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Results for “viral replication”

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At least 379 records · Page 21Linked to original sources

PubMed2005

Hepatitis C virus NS5B delays cell cycle progression by inducing interferon-beta via Toll-like receptor 3 signaling pathway without replicating viral genomes.

To clarify the pathogenesis of hepatitis C virus (HCV), we have studied the effects of HCV proteins using human hepatocytes. Here, we found that HCV NS5B, an RNA-dependent RNA polymerase, delayed cell cycle progression through the S phase in PH5CH8 immortalized human hepatocyte cells. Since treatment with anti-interferon (IFN)-beta neutralizing antibody restored the cell cycle delay, IFN-beta was deemed responsible for the cell cycle delay in NS5B-expressing PH5CH8 cells. The induction of IFN-beta and the cell cycle delay were overridden by the down-regulation of Toll-like receptor 3 (TLR3) through RNA interference in NS5B-expressing PH5CH8 cells. Moreover, the NS5B full form was required for the cell cycle delay, the induction of IFN-beta, and the activation of the IFN-beta signaling pathway. Our findings revealed that NS5B induced IFN-beta through the TLR3 signaling pathway in immortalized human hepatocytes even without replicating viral genomes.

Cell Cycle↗

PubMed1994

Measurement of HBsAg to monitor hepatitis B viral replication in patients on alpha-interferon therapy.

HBsAg was measured quantitatively in serum samples collected serially before and after the HBeAg seroconversion date from 69 patients with HBeAg seroconversion and 17 patients with both HBeAg and HBsAg seroconversion. In patients with only HBeAg seroconversion the median HBsAg level decreased from 8.39 micrograms/ml (range 0.01-57.51) before HBeAg seroconversion to 3.53 micrograms/ml (range 0.002-68.66) after seroconversion (P < 0.001). No significant drop in HBsAg was found for the control group (18 HBeAg-positive patients without seroconversion). From 12 other patients on alpha-interferon therapy HBsAg was quantitatively assayed monthly during and after therapy; HBsAg levels were compared to the levels of HBV-DNA and HBeAg. We observed a good correlation between the HBsAg level and both the HBV-DNA (r = 0.76; P < 0.001) and the HBeAg (r = 0.70; P < 0.001) level, irrespective of the response to alpha-interferon. Quantified assessment of HBsAg appears promising as a simple and cheap method for monitoring viral replication in chronic hepatitis B in patients undergoing interferon therapy.

Hepatitis B↗

PubMed1991

T lymphocyte activation is associated with viral replication in chronic hepatitis B virus infection of childhood.

Activated circulating T lymphocytes expressing HLA-DR (mean +/- s.d. 11.0 +/- 5.2%) or interleukin-2 receptor (IL-2R) (2.1 +/- 1.7%) were significantly increased in 63 children with chronic hepatitis B virus (HBV) infection when compared with 33 age-matched healthy controls (3.0 +/- 1.3%, P less than 0.01, and 0.1 +/- 0.4%, P less than 0.01). HBeAg-positive patients had higher percentage of DR (11.9 +/- 5.1%) or IL-2R (2.4 +/- 1.7%) positive T lymphocytes than anti-HBe-positive children (7.4 +/- 3.6% and 1.1 +/- 1.5%, P less than 0.01 and P = 0.02 respectively). Similarly, HBV DNA-positive patients had higher percentage of DR (10.5 +/- 3.3) or IL-2R (3.2 +/- 1.7%) positive T cells than HBV DNA-negative children (6.6 +/- 2.8% and 1.2 +/- 1.5%, P less than 0.01 for both). There was a positive correlation between percentage of DR positive T lymphocytes and levels of HBV DNA. Sixty-two per cent of the DR-positive T lymphocytes were cytotoxic/suppressor and 35% helper/inducer. The relationship between viral replication and T lymphocyte activation is discussed.

Adolescent↗

PubMed1987

Induction of demyelination by a temperature-sensitive mutant of the coronavirus MHV-A59 is associated with restriction of viral replication in the brain.

The neurovirulence of eight temperature-sensitive (ts) mutants of mouse hepatitis virus strain A59 in 4-week-old BALB/c mice was investigated. Whereas a dose of 100 p.f.u. of wild-type virus killed mice within a week, a 1000-fold higher dose of ts mutants did not. Three ts mutants induced demyelinating disease in the central nervous system (CNS). The pathology of the demyelinating disease caused by one mutant, designated ts-342, was studied in detail. Pathological changes, starting 3 days post-inoculation (p.i.), were characterized by inflammation and demyelination in the CNS. Antibody responses directed against all virus-specific structural proteins were present at 7 days p.i. No virus particles were observed by electron microscopy at 14 days p.i. However, macrophages and lymphocytes were abundant in the areas of demyelination. The growth kinetics in vivo of wild-type virus, ts-342 and a revertant of ts-342 were compared. Wild-type virus and the revertant replicated rapidly in the brain and spread to the liver causing a lethal hepatitis. Ts-342, however, replicated to a much lesser extent within the brain and could not be detected in the blood or liver. The ts lesion in the genome of ts-342 seems, therefore, to determine the outcome of the infection.

Animals↗

PubMedDate not supplied

Hepatocyte hepatitis B surface antigen expression in chronic hepatitis B virus carriers in Singapore: correlation with viral replication and liver pathology.

The hepatocyte hepatitis B surface antigen (HBsAg) expression in 149 liver biopsies from 124 chronic hepatitis B virus (HBV) carriers was correlated with serum HBV DNA status and histologic activity. Hepatocyte HBsAg was stained by the peroxidase-antiperoxidase method and serum HBV DNA was determined by dot blot hybridization. Sixty-five biopsies (44%) showed minimal changes (MC), 82 biopsies (55%) showed chronic liver disease (CLD) and 2 biopsies (1%) showed hepatocellular carcinoma. Hepatocyte HBsAg was found in 144 biopsies (97%). It was present in the cytoplasm of 141 specimens (95%) and/or plasma membrane of 48 specimens (32%). Approximately half (45%) of the cytoplasmic HBsAg-positive biopsies showed discrete distribution, while the other half (55%) were grouped. Fifty-five per cent (77 of 141) of cytoplasmic HbsAg-positive biopsies had CLD, while 44% (62 of 141) showed MC. There was no relationship between the presence of cytoplasmic HBsAg or its topographic distribution with disease activity. Membrane HBsAg distribution was similar for both groups of patients (MC vs CLD: 25 of 65 (38%) vs 23 of 82 (28%); P = NS). Serum HBV DNA was detected in 98 patients (66%) and was seen mostly in association with CLD (CLD vs MC: 61% vs 39%, P less than 0.001). It was also detected more often in the sera of patients with membrane HBsAg than in those with cytoplasmic HBsAg staining (41 of 48 (85%) vs 97 of 141 (67%); P less than 0.02). However, discrete distribution of cytoplasmic HBsAg was associated with positive serum HBV DNA when compared with grouped distribution (52 of 63 (83%) vs 43 of 78 vs (55%); P less than 0.005).

Carrier State↗

PubMedDate not supplied

Spontaneous disappearance of viral replication and liver cell inflammation in HBsAg-positive chronic active hepatitis: results of a placebo vs. interferon trial.

In 20 patients with HBsAg-and HBeAg-positive chronic active hepatitis, we determined the long-term effect of human leukocyte interferon as well as placebo treatment. During the 2-year follow-up period, HBsAg remained present in all patients, but the Dane particle markers HBeAg and DNA polymerase disappeared in two of 10 patients who had received interferon, and in 4 of 10 patients from the placebo group. Patients, with loss of HBeAg initially had HBs antigenemia for a longer period as well as a lower serum concentration of both HBsAg and DNA polymerase, fewer HbcAg-containing hepatocyte nuclei, and higher serum transaminase levels than did the patients in whom HBeAg persisted. Disappearance of Dane particle markers was associated with a decrease in HBsAg titer, appearance of anti-HBe, normalization of the serum transaminases, and morphological transition to inactive chronic hepatitis. We conclude that, in HBsAg- and HBeAg-positive chronic active hepatitis, disappearance of Dane particle markers occurs in approximately 30% of the patients within a 2-year period and that arrest of active viral replication is associated with loss of activity of chronic hepatitis. Treatment with human leukocyte interferon in the doses used in this study did not change the natural course of the disease.

Adult↗

PubMed1996

Inhibition of viral replication by genetically engineered mutants of the duck hepatitis B virus core protein.

The hepatitis B virus (HBV) nucleocapsid consists of 240 viral core proteins that are arranged in a highly symmetrical structure, HBV replication can only take place inside intact nucleocapsids. In the present study, we investigated whether genetically engineered core mutants can inhibit viral replication by interfering with the formation of intact nucleocapsids. Using the duck hepatitis B virus (DHBV) model, a series of core protein mutants was generated. Polymerase chain reaction-amplified fragments from the bacterial lacZ gene expressing up to 282 amino acids were added either to the amino- or carboxy-terminus of the DHBV core protein. In addition, carboxy-terminal extensions were generated by fusing the DHBV core protein with the DHBV small surface protein or various fragments of the viral polymerase. Finally, the green fluorescent protein (GFP) was fused in-frame to the carboxy-terminus of the DHBV core protein. In this chimeric protein, GFP is still functional and can act as a reporter molecule. The various core protein mutants were tested for their potential antiviral activity by cotransfection with a replication-competent DHBV construct into the avian hepatoma cell line LMH. Carboxy-terminal, but not amino-terminal, DHBV core mutants inhibited DHBV replication by up to 90% at an effector-to-target ratio of 1:10, thus displaying a dominant negative phenotype. Antiviral activity was species-specific and caused by posttranslational interference with viral replication. The DHBV core-GFP fusion protein should be an ideal tool to assess the antiviral potential of dominant negative core proteins in vivo.

Amino Acid Sequence↗

PubMed2001

Acute adrenal infection by HSV-1: role of apoptosis in viral replication.

Replication of herpes simplex virus type 1 (HSV-1) in the adrenal gland of mice was observed 12 h after intravenous inoculation, peaked at 48 h (7 x 10(7) PFU/tissue), and was maintained until death. Virus spread to the bilateral intermediolateral column of the thoracic spinal cord. Infected cells appeared in the fascicular zone of the adrenal cortex 12 h after infection, and cell death was evident in lesions found in the adrenal cortex. Lesions involved the medulla 48 h after inoculation. In cortical lesions, cell nuclei were fragmented or shrunken with little damage to the cytoplasm. DNA fragmentation appeared 12 h after inoculation and increased mainly in cortical lesions, which were characterized by apoptosis induced by HSV-1 infection. In the adrenal medulla, cells were fused and formed multinucleated giant cells but rarely displayed cell death. Macrophages, which serve as a frontal barrier to viral infection in the adrenal gland, especially the cortex, were fewer in number than those found in the liver or spleen. It is likely that HSV-1 easily infects the adrenal gland, resulting in suppression of local immunity, and that adrenal cell apoptosis serves as a primitive type of immunity to limit viral replication.

Acute Disease↗

PubMed2000

Cytotoxicity, apoptosis, and viral replication in tumor cells treated with oncolytic ribonucleotide reductase-defective herpes simplex type 1 virus (hrR3) combined with ionizing radiation.

The viral ribonucleotide reductase (rR)-defective herpes simplex type-1 (HSV-1) virus (hrR3) has been shown previously to preferentially replicate in and kill tumor cells. This selectivity is associated with tumor cell up-regulation of mammalian rR. Ionizing radiation (IR) is currently used in the therapy of many malignancies, including glioblastoma, cervical carcinoma, and pancreatic carcinoma. IR has been shown to up-regulate mammalian rR in tumor cells and appears to increase the efficacy of at least one non-rR-deleted HSV-1 strain in an in vivo tumor model. Here, we test the hypothesis that a single therapeutic radiation fraction will increase the replication and toxicity of hrR3 for malignant cell lines in vitro. PANC-1 pancreatic carcinoma, U-87 glioblastoma, and CaSki cervical carcinoma cell lines were treated with varying doses of IR and subsequently infected with hrR3 or KOS (wild-type HSV-1 strain). Cell survival was then measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and trypan blue exclusion cytometry. At 72 hours posttreatment, irradiation with 2 Gy reduced survival from 100% to 76% in noninfected cells, from 61% to 48% in KOS-infected cells, and from 39% to 27% in hrR3-infected PANC-1 cells. As such, analysis of variance indicated that the toxicity of the two modalities was additive. Similar additivity was seen in U-87 MG and CaSki cells. Absolute survival of hrR3-infected or KOS-infected PANC-1 cells decreased as a function of time after treatment (24-72 hours) and multiplicity of infection (MOI) (0.05-5.0). However, the relative decrease in survival with the addition of IR to hrR3 or KOS in PANC-1 cells was not markedly affected by altering MOI (0.05-5.0), time (24-72 hours), radiation dose (2-20 Gy), or cell culture conditions (confluent/growth arrested). We used fluorescence-activated cell sorter analysis with the cationic lipophilic dye DiOC6 to quantify a reduction in mitochondrial membrane potential that'is associated with apoptosis. Fluorescence-activated cell sorter analysis indicated increased apoptosis in both hrR3- and IR-treated cells at 48-72 hours, with hrR3 alone producing the most induction. Viral yields from PANC-1 cells after irradiation and infection were examined. No significant differences were seen between irradiated and nonirradiated cells in viral replication, with hrR3 producing single-step titers of 3.1 +/- 0.9 x 10(5) and 4.0 +/- 1.2 x 10(5) plaque-forming units/mL in nonirradiated and irradiated cells. Thus, complementary toxicity was seen between IR and hrR3 or KOS, regardless of cell type, time, MOI, IR dose, or culture conditions, without evidence of augmented apoptosis or viral replication.

Apoptosis↗

PubMed1996

Prolonged and high dose recombinant interferon alpha-2b alone or after prednisone priming accelerates termination of active viral replication in children with chronic hepatitis B infection.

BACKGROUND: There is no generally accepted treatment for chronic hepatitis B (HB) infection in children. OBJECTIVES: To evaluate the efficacy of a prolonged course of high dose interferon alone or after prednisone priming in children with chronic HB infection. METHODS: The outcome of 31 children with HB e antigen (HBeAg)-positive chronic hepatitis who randomly received either no treatment (n = 9) or 10 million units of interferon alpha-2b/m2, alone (n = 13) or after prednisone priming (n = 9), three times weekly for 1 year was studied. RESULTS: One patient withdrew from treatment. By the end of the first year treatment induced a loss of HB virus DNA and HBeAg from serum in 10 of 21 patients (48%), and a loss of HB surface antigen (HBsAg) in 4 (19%). Alanine aminotransferase values became normal in one patient (4.8%). Response rates in the two groups of treated patients were similar. In controls only one patient lost HBeAg and HBV DNA (11%; P = 0.05), and none lost HBsAg or showed alanine aminotransferase normalization (P = 0.21 and 0.70, respectively). After a posttreatment 2-year follow-up there were still no differences in the response rates of the two treatments; of the 21 pooled treated patients, 61% lost HBeAg and DNA and 67% normalized alanine aminotransferase (vs. 33 and 44% of controls, respectively; P = 0.32 and 0.40). Reversion to HBeAg and HBV DNA negativity in treated patients occurred significantly earlier (P = 0.02 and 0.006, respectively) than in controls. No further patient lost HBsAg, but one reacquired HBsAg. Treated patients had posttreatment histologic scores better than controls (P = 0.03). CONCLUSIONS: Our medium term follow-up results indicate that a prolonged course of high dose interferon in children with chronic HB infection, regardless of prednisone priming, poorly affects response rates but significantly speeds termination of active viral replication.

Adolescent↗

PubMed2003

Membrane association of hepatitis C virus nonstructural proteins and identification of the membrane alteration that harbors the viral replication complex.

Hepatitis C virus (HCV) replicates its genome in a membrane-associated complex composed of viral proteins, replicating RNA, and altered cellular membranes. Determinants for membrane association of the HCV nonstructural proteins involved in genome replication have been defined. In addition, a specific membrane alteration, designated membranous web, was recently identified as the site of viral RNA synthesis and, therefore, represents the HCV replication complex. These findings add to our current understanding of the HCV life cycle and may ultimately allow to design novel antiviral strategies against hepatitis C.

Amino Acid Sequence↗

PubMed1998

Epstein-Barr virus small RNA (EBER) genes: differential regulation during lytic viral replication.

In every latently Epstein-Barr virus-infected cell the viral genes EBER-1 and EBER-2 are transcribed by polymerase III. In lytically infected cells in vivo the EBER genes could not be detected. However, in cell culture downregulation could not be confirmed, and hence the relevance of this shutdown to the replication of the virus was not clear. We assayed the transcriptional activity of the EBER genes by nuclear run-on assays with enriched lytically infected cells and demonstrated that EBER-1 and EBER-2 are differentially downregulated on the transcriptional level during the switch to lytic viral replication. This downregulation was an early event during the lytic replication of the virus.

Base Sequence↗

PubMed2004

Hepatitis B virus: pathogenesis, viral intermediates, and viral replication.

Although HBV has the potential to generate an almost limitless spectrum of quasispecies during chronic infection, the viability of the majority of these quasispecies is almost certainly impaired due to constraints imposed by the remarkably compact organization of the HBV genome. On the other hand, single mutations may affect more than one gene and result in complex and unpredictable effects on viral phenotype. Better understanding of the constraints imposed by gene overlap and of genotype-phenotype relationships should help in the development of improved antiviral strategies and management approaches. Although the probability of developing viral resistance is directly proportional to the intensity of selection pressure and the diversity of quasispecies, potent inhibition of HBV replication should be able to prevent development of drug resistance because mutagenesis is replication dependent. If viral replication can be suppressed for a sufficient length of time, viral load should decline to a point where the continued production of quasispecies with the potential to resist new drug treatments no longer occurs. Clinical application of this concept will require optimization of combination therapies analogous to highly active antiretroviral therapy (HAART) for HIV infection. Total cure of hepatitis B will require elimination of the intranuclear pool of viral minichromosomes, which will probably only be achieved by normal cell turnover, reactivation of host immunity, or elucidation of the antiviral mechanisms operating during cytokine clearance in acute hepatitis B (see Fig. 1).

DNA, Viral↗

PubMed2005

Structural characterization of the highly conserved 98-base sequence at the 3' end of HCV RNA genome and the complementary sequence located at the 5' end of the replicative viral strand.

Oligoribonucleotides that corresponded to the X regions of the (+) and (-) polarity strands of HCV RNA, as well as several shorter oligomers comprising defined stem-loop motifs of their predicted secondary structure models, were analyzed by Pb2+-induced cleavage, partial digestion with specific nucleases and chemical modification. Patterns characteristic of the motifs were compared with those obtained for the full-length molecules and on the basis of such 'structural fingerprinting' conclusions concerning folding of regions X were formulated. It turned out that the secondary structure model of X(+) RNA proposed earlier, the three-stem-loop model composed of hairpins SL1, SL2 and SL3, was only partially consistent with our experimental data. We confirmed the presence of SL1 and SL3 motifs and showed that the single-stranded stretch adjacent to the earlier proposed hairpin SL2 contributed to the folding of that region. It seemed to be arranged into two hairpins, which might form a hypothetical pseudoknot by changing their base-pairing systems. These data were discussed in terms of their possible biological significance. On the other hand, analysis of the X(-) RNA and its sub-fragments supported a three-stem-loop secondary structure model for this RNA.

Base Sequence↗

PubMed2004

Potent, selective and cell-mediated inhibition of human herpesvirus 6 at an early stage of viral replication by the non-nucleoside compound CMV423.

CMV423 (2-chloro-3-pyridin-3-yl-5,6,7,8-tetrahydroindolizine-1-carboxamide) is a new antiviral agent with potent and selective in vitro activity against the beta-herpesvirus human cytomegalovirus (HCMV), but not against alpha- or gamma-herpesviruses. Here we report that its activity also extends to human herpesvirus 6 (HHV-6) and 7 (HHV-7). When compared in vitro to ganciclovir and foscarnet (the standard drugs recommended for treatment of HHV-6 infections), CMV423 showed a superior selectivity, due to its high activity (antiviral IC(50): 53nM) and low cytotoxicity (CC(50): 144microM), both in continuous cell lines and in CBLCs infected with HHV-6. From mechanistic experiments at the level of viral mRNA and protein expression, we learned that CMV423 targets an event following viral entry but preceding viral DNA replication. Its antiviral action was dependent on the cell line used, implying involvement of a cellular component. When compared to a panel of known protein kinase inhibitors, CMV423 was found to share anti-HHV-6 characteristics with herbimycin A, which affects tyrosine kinase activity through heat shock protein 90 (Hsp90) inhibition. We demonstrated that high concentrations of CMV423 have an inhibitory effect on the total cellular protein tyrosine kinase activity, and that CMV423 and herbimycin A, when combined, act synergistically against HHV-6. The activities of cyclin-dependent kinases, protein kinases A and C, and the HHV-6-encoded pU69 kinase were not affected. We, therefore, conclude that CMV423 exerts its activity against HHV-6 through inhibition of a cellular process that is critical at early stages of viral replication and that may affect protein tyrosine kinase activity.

Antiviral Agents↗

PubMed2026

Japanese encephalitis virus hijacks the host purine biosynthetic network to promote viral replication in neurons.

Japanese encephalitis virus (JEV) is an important neurotropic orthoflavivirus that poses a threat to both human and animal health. However, the mechanism underlying its rapid replication in the central nervous system (CNS) remains poorly understood. In this study, we conducted metabolomic profiling of JEV-infected mouse brains and neurons, revealing a profound reprogramming of central carbon metabolism, particularly an enhancement in nucleotide synthesis. Integrated multi-omics analyses confirmed that JEV infection transcriptionally upregulates key enzymes involved in de novo purine biosynthesis (DNPB), one-carbon (1C) metabolism, and the pentose phosphate pathway (PPP) in neurons. Pharmacological inhibition of the core DNPB enzymes potently suppressed JEV replication in neurons and reduced both viral loads and neuroinflammation in JEV-infected mice, suggesting the essential role of DNPB in JEV replication within CNS. Mechanistically, we delineated the critical functions of both the non-oxidative PPP and MTHFD2-mediated 1C metabolism, which jointly supply essential precursors, such as ribose-5-phosphate and formyl groups, for the de novo biosynthesis of purines required for viral RNA replication. These findings unveil a strategy by which JEV co-opts the host's purine biosynthetic machinery to fulfill the nucleotide demands for its genomic replication, establishing DNPB and its supporting pathways as promising therapeutic targets for infections caused by JEV and other neurotropic viruses.

Animals↗

PubMed1987

A recombinant plasmid from which an infectious adeno-associated virus genome can be excised in vitro and its use to study viral replication.

A recombinant plasmid carrying an infectious adeno-associated viral genome was constructed that differs in several key respects from previously described recombinants. First, the vector is pEMBL8(+), which allows isolation of viral plus and minus strands. Second, the inserted viral sequences contain two XbaI cleavage sites that flank the viral coding domain. These inserts do not affect replication of the virus, and they allow nonviral sequences to be easily inserted between the cis-acting terminal repeats of adeno-associated virus. Third, the viral genome is flanked by PvuII cleavage sites that allow the entire, infectious viral chromosome to be excised from plasmid sequences in vitro. Viral DNA was replicated more efficiently within adenovirus-infected 293 cells if it was excised from the vector with PvuII before transfection. Presumably, the increased efficiency reflects bypass of the excision step which must normally precede replication when a recombinant plasmid enters the nucleus. The ability to bypass the excision step was exploited to search for a viral function required specifically for excision of the viral genome from the integrated state. None of the mutants tested identified a gene product required for excision that was not also essential for replication. The ability to produce pure populations of viral plus and minus strands was used to demonstrate that both strands are infectious.

Cell Line↗

PubMed1993

Delayed clearance of HBV-DNA detected by PCR in the absence of viral replication.

The polymerase chain reaction (PCR) was used to study the in vivo persistence and clearance of HBV-DNA in the serum of a monkey (Macaca mulatta) known to be naturally resistant to the HBV infection. Total infectious plasma, virus pellet, and viral DNA were inoculated into 3 different monkeys. Degradation of infectious particles and clearance of HBV-DNA were analyzed by detecting HBV-DNA sequences in serial dilutions of serum by dot blot hybridization and PCR. Semi-quantitation was carried out by comparison with minimal positive dilutions of known HBV-DNA. The presence of hepatitis B surface antigen (HB-sAg) and hepatitis B e antigen (HBeAg) in serum was also investigated. PCR assays were found positive in serial samples of the 3 monkeys, and passively transmitted viral DNA remained detectable for 3 months after inoculation. HBsAg and HBeAg were detectable for 3 weeks and 2 weeks, respectively, in a monkey inoculated with total infectious plasma. Semi-quantitation of HBV viremia showed that the amount of virus detected 1 day after injection was markedly decreased and persisted at a low level, showing a rapid and important sequestration of viral particles. Since replication can be excluded in these monkeys, the data show that HBV-DNA sequences can remain detectable at a low level in the serum for long periods. It is thus conceivable that PCR may also detect the HBV genome, eventually degraded in vivo, and a weakly positive result does not always mean ongoing viral replication.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗