confocal microscopic analysis revealed colocalization of beta-catenin with HPIV-3 RNP at cell periphery in infected cells. The HPIV-3 RNP-associated beta-catenin functioned as a transactivator of HPIV-3 genome, because purified beta-catenin stimulated transcription of viral RNP in an in vitro transcription assay. These results demonstrate that beta-catenin, a multifunctional protein that is involved in cell-cell adhesion and embryogenesis, acts as one of the transcriptional activators of HPIV-3 genome RNA.

Cytoskeletal Proteins↗
PubMed2000

Rapid reconstitution of Epstein-Barr virus-specific T lymphocytes following allogeneic stem cell transplantation.

Epstein-Barr virus (EBV)-specific CD8 T lymphocytes are present at remarkably high frequencies in healthy EBV(+) individuals and provide protection from EBV-associated lymphoproliferative diseases. Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) is a commonly used therapy in which T-cell surveillance for EBV is temporarily disrupted. Herein, human leukocyte antigen (HLA) class I tetramers were used to investigate the reestablishment of the EBV-specific CD8 T-cell repertoire in patients following allo-PBSCT. CD8(+) T cells specific for lytic and latent cycle-derived EBV peptides rapidly repopulate the periphery of matched sibling allo-PBSCT patients. The relative frequencies of T cells specific for different EBV peptides in transplantation recipients closely reflect those of their respective donors. Investigation of patients at monthly intervals following unmanipulated allo-PBSCT demonstrated that the frequency of EBV-specific T cells correlates with the number of EBV genome copies in the peripheral blood and that expansion of EBV-specific T-cell populations occurs even in the setting of immunosuppressive therapy. In contrast, patients undergoing T-cell-depleted or unrelated cord blood transplantation have undetectable EBV-specific T cells, even in the presence of Epstein-Barr viremia. The protective shield provided by EBV-specific CD8 T cells is rapidly established following unmanipulated matched sibling allo-PBSCT and demonstrates that HLA class I tetramers complexed with viral peptides can provide direct and rapid assessment of pathogen-specific immunity in this and other vulnerable patient populations. (Blood. 2000;96:2814-2821)

Adult↗
PubMedDate not supplied

[Possibilities of complex etiological diagnosis of chronic viral hepatitides B and C].

Etiological markers for HBV and HBC were studied in 26 cases of chronic hepatitis. In 21 cases coincidence of serological and immunohistochemical results was found, in 9 cases markers of other viruses were registered. Immunohistochemical markers were identified in 3 of 5 liver biopsies in patients with negative serological tests. Histological signs of HBV and HBC corresponded to those of serological and immunohistochemical ones in 17 cases.

Female↗
PubMed2005

Pharmacokinetics of plasmid DNA-based non-viral gene medicine.

Non-viral gene therapy can be realized by optimization of the pharmacokinetic properties of both the vector and the encoded therapeutic protein. A major obstacle to its successful clinical application is the limited ability of plasmid DNA, the most convenient gene-coding compound, to distribute within the body after in vivo administration. Under normal conditions, plasmid DNA and its non-viral vector complexes have difficulty in passing through various anatomical and biological barriers. These characteristics greatly limit the number and distribution of cells transduced with the vector, because transgene expression only occurs in cells that are reached by the vector. New approaches to the design of vectors as well as the methods of administration, such as electroporation and a hydrodynamic delivery, have increased the transgene expression in vivo, suggesting that improved distribution of plasmid DNA is possible by these approaches. In this chapter, the basic pharmacokinetic properties of naked plasmid DNA under normal conditions are first reviewed, then the properties of both naked and complexed plasmid DNA are discussed under conditions where significant transgene expression takes place.

DNA↗
PubMed2006

Epidemiology, natural history, and treatment of hepatitis B virus and hepatitis C virus coinfection.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important global public health problems. Coinfection with HBV and HCV is not uncommon due to the shared route of parenteral transmission. The interaction between HBV and HCV in coinfected individuals is complex, and viral interference has been well described. Patients who are coinfected with HBV and HCV have faster rates of fibrosis progression, more severe liver disease, and are at markedly increased risk of developing hepatocellular carcinoma as compared to those with HBV or HCV monoinfection. Therefore, treatment of HBV-HCV coinfection is important, but it is a challenging and evolving field. Hepatitis A virus (HAV) superinfection is associated with a high risk of liver failure and death in patients with underlying chronic liver disease, and all individuals with HBV-HCV coinfection should receive the HAV vaccine.

Hepacivirus↗
PubMed1990

Virology of the human immunodeficiency virus type 1.

Understanding the mode of replication of the human immunodeficiency virus (HIV) is necessary for explaining the natural history of HIV infection and for the development of therapeutic and prophylactic agents. The life cycle of HIV involves infective particles, the attachment of the virus to specific cell receptors, reverse transcription of the viral RNA into DNA by using viral encoded enzymes, integration of the viral DNA into the host genome, use of the host machinery to transcribe and translate viral genes, and the formation of budding particles. Viral encoded genes, regulated by a complex interaction of viral and host proteins with viral sequences, ultimately encode for the viral structural proteins, regulatory proteins, and enzymes necessary for the formation of mature infectious particles. Blocking one or more steps in the viral life cycle and preventing enhancement of virus production are important approaches in the control of HIV.

Acquired Immunodeficiency Syndrome↗