Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.7 (DNA polymerase)
17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hybridization of DNA probe, obtained through DNA polymerase-mediated in vitro transcription of tick-borne encephalitis virus (TBEV) RNA, with DNA isolated from persistently infected with TBEV cell culture revealed 5.4 copies of viral genome per haploid set.
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PMID:Tick-borne encephalitis virus-specified sequences in persistently infected cell culture revealed by DNA-DNA hybridization. 37 34

Polymerase chain reaction (PCR) was prospectively performed with cerebrospinal fluid (CSF) from 51 patients whose CSF was available for analysis and was submitted for viral culture and/or herpes simplex virus (HSV) serology and 20 patients whose CSF was submitted exclusively to the Clinical Biochemistry Laboratory. Primers were used that flanked a 92 bp segment of the HSV DNA polymerase gene (35 cycles). Amplified products were electrophoresed on agarose gel, blotted onto nylon membrane, and probed with a 32P-labelled sequence internal to the primers. For nested PCR, 1 microliter of PCR product was amplified for an additional 35 cycles before electrophoresis and Southern blot analysis. Review of the clinical records revealed that 15 patients had central nervous system (CNS) infections. Specific HSV DNA sequences were detected in CSF specimens of three of the individuals [PCR(2), nested PCR(1)]. Two of these patients had disseminated HSV infection including encephalitis and one patient had aseptic meningitis. The diagnoses of the 12 patients with CNS infection who did not have HSV DNA detected in CSF included encephalitis [varicella-zoster virus (1), cytomegalovirus (1), Mycoplasma pneumoniae (1)], meningitis [Neisseria meningitidis (1), Coccidioides immitis (1), Enterovirus (1), aseptic meningitis (1)], varicella-zoster radiculitis (2), human immunodeficiency virus dementia (2), and transverse myelitis due to Epstein-Barr virus (1). Importantly, HSV DNA was also not detected in the CSF of the 36 patients who did not have CNS infection and 20 samples submitted exclusively to the Clinical Biochemistry Laboratory. Our findings demonstrate the utility of PCR as a rapid, non-invasive method for the routine laboratory diagnosis of CNS infection due to HSV.
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PMID:A prospective study of the polymerase chain reaction for detection of herpes simplex virus in cerebrospinal fluid submitted to the clinical virology laboratory. 133 47

A single pair of oligonucleotide primers selected within a highly conserved region of the DNA polymerase gene of the herpesviruses was designed to amplify related viral genomes, i.e., herpes simplex virus type 1, herpes simplex virus type 2, Epstein-Barr virus, and cytomegalovirus, by the polymerase chain reaction. A simple restriction enzyme analysis of these amplified products allowed accurate characterization of the herpesvirus type. Ninety-nine cerebrospinal fluid samples from 36 patients (including newborns, children, and adults) with acute encephalitis were tested for the presence and identification of herpesvirus DNA by this approach. High levels of viral DNA, which were readily visualized by simple ethidium bromide staining, were found in all these patients from the first days of the disease and, in some cases, until the third week following the onset of acute encephalitis. The herpesvirus type was rapidly identified by enzymatic digestion in 33 patients' samples and by hybridization and direct sequencing in the last 3 patients' samples. Our results show that the polymerase chain reaction provides a highly sensitive and specific technique for the identification of herpesviruses DNA in cerebrospinal fluid that should be of value for early and rapid diagnosis, therapeutic decisions, prognostic evaluation, and epidemiological studies.
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PMID:Amplification and characterization of herpesvirus DNA in cerebrospinal fluid from patients with acute encephalitis. 166 8

A study was undertaken to determine whether genes associated with herpes simplex virus (HSV) neuroinvasiveness in mice influence the growth of HSV in man, the virus's natural host. HSV-2(186), a nonneuroinvasive HSV strain, was found to replicate poorly (less than 3-fold) in cultures of phytohemagglutinin (PHA) stimulated human peripheral blood mononuclear cells (PBMC). In contrast, seven other HSV strains all multiplied 40- to 100-fold. The paucity of HSV-2(186) growth in PBMC was not due to a failure of this strain to grow in primary human cells because high titers (greater than 10(8) PFU/ml) were obtained following infection of human foreskin fibroblasts. The genetic basis for the deficient growth was analyzed by marker rescue experiments. Recombinant HSV-2 strains were generated in marker rescue experiments utilizing HSV-2(186) DNA and plasmids containing a cloned DNA polymerase gene isolated from a neuroinvasive HSV strain possessing the capacity to replicate in human PBMC. Progeny which rescued DNA from the cloned HSV DNA polymerase gene replicated 40- to 100-fold in PHA-stimulated PBMC. Moreover, unlike the HSV-2(186) parent, HSV-2(186) isolates possessing rescued DNA grew well in the eye, trigeminal ganglion, and brain of mice and induced fatal encephalitis. The results indicate that nucleotide sequences responsible for increasing the capacity of HSV-2(186) to grow in PBMC of man are identical to those responsible for increasing the capacity of this strain to grow in mouse tissues and to spread from the eye to the brain.
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PMID:Nucleotide sequences responsible for the inability of a herpes simplex virus type 2 strain to grow in human lymphocytes are identical to those responsible for its inability to grow in mouse tissues following ocular infection. 216 Nov 43

Clinically acquired acyclovir resistance in herpes simplex has usually been associated with a deficiency in viral thymidine kinase, which, in turn, has been linked with attenuated virulence in animal models. Diminished pathogenicity in thymidine kinase-deficient isolates has been partly responsible for controversies about the clinical significance of antiviral resistance. We report on a series of resistant virus isolates from a patient who had severe, progressive esophagitis. These isolates had various thymidine kinase activities, ranging from 2.8% to 130% when compared with the activity of the isolate obtained before treatment; the resistant isolate 615 retained enzyme activity as well as neurovirulence in an encephalitis model. Plaque purification showed a heterogeneous mixture containing at least one acyclovir-resistant, foscarnet-resistant plaque isolate (615.8) fully able to phosphorylate acyclovir. The 3.3-kbp BamHI fragment containing most of the DNA polymerase gene from isolate 615.8 was purified and used to successfully transfer both acyclovir and foscarnet resistance. Acquisition of in-vitro acyclovir resistance was associated with progression of clinical disease, as well as with maintenance of pathogenicity in an animal model and at least one mutation in viral DNA polymerase. Patients with herpes simplex infections that progress during acyclovir therapy should be observed for acquisition of resistance in the setting of antiviral chemotherapy; future studies should also consider the presence of heterogeneous virus populations in such patients.
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PMID:Progressive esophagitis from acyclovir-resistant herpes simplex. Clinical roles for DNA polymerase mutants and viral heterogeneity? 255 68

Two herpes simplex virus (HSV) intertypic recombinants were isolated with genomes composed entirely of HSV-2(186) nucleotide sequences except for a 6.0 kb segment of HSV-1(17) DNA positioned between 0.40 and 0.44 map units. Following corneal infection of mice, HSV-1(17) and the two intertypic recombinants spread from infected eyes into the central nervous system and induced a fatal encephalitis. Ocular infection with the HSV-2(186) parent did not lead to detectable amounts of virus in the brain, and none of the mice developed encephalitis. The 6.0 kb HSV-1(17) DNA inserted within the genome of the two intertypic recombinants contained nucleotide sequences involved in DNA replication. These include the HSV-1(17) oriL, the HSV-1(17) gene for DNA polymerase and portions of the HSV-1(17) gene coding for DNA-binding protein ICP8. Thus, our results indicate that the difference in the capacity of HSV-1(17) and HSV-2(186) to spread from the cornea into the CNS is determined solely by nucleotide sequences associated with DNA replication.
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PMID:Nucleotide sequences important in DNA replication are responsible for differences in the capacity of two herpes simplex virus strains to spread from cornea to central nervous system. 303 Jun 43

RNA of a flavivirus, tick-borne encephalitis virus (TBEV; strain Sofjin), was subjected to reverse transcription and the DNA copy was transformed into double-stranded DNA by the action of E. coli DNA-polymerase I (Klenow fragment). This DNA was annealed with plasmid pBR322. The recombinant plasmids were cloned in E. coli K802. The nucleotide sequence of the inserts of the clones, coding for region structural proteins C, M, E and nonstructural protein NS1, was determined by the Maxam-Gilbert method. The genes of structural proteins form a compact cluster. Homology has been studied of the TBEV sequences found with the structures of proteins and RNAs of other flaviviruses, yellow fever virus and West Nile virus, and a high degree of homology was found.
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PMID:Tick-borne encephalitis virus genome. The nucleotide sequence coding for virion structural proteins. 370 96

Acyclovir (ACV) has been shown to inhibit the replication of herpes simplex virus (HSV) in vitro. We examined a wide variety of HSV clinical isolates for the presence of naturally occurring ACV-resistant (ACVr) variants. Although the ACV doses that inhibited 50% of these isolates were within the range of doses inhibiting 50% of the ACV-susceptible wild-type strains, we successfully isolated variants resistant to high ACV concentrations (25 to 75 microM) from each virion population even in the absence of prior drug exposure. Furthermore, we demonstrated, by fluctuation analysis of two encephalitis strains, that the ACVr variants were clonally distributed in the virus populations before exposure to ACV and did not result from rapid adaptation to ACV. All variants isolated after a single exposure to a high dose of ACV were true ACVr variants, as demonstrated by their plating efficiencies in the presence of ACV. We found that 36 and 50% of the ACVr variants of the two strains examined in detail displayed plating efficiencies in phosphonoacetic acid of greater than 0.1, possibly indicating that many of the ACVr variants contained alterations in the DNA polymerase gene locus. Because the distribution of ACVr variants in natural populations is relatively high (10(-4), these results suggest that selection of ACVr strains during ACV therapy is possible.
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PMID:Herpes simplex virus variants restraint to high concentrations of acyclovir exist in clinical isolates. 628 42

A virus (151) isolated from synovial membrane explant cultures from a goat with arthritis-synovitis was characterised with respect to cytopathic effect in synovial membrane cell cultures, virus morphology, buoyant density and presence of RNA dependent DNA polymerase. Virus 151 was shown to be a retrovirus with similar properties to caprine arthritis-encephalitis virus in the United States of America. Inoculation of the virus into uninfected goats caused the development of arthritis-synovitis lesions and the virus was recovered from affected joints and lung 361 days post-inoculation. The development of antibody to virus 151 was detected using an enzyme linked immunosorbent assay (ELISA). Other goats with arthritis-synovitis, progressive pneumonia or viral leukoencephalomyelitis all had antibody that reacted in this ELISA. Viruses similar to virus 151 were recovered from a number of cases. Goats inoculated with one of the viruses produced serum antibody that cross-reacted in ELISA using maedi-visna virus and virus 151 as antigens.
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PMID:Characterisation, experimental infection and serological response to caprine retrovirus. 632 Jul 90

Acyclovir is a new antiviral drug that acts as a specific inhibitor of herpesvirus DNA polymerase. It shows good in vitro activity against herpes simplex and varicella-zoster viruses. The drug may be administered topically to the skin, intravenously, orally, or topically to the eye (only topical and intravenous preparations are currently available). Acyclovir kinetics are described by a two-compartment open model. The drug and its metabolites are excreted by the kidney via glomerular filtration and tubular secretion. Dosage adjustment is required in patients with renal failure. Safety and tolerance studies in animals and humans have shown acyclovir to be very well tolerated. The most important adverse effect is crystalluria and elevated serum creatinine related to bolus intravenous administration. Other reported adverse effects include infusion site inflammation and rash. Topical acyclovir is effective for treating initial genital herpes and mucocutaneous herpes in the compromised host, but has not been shown to be clinically useful for recurrent labial or genital herpes. Intravenous acyclovir is effective for mucocutaneous herpes infections in the compromised host and initial genital herpes in the normal host; it is being evaluated for the treatment of herpes simplex virus encephalitis and varicella-zoster infections. An investigational oral preparation may prove to be effective therapy for both initial and recurrent genital herpes. Acyclovir therapy does not eliminate latent virus or prevent subsequent recurrences.
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PMID:Acyclovir: mechanism of action, pharmacokinetics, safety and clinical applications. 635 82


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