Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis B viruses establish a chronic, productive, and noncytopathic infection of hepatocytes. Viral products are produced by transcription from multiple copies (5-50) of covalently closed circular (ccc) viral DNA. This cccDNA does not replicate, but can be replaced by DNA precursors that are synthesized in the cytoplasm. The present study was carried out to determine if long-term treatment with an inhibitor of viral DNA synthesis would lead to loss of virus products, including cccDNA, from the liver of woodchucks chronically infected with woodchuck hepatitis virus. Viral DNA synthesis was inhibited with the nucleoside analog, lamivudine (2'-deoxy-3'-thiacytidine). Lamivudine treatment produced a slow but progressive decline in viral titers in serum, to about 0.3% or less of the initial level. However, even after maintenance of drug therapy for 3-12 months, > 95% of the hepatocytes in most animals were still infected. Significant declines in the percentage of infected hepatocytes and of intrahepatic cccDNA levels were observed in only three woodchucks, two in the group receiving lamivudine and one in the placebo control group. Moreover, virus titers eventually rose in woodchucks receiving lamivudine, suggesting that drug-resistant viruses began to spread through the liver starting at least as early as 9-12 months of treatment. Three types of mutation that may be associated with drug resistance were found at this time, in a region upstream of the YMDD motif in the active site of the viral reverse transcriptase. The YMDD motif itself remained unchanged. Not unexpectedly, the lamivudine therapy did not have a impact on development of liver cancer.
 ...
PMID:Lamivudine therapy of WHV-infected woodchucks. 961 64

Hepatitis-associated aplastic anemia (HAAA) is an uncommon disorder that usually is not due to hepatitis A or B virus infection. Hepatitis C virus (HCV) seropositivity is infrequently observed in aplastic anemia (AA) patients who have not been extensively transfused. However, HCV seropositivity may not be detected until several weeks or months after viral infection and AA patients may exhibit defective humoral immunity. Therefore, we evaluated sera from AA patients for the presence of HCV viremia using a reverse transcriptase polymerase chain reaction (RT-PCR) based assay and several serologic assays for HCV antibodies. Serum samples from 90 AA patients who presented to the UCLA Medical Center between March 1984 and February 1990 were analyzed. Overall, 17 patients were found to have HCV viremia by RT-PCR assay, of whom 14 had a positive second-generation HCV enzyme immunoassay (EIA-2) and only 6 were EIA-1 reactive. The frequency of HCV viremia increased with the duration of time between diagnosis and sample procurement, and the number of blood products transfused prior to sampling (P = 0.026). No patient who received fewer than 20 U of blood products or who was sampled less than 20 days after diagnosis had a positive HCV RT-PCR result. Of four patients with hepatitis-associated AA (HAAA), one who was sampled 23 days after diagnosis had hepatitis C viremia and a reactive EIA-2 assay. Therefore, the high frequency of HCV viremia in this patient population is most likely due to transfusion with contaminated blood products prior to the introduction of routine blood donor screening for HCV.
 ...
PMID:Hepatitis C virus infection in acquired aplastic anemia. 962 79

The development of policies to prevent nosocomial transmission of hepatitis C virus (HCV) infection in hemodialysis units is critically dependent on the understanding of the relationship between tests for anti-HCV, HCV RNA, and HCV genotype and the patients' clinical characteristics. We tested sera from all patients on the renal transplant waiting list at the New England Organ Bank between November 1986 and June 1990 for anti-HCV by a third-generation enzyme-linked immunosorbent assay (ELISA3) and a third-generation recombinant immunoblot assay (RIBA3). All ELISA3-positive sera were tested for HCV RNA by reverse transcriptase "nested" polymerase chain reaction, and the genotype was characterized by restriction fragment length polymorphism. Sera were available in 1,544 of 3,243 (48%) patients on the waiting list, of whom 287 (19%) tested positive for anti-HCV by ELISA3. Two hundred eighty-six randomly selected, anti-HCV-negative patients served as controls. Compared with anti-HCV-negative controls, anti-HCV-positive patients had a longer duration since initiation of renal replacement therapy, higher number of previous kidney transplants and blood transfusions, higher proportion of patients with anti-HBc, history of liver disease, history of non-A, non-B hepatitis, and elevated serum alanine aminotransferase, and lower serum albumin concentrations. Of the 287 anti-HCV-positive sera, 261 (91%) were reactive by RIBA3, 21 (7%) were indeterminate, and five (2%) were nonreactive. HCV RNA was detected in 224 of 275 (81%) ELISA3-positive patients, in whom additional sera were available. There were no significant differences in clinical or laboratory characteristics between ELISA3-positive patients with and without HCV RNA. Genotypes 1a, 1b, 2a, 2b, 3a, and 4 were present in 53%, 23%, 8%, 10%, 4%, and 2% of patients, respectively. Infection with one, two, or three different HCV genotypes was present in 92%, 7%, and 1%, respectively. There was no significant association between the type or number of HCV genotypes and RIBA3 reactivity. There were no major differences in clinical or laboratory characteristics between genotypes or between single and mixed infection. In summary, this study provides detailed information regarding the relationship between tests for anti-HCV, HCV RNA, and HCV genotypes and the clinical and laboratory characteristics of a large, well-characterized cohort of patients referred for renal transplant.
 ...
PMID:Serologic and virologic profiles of hepatitis C infection in renal transplant candidates. New England Organ Bank Hepatitis C Study Group. 963 34

Functional analysis of naturally occurring hepatitis B virus (HBV) mutations is crucial in understanding their impact on disease. We have recently identified two mutations in the HBV core promoter of an HBV strain associated with fulminant hepatitis leading to highly (15-fold) enhanced replication as a result of increased viral encapsidation of pregenomic RNA into the core particles (T. F. Baumert et al., J. Clin. Invest. 98:2268-2276, 1996). Functional studies in an encapsidation assay had demonstrated that the increase in encapsidation was largely independent of pregenomic RNA transcription. In this study, we define the molecular mechanism whereby the two core promoter mutations (C to T at nucleotide [nt] 1768 and T to A at nt 1770) result in enhanced viral encapsidation and replication. The effect of these mutations leading to increased encapsidation is mediated through enhanced core protein synthesis (15-fold) by the mutant virus. The marked increase in core protein synthesis is largely a result of posttranscriptional or translational effect of the mutations because the mutations resulted in only a twofold increase in pregenomic RNA transcription. In addition, this effect appears to be selective for core expression since reverse transcriptase-polymerase expression was increased only twofold. trans-complementation analyses of HBV replication demonstrated that enhanced replication occurred only when the mutations were provided together with the core protein in trans, confirming the functional association of the core promoter mutations and core protein expression. In addition, the effect of the mutations appears to be quantitatively dependent on the strain background to which the mutations were introduced. Our study suggests that the HBV core promoter regulates core protein expression at both transcriptional and posttranscriptional levels.
 ...
PMID:Naturally occurring mutations define a novel function of the hepatitis B virus core promoter in core protein expression. 965 27

The clinical significance and course of acute hepatitis G virus (HGV) infection were studied by measuring HGV RNA and antibody to HGV envelope protein E2 (HGV-E2 antibody). A total of 59 patients with transfusion-associated non-A, non-B hepatitis, who were followed-up for more than 1 year, were selected retrospectively. HGV RNA was measured by reverse transcriptase (RT) and nested polymerase chain reaction (PCR) was performed, using primer sets, in the 5'-non-coding region of the HGV genome. HGV-E2 antibody was measured by enzyme-linked immunosorbent assay (ELISA) using recombinant E2 protein. Of the 59 patients, 51 (86%) were infected with hepatitis C virus (HCV) and 12 (20%) were infected with HGV; 11 of the 12 with HGV infection were also infected with HCV. HGV viraemia was cleared during the follow-up period in seven of the 12 patients with HGV infection. All these seven patients seroconverted for HGV-E2 antibody just before or just after the clearance of HGV viraemia. In contrast, all five patients without clearance of HGV viraemia were negative for HGV-E2 antibody (P = 0.0013). Of seven patients with continuous HGV viraemia at 1 year from the onset of acute hepatitis, four with HCV RNA showed chronic elevation of alanine aminotransferase (ALT) but three without HCV RNA did not. The severity of acute hepatitis was similar between patients with both HGV and HCV infections and in those with HCV infection alone. The majority of patients with HGV infection cleared the virus during long-term follow-up. Appearance of HGV-E2 antibody was associated with the clearance of HGV viraemia. An abnormal ALT level was noted to depend on HCV infection but not on HGV infection in both the acute and chronic phases of transfusion-associated hepatitis.
 ...
PMID:Evolution of hepatitis G virus infection and antibody response to envelope protein in patients with transfusion-associated non-A, non-B hepatitis. 965 67

We investigated the possible role of hepatitis G virus (HGV or GBV-C) in the aetiology of acute non-A-E hepatitis in Argentina by detecting viral RNA in sera by reverse transcriptase-polymerase chain reaction (RT-PCR) using primers specific for the putative NS3 helicase region of HGV. Sixty two patients with acute hepatitis were included in this study. The absence of hepatitis A-E was confirmed by serological testing, and all patients were negative for HCV RNA and autoimmune markers. All patients denied alcohol intake and the use of hepatotoxic drugs. Their mean age was 35.3 years and 37 were males. HGV RNA was present in 19/62 (30.6%) of the patients with non-A-E acute hepatitis. Among HGV-positive patients, three had parenteral risk factors within 3 months of onset, one was a health care worker, one was sexually promiscuous, one had travelled to the Middle East and 13 (68.4%) had no history of parenteral exposure. Epidemiological, clinical and biochemical features between HGV-positive and negative patients did not achieve statistical significance. Hence, HGV appears to play a role in the pathogenesis of acute viral hepatitis; however, the etiology of a significant number of hepatitis cases remains unclear, suggesting the existence of an additional agent(s). The absence of parenteral exposure in most of the HGV RNA-positive patients in this study shows that routes of community-acquired HGV infection are not yet completely understood.
 ...
PMID:Detection of hepatitis G virus RNA in patients with acute non-A-E hepatitis. 965 68

Recently, two new flaviviruses, GB virus A (GBV-A) and GB virus B (GBV-B), were identified in the plasma of a tamarin infected with the hepatitis GB agent. A third virus, GB virus C (GBV-C), was subsequently identified in humans. In the current study, representational difference analysis (RDA) was used to search for a new virus in the serum of a chimpanzee that developed acute resolving hepatitis following inoculation with a pool of chimpanzee plasma. The plasma pool originated from serial passages of a human sample containing virus-like particles. Numerous cDNA clones were obtained that exhibited 62-80% identity with GBV-C. With the exception of the extreme 5' and 3' ends, the complete viral genome was sequenced, revealing a single large open reading frame encoding a 2833 amino acid polyprotein that contains two envelope proteins, two proteases, a helicase, and an RNA-dependent RNA polymerase. Phylogenetic analysis of the new virus indicates that it is closely related to GBV-C, yet still sufficiently divergent as to be placed in a separate group, tentatively labeled GB virus Ctroglodytes (GBV-Ctro). Numerous human samples were screened by reverse transcriptase-polymerase chain reaction (RT-PCR), but GBV-Ctro sequence was not detected. However, a second chimpanzee inoculated with the same plasma pool was shown to develop a GBV-Ctro infection. Although isolated from an Old World primate with hepatitis, the primary host of GBV-Ctro and any association with disease remains to be determined.
 ...
PMID:Isolation of a GB virus-related genome from a chimpanzee. 970 Jun 32

Hepatitis G virus (HGV) is a recently discovered RNA virus, which belongs to the Flaviviridae family. Although HGV infection is usually not associated with elevated serum transaminases, some recent studies have reported that HGV infection is found in a significant number of patients with fulminant hepatitis and may play a role in its etiopathogenesis. In this study the prevalence of HGV infection was determined in 500 healthy blood donors and in 24 patients admitted to hospital because of acute liver failure caused by fulminant hepatitis. The presence of HGV RNA was tested in sera, obtained at admission and before any transfusion was given, by a sensitive seminested reverse transcriptase-polymerase chain reaction (RT-PCR) assay specific for detection of the non-structural (NS)5 region. Nine of the 500 blood donors (1.8%) and two of the 24 patients (8.3%) were found to be HGV RNA positive. One patient was co-infected with HCV and was known to be an intravenous (i.v.) drug user. After intensive supporting treatment, this patient recovered completely. The second patient had no serological markers of known viral hepatitis infection, including hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and herpes simplex virus (HSV). This patient was successfully transplanted. From both patients, from HGV RNA-positive healthy blood donors and from other patients coinfected with HCV, a part of the HGV NS3 region (nucleotides 4191-4345, EMBL entry U45966) was cloned and sequenced. Sequence comparison revealed that the NS3 region of HGV in patients with fulminant hepatitis contained three nucleotide substitutions as part of the six substitutions described in previous work. These nucleotide substitutions were not found in the tested blood donors or in patients with HCV co-infection. Our findings therefore support the concept of the association of fulminant hepatitis with infection of a specific HGV strain.
 ...
PMID:Hepatitis G virus infection in acute fulminant hepatitis: prevalence of HGV infection and sequence analysis of a specific viral strain. 979 13

Raw sewage samples from an area where hepatitis E is not endemic (Barcelona, Spain) were analyzed by reverse transcriptase-PCR followed by nested PCR. One of the 37 tested samples showed a positive result for hepatitis E virus (HEV). The detected strain was amplified by inoculation into rhesus monkeys, and the course of the infection was studied by analyzing serological and biochemical parameters and by monitoring the presence of HEV in serum and feces. Fecal suspensions from the rhesus monkeys were used as the source of viral particles for sequence analysis. Eighty percent of the genome of the isolated strain, named BCN, was sequenced and found to be phylogenetically related to Asian (Indian) strains, with a 98% nucleotide identity with an isolate from Madras, India. Since this was a single isolation we cannot conclude that HEV is regularly present in the sewage. However, the finding of viable HEV in sewage has implications for contamination of the environment and shellfish by HEV and must be considered in the diagnosis of viral hepatitis in regions of nonendemic hepatitis.
 ...
PMID:Characterization of a strain of infectious hepatitis E virus isolated from sewage in an area where hepatitis E is not endemic. 979 11

Nevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor widely used in combination with other antiretroviral agents for the treatment of human immunodeficiency virus disease. To establish its safety profile, we conducted a review of data from prospective US and international clinical trials involving a total of 906 adult patients and 468 pediatric patients treated with NVP. Drug-related adverse events were similar in adults and children, with rash and nausea most frequently reported in adults and rash and granulocytopenia most frequently reported in children. A separate analysis of rash based on data from adult patients in controlled trials demonstrated a 16% rate of NVP-attributable rash in these patients. Of patients with NVP-associated rash, 65% developed rash within the first 6 weeks of therapy, and it has been shown that a lower lead-in dose (200 mg/d vs the standard 400 mg/d) for the first 2 weeks of NVP treatment reduces the frequency of drug-associated rash. Serious rash (Stevens-Johnson syndrome [SJS] or SJS/toxic epidermal necrolysis transition syndrome) occurred with an incidence of 0.3% and clinical hepatitis with an incidence of 1.0% among NVP-treated patients in clinical trials. Adverse event data from long-term clinical trials demonstrated a lower incidence of NVP-related adverse events than in short-term trials of NVP therapy. An analysis of abnormal laboratory findings using thresholds similar to those found in the prescribing information for other commonly used antiretroviral agents and data from controlled trials in adults showed that the most frequently observed laboratory abnormalities were elevations in liver function test results. Approximately 50,000 patients in the United States had been treated with marketed NVP at the time of writing, and postmarketing surveillance has supported the overall safety profile observed in clinical trials. NVP has been shown to be well tolerated in both adult and pediatric patients.
 ...
PMID:Safety profile of nevirapine, a nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus infection. 991 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>