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protease-dependent uncoating of a complex retrovirus.although retrovirus egress and budding have been partly unraveled, little is known about early stages of the replication cycle. in particular, retroviral uncoating, a process during which incoming retroviral cores are altered to allow the integration of the viral genome into host chromosomes, is poorly understood. to get insights into these early events of the retroviral cycle, we have used foamy complex retroviruses as a model. in this report, we show that a protease-defective foamy retrovirus ...200515994819
retroviral superinfection resistance.the retroviral phenomenon of superinfection resistance (sir) defines an interference mechanism that is established after primary infection, preventing the infected cell from being superinfected by a similar type of virus. this review describes our present understanding of the underlying mechanisms of sir established by three characteristic retroviruses: murine leukaemia virus (mulv), foamy virus (fv), and human immunodeficiency virus (hiv). in addition, sir is discussed with respect to hiv super ...200516107223
improved purification protocol for wild-type and mutant human foamy virus proteases.wild-type and an active site mutant (s25t) human foamy virus (hfv) proteases were expressed in fusion with maltose binding protein in escherichia coli. the mutant enzyme contained a ser to thr mutation in the -asp-ser-gly- active site triplet of the enzyme, which forms the "fireman's grip" between the two subunits of the homodimeric enzyme. the fusion proteins were purified by affinity chromatography on amylose resin, cleaved with factor xa, and the processed enzymes were purified by gel filtrat ...200616243539
antibodies against gag are diagnostic markers for feline foamy virus infections while env and bet reactivity is undetectable in a substantial fraction of infected cats.spumaretroviruses or foamy viruses constitute a distinct subfamily of retroviruses. the biology of foamy viruses within the authentic host, their mode of transmission, and disease potential in the authentic host or after zoonotic transmission into human or other species are almost unknown. using feline foamy virus (ffv) as model system, we established modular enzyme-linked immunosorbent assays (elisa) suited to determine feline igg and igm antibody responses against structural and non-structural ...200616297422
human foamy virus bel1 sequence in patients with autoimmune rheumatic diseases.since the association between human foamy virus (hfv) with rheumatic autoimmune diseases remains controversial, this study was designed to determine the relationship between hfv and systemic lupus erythematosus (sle), rheumatoid arthritis (ra), or progressive systemic sclerosis (pss). the bel1 and pol sequences of hfv were measured by reverse transcriptase-polymerase chain reaction (rt-pcr) in plasma and by pcr in peripheral blood mononuclear cells (pbmc) from patients with sle, ra, and pss. ant ...200616365688
effect of mutations on the dimer stability and the ph optimum of the human foamy virus protease.to explore the role of residues being close to the catalytic aspartates in the higher ph optimum and in the lower dimer stability of human foamy virus (hfv) protease (pr) in comparison with human immunodeficiency virus type 1 (hiv-1) protease, single (q8r, h22l, s25t, t28d) and double (q8r-t28d, h22l-t28d) mutants were created based on sequence alignments and on the molecular model of hfv pr. the wild-type and mutant enzymes were expressed in fusion with maltose binding protein in escherichia co ...200616799151
acetylation of the foamy virus transactivator tas by pcaf augments promoter-binding affinity and virus transcription.it was shown recently that retrovirus transactivators interact with transcriptional coactivators, such as histone acetyltransferases (hats). foamy viruses (fvs) direct gene expression from the long terminal repeat and from an internal promoter. the activity of both promoters is strictly dependent on the dna-binding transactivator tas. recently, it was shown that tas interacts with the hats p300 and pcaf. based on these findings, it is demonstrated here that pcaf has the ability to acetylate tas ...200717170459
effective inhibition of hepatitis b virus replication by small interfering rnas expressed from human foamy virus vectors.rna interference (rnai) mediated by double- stranded small interfering rna (sirna) is a novel mechanism of sequence-specific, post-transcriptional gene silencing. there has been much research into the use of rnai for the treatment of human diseases. many viruses, including hepatitis b virus (hbv), are susceptible to inhibition by this mechanism. however, for rnai to be efficacious therapeutically, effective rnai targeting sequences and a suitable delivery system are required. in this study, we e ...200717334648
recombinant human foamy virus, a novel vector for neurological disorders gene therapy, drives production of gad in cultured astrocytes.human foamy virus (hfv), with its nonpathogenic nature and several unique features for gene transfer, is a promising vector system for neurological disorders gene therapy. the question of whether hfv vectors can be developed for the expression of therapeutic genes in primary astrocytes of the brain may be of interest. first, efficient expression for foreign genes, which is critical for the potentials of hfv-derived vector in gene therapy, was successfully demonstrated in rat-cultured astrocytes ...200717579580
a novel human foamy virus mediated gene transfer of gad67 reduces neuropathic pain following spinal cord injury.neuropathic pain is a long-lasting clinical problem that is often refractory to medical management. gene transfer of specific genes for therapeutic benefit offers a novel approach to the treatment of neuropathic pain. in this study, we tested whether the transfer of the glutamic acid decarboxylase (gad) gene to dorsal root ganglion (drg) cells would attenuate below-injury level central neuropathic pain after spinal cord injury (sci) by using a novel human foamy virus (hfv) vector to achieve rele ...200818180106
amino acid preferences of retroviral proteases for amino-terminal positions in a type 1 cleavage site.the specificities of the proteases of 11 retroviruses were studied using a series of oligopeptides with amino acid substitutions in the p1, p3, and p4 positions of a naturally occurring type 1 cleavage site (val-ser-gln-asn-tyr downward arrowpro-ile-val-gln) in human immunodeficiency virus type 1 (hiv-1). previously, the substrate specificity of the p2 site was studied for the same representative set of retroviral proteases, which included at least one member from each of the seven genera of the ...200818701588
the c terminus of foamy retrovirus gag contains determinants for encapsidation of pol protein into virions.foamy viruses (fv) differ from orthoretroviruses in many aspects of their replication cycle. a major difference is in the mode of pol expression, regulation, and encapsidation into virions. orthoretroviruses synthesize pol as a gag-pol fusion protein so that pol is encapsidated into virus particles through gag assembly domains. however, as fv express pol independently of gag from a spliced mrna, packaging occurs through a distinct mechanism. fv genomic rna contains cis-acting sequences that are ...200818715914
species-specific inhibition of apobec3c by the prototype foamy virus protein bet.the apobec3 cytidine deaminases are part of the intrinsic defense of cells against retroviruses. lentiviruses and spumaviruses have evolved essential accessory proteins, vif and bet, respectively, which counteract the apobec3 proteins. we show here that bet of the prototype foamy virus inhibits the antiviral apobec3c activity by a mechanism distinct to vif: bet forms a complex with apobec3c without inducing its degradation. bet abolished apobec3c dimerization as shown by coimmunoprecipitation an ...200919074429
[inhibitive effect of human foamy virus induced il-24 on cancer cells].to construct replication-defective hfv-il24 virus vector and to investigate its inhibitive effect on cancer cells after infected or transfected by this vector.201020230669
structural studies of the catalytic core of the primate foamy virus (pfv-1) integrase.retroviral integrases are vital enzymes in the viral life cycle and thus are important targets for antiretroviral drugs. the structure of the catalytic core domain of the integrase from human foamy virus, which is related to hiv-1, has been solved. the structure of the protein is presented in two different crystal forms, each containing several molecules in the asymmetric unit, with and without the essential manganese or magnesium ion, and the structures are compared in detail. this allows regio ...201020693659
foamy retrovirus integrase contains a pol dimerization domain required for protease activation.unlike orthoretroviruses, foamy retroviruses (fv) synthesize pol independently of gag. the fv pol precursor is cleaved only once between reverse transcriptase (rt) and integrase (in) by the protease (pr), resulting in a pr-rt and an in protein. only the pol precursor, not the cleaved subunits, is packaged into virions. like orthoretroviral prs, fv pr needs to dimerize to be active. previously, we showed that a pol mutant lacking in has defects in pr activity and pol packaging into virions. we no ...201021123385
structural and thermodynamic signatures that define pseudotriloop rna hairpins.pseudotriloop (ptl) structures in rnas have been recognized as essential elements in rna folding and recognition of proteins. ptl structures are derived from hexaloops by formation of a cross-loop base pair leaving a triloop and 3' bulged out residue. despite their common presence and functional importance, insufficient structural and thermodynamic data are available that can be used to predict formation of ptls from sequence alone. using nmr spectroscopy and uv-melting data we established facto ...201324158793
the novel landscape of long non-coding rnas in response to human foamy virus infection characterized by rna-seq.human foamy virus (hfv) is a complex and unique retrovirus with the longest genomes among retroviruses that are used as vectors for gene therapy. long non-coding rnas (lncrnas) are regarded as key regulators that are involved in diverse biological processes during viral infection. however, the role of lncrnas in hfv infection remains unknown. in this study, we utilized next-generation sequencing to first characterize lncrnas in 293t cells after hfv infection, evaluating length distribution, exon ...201627750433
a new paradigm about herv-k102 particle production and blocked release to explain cortisol mediated immunosenescence and age-associated risk of chronic disease.the majority of chronic diseases in the aging adult are thought to relate to immune aging characterized by dominant immunosuppression and paradoxically, concomitant inflammation. this is known collectively as immunosenescence. the main change thought to be controlling immune aging is the age-related decline in dehydroepiandrosterone (dhea) and corresponding increase in cortisol; the net effect which decreases the dhea/cortisol ratio. exactly how this translates to immunosuppression and concomita ...201526760982
non-simian foamy viruses: molecular virology, tropism and prevalence and zoonotic/interspecies transmission.within the field of retrovirus, our knowledge of foamy viruses (fv) is still limited. their unique replication strategy and mechanism of viral persistency needs further research to gain understanding of the virus-host interactions, especially in the light of the recent findings suggesting their ancient origin and long co-evolution with their nonhuman hosts. unquestionably, the most studied member is the primate/prototype foamy virus (pfv) which was originally isolated from a human (designated as ...201324064793
complete genome sequences of two novel puma concolor foamy viruses from california.we report two complete foamy retrovirus (fv) genomes isolated from puma concolor, a large cat native to the americas. due to high overall genetic relatedness to known feline foamy viruses (ffvs), we propose the name puma concolor ffv (ffvpc). the data confirm that felines are infected with distinct but closely related fvs.201323516229
relative comparison of catalytic characteristics of human foamy virus and hiv-1 integrases.due to their ability to integrate into the host cell's genome, retroviruses represent an optimal basis for the creation of gene therapy vectors. the integration reaction is carried out by a viral enzyme integrase: thus, a detailed research of this enzyme is required. in this work, the catalytic properties of human foamy virus integrase were studied. this virus belongs to the retroviridae family. the dissociation constant was determined, together with the kinetics of integrase catalytic activity. ...200922649606
improved biosafety of a lentiviral vector by reducing cellular gene activation.lentiviral vectors (lvs) have enhancer activity and/or transcriptional read-through (eatrt) properties that can lead to the activation of adjacent genes. consequently, patients may be at increased risk for adverse effects if such vectors are used clinically.201930901108
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