SEARCH · PubMed Health

Results for “viral replication”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources

PubMed1997

Effects of mutations in the Exo III motif of the herpes simplex virus DNA polymerase gene on enzyme activities, viral replication, and replication fidelity.

The herpes simplex virus DNA polymerase catalytic subunit, which has intrinsic polymerase and 3'-5' exonuclease activities, contains sequence motifs that are homologous to those important for 3'-5' exonuclease activity in other polymerases. The role of one such motif, Exo III, was examined in this study. Mutated polymerases containing either a single tyrosine-to-histidine change at residue 577 or this change plus an aspartic acid-to-alanine at residue 581 in the Exo III motif exhibited defective or undetectable exonuclease activity, respectively, yet retained substantial polymerase activity. Despite the defects in exonuclease activity, the mutant polymerases were able to support viral replication in transient complementation assays, albeit inefficiently. Viruses replicated via the action of these mutant polymerases exhibited substantially increased frequencies of mutants resistant to ganciclovir. Furthermore, when the Exo III mutations were incorporated into the viral genome, the resulting mutant viruses displayed only modestly defect in replication in Vero cells and exhibited substantially increased mutation frequencies. The results suggest that herpes simplex virus can replicate despite severely impaired exonuclease activity and that the 3'-5' exonuclease contributes substantially to the fidelity of viral DNA replication.

Amino Acid Sequence↗

PubMed2004

RNA recombination in vivo in the absence of viral replication.

To study fundamental aspects of RNA recombination, an in vivo RNA recombination system was established. This system allowed the efficient generation of recombinant cytopathogenic pestiviruses after transfection of synthetic, nonreplicatable, subgenomic transcripts in cells infected with a replicating noncytopathogenic virus. Studies addressing the interplay between RNA recombination and replication revealed that cotransfection of noninfected cells with various pairs of nonreplicatable RNA derivatives also led to the emergence of recombinant viral genomes. Remarkably, homologous and nonhomologous recombination occurred between two overlapping transcripts, each lacking different essential parts of the viral RNA-dependent RNA polymerase (RdRp) gene. Apart from the generally accepted viral replicative copy choice recombination, our results prove the existence of a viral RdRp-independent mechanism of RNA recombination that occurs in vivo. It appears likely that such a mechanism not only contributes to the evolution of RNA viruses but also leads to the generation of recombinant cellular RNAs.

Amino Acid Sequence↗

PubMed2005

Human serum facilitates hepatitis C virus infection, and neutralizing responses inversely correlate with viral replication kinetics at the acute phase of hepatitis C virus infection.

The factors leading to spontaneous clearance of hepatitis C virus (HCV) or to viral persistence are elusive. Understanding virus-host interactions that enable acute HCV clearance is key to the development of more effective therapeutic and prophylactic strategies. Here, using a sensitive neutralization assay based on infectious HCV pseudoparticles (HCVpp), we have studied the kinetics of humoral responses in a cohort of acute-phase patients infected during a single nosocomial outbreak in a hemodialysis center. The 17 patients were monitored for the spontaneous outcome of HCV infection for 6 months before a treatment decision was made. Blood samples were taken frequently (15 +/- 4 per patient). Phylogenetic analysis of the predominant virus(es) revealed infection by only one of two genotype 1b strains. While all patients seroconverted, their sera induced two opposing effects in HCVpp infection assays: inhibition and facilitation. Furthermore, the ability of sera to facilitate or inhibit infection correlated with the presence of either infecting HCV strain and divided the patients into two groups. In group 1, the progressive emergence of a relatively strong neutralizing response correlated with a fluctuating decrease in high initial viremia, leading to control of viral replication. Patients in group 2 failed to reduce viremia within the acute phase, and no neutralizing responses were detected despite seroconversion. Strikingly, sera of group 2, as well as naive sera, facilitated infection by HCVpp displaying HCV glycoproteins from different genotypes and strains, including those retrieved from patients. These results provide new insights into the mechanisms of viral persistence and immune control of viremia.

Acute Disease↗

PubMed1996

Human cytomegalovirus uracil DNA glycosylase is required for the normal temporal regulation of both DNA synthesis and viral replication.

Human cytomegalovirus (CMV) encodes a gene, UL114, whose product is homologous to the uracil DNA glycosylase and is highly conserved in all herpesviruses. This DNA repair enzyme excises uracil residues in DNA that result from the misincorporation of dUTP or spontaneous deamination of cytosine. We constructed a recombinant virus, RC2620, that contains a large deletion in the UL114 open reading frame and carries a 1.2-kb insert containing the Escherichia coli gpt gene. RC2620 retains the capacity to replicate in primary human fibroblasts and reaches titers that are similar to those produced by the parent virus but exhibits a significantly longer replication cycle. Although the rate of expression of alpha and beta gene products appears to be unaffected by the mutation, DNA synthesis fails to proceed normally. Once initiated, DNA synthesis in mutant virus-infected cells proceeds at the same rate as with wild-type virus, but initiation is delayed by 48 h. The mutant virus also exhibits two predicted phenotypes: (i) hypersensitivity to the nucleoside analog 5-bromodeoxyuridine and (ii) retention of more uracil residues in genomic DNA than the parental virus. Together, these data suggest UL114 is required for the proper excision of uracil residues from viral DNA but in addition plays some role in establishing the correct temporal progression of DNA synthesis and viral replication. Although such involvement has not been previously observed in herpesviruses, a requirement for uracil DNA glycosylase in DNA replication has been observed in poxviruses.

Base Sequence↗

PubMed1998

Human thymidine kinase can functionally replace herpes simplex virus type 1 thymidine kinase for viral replication in mouse sensory ganglia and reactivation from latency upon explant.

Herpes simplex virus type 1 thymidine kinase exhibits a strikingly broad substrate specificity. It is capable of phosphorylating deoxythymidine and deoxyuridine as does human thymidine kinase, deoxycytidine as does human deoxycytidine kinase, the cytosolic kinase whose amino acid sequence it most closely resembles, and thymidylate as does human thymidylate kinase. Following peripheral inoculation of mice, viral thymidine kinase is ordinarily required for viral replication in ganglia and for reactivation from latency following ganglionic explant. To determine which activity of the viral kinase is important for replication and reactivation in mouse ganglia, recombinant viruses lacking viral thymidine kinase but expressing individual human kinases were constructed. Each recombinant virus expressed the appropriate kinase activity with early kinetics following infection of cultured cells. The virus expressing human thymidine kinase exhibited thymidine phosphorylation activity equivalent to approximately 5% of that of wild-type virus in a quantitative plaque autoradiography assay. Nevertheless, it was competent for ganglionic replication and reactivation following corneal inoculation of mice. The virus expressing human thymidylate kinase was partially competent for these activities despite failing to express detectable thymidine kinase activity. The virus expressing human deoxycytidine kinase failed to replicate acutely in neurons or to reactivate from latency. Therefore, it appears that low levels of thymidine phosphorylation suffice to fulfill the role of the viral enzyme in ganglia and that this role can be partially fulfilled by thymidylate kinase activity alone.

Animals↗

PubMed1988

In vitro Sendai viral replication in pulmonary macrophages from mice treated with 4-ipomeanol.

The ability of pulmonary macrophages from female mice given 4-ipomeanol (4-IP) to support viral replication in vitro was examined. On posttreatment days 5, 7, and 9, greater numbers of macrophages were recovered in lavage fluid from lungs of mice given 4-IP, compared with those from controls. Pulmonary macrophages recovered in lavage fluid from control mice and from mice given 4-IP supported Sendai virus replication in vitro, and nearly all Sendai virus produced in pulmonary macrophages from both groups was in an infectious form. On posttreatment days 5 and 7, slightly greater absolute numbers of virions were produced in pulmonary macrophages recovered from mice given 4-IP.

Animals↗

PubMed2005

E1A-CR3 interaction-dependent and -independent functions of mSur2 in viral replication of early region 1A mutants of mouse adenovirus type 1.

mSur2, a subunit of the Mediator complex, is required for efficient mouse adenovirus type 1 (MAV-1) replication (L. Fang, J. L. Stevens, A. J. Berk, and K. R. Spindler, J. Virol. 78:12888-12900, 2004). We examined the contributions of early-region 1A (E1A) to mSur2 function in MAV-1 replication with E1A mutant viruses. At a multiplicity of infection (MOI) of 1, viruses containing CR3 replicated better in Sur2+/+ mouse embryonic fibroblasts (MEFs) than in Sur2-/- MEFs. In contrast, viruses lacking CR3 replicated no better in Sur2+/+ than in Sur2-/- MEFs. This result supports the hypothesis that the E1A CR3-mSur2 interaction is important for MAV-1 replication. However, at an MOI of 0.05, viruses lacking CR3 showed replication defects in Sur2-/- MEFs compared to Sur2+/+ MEFs, suggesting an E1A CR3 interaction-independent function of mSur2 in MAV-1 replication in cell culture. Paradoxically, CR1Delta, CR2Delta, and CR3Delta mutant viruses replicated slightly more efficiently than wild-type (wt) MAV-1 and E1A null mutant viruses in Sur2-/- MEFs at an MOI of 0.05. Coinfection of Sur2-/- MEFs with wt MAV-1 and CR1Delta, CR2Delta, or CR3Delta mutant viruses rescued the defects of wt MAV-1 replication. This result suggests that an inhibiting effect on wt E1A protein expression and/or E1A function might account for the severe viral replication defect of MAV-1 in Sur2-/- MEFs at an MOI of 0.05. Moreover, titrations of virus yields from infected brains of inbred strains of mice showed that E1A null and CR3Delta mutant viruses had a significant defect in virus replication compared to wt MAV-1. This result supports the hypothesis that the MAV-1 E1A-mSur2 interaction is important in MAV-1 replication in mice.

ATP-Binding Cassette Transporters↗

PubMed2004

[Changes in CD4+ and CD8+ T-cell subsets in HIV-infected children differently correlate with viral replication and thymic function].

BACKGROUND AND OBJECTIVE: We intended to study the relationship between T-cell subsets with plasmatic detectable viral load (VL) and T-receptor excision circles (TREC). PATIENTS AND METHOD: Twenty HIV-infected children on highly active antiretroviral therapy (HAART) were recruited in a 1-year longitudinal retrospective study. We analyzed the relationship between changes in peripheral blood T-cell subsets, VL and TREC markers by lineal regression. RESULTS: Memory and activated CD4+ T-cells increases had a negative association with log10 TRECs increases. However, naive CD4+ T-cells increases had a positive association with log10 TRECs increases. In contrast, memory, activated and effector CD8+ T-cells increases positively correlated with log10 VL increases. On the other hand, naive CD8+ T-cells increases had a negative association with log10 VL increases. CONCLUSIONS: CD4+ and CD8+ T-cells subsets change in a different way as a response to the changes produced by HAART in HIV vertically infected children. CD4+ T-cells are more dependent on thymic function and CD8+ T-cells are more dependent on viral replication. Thus, the decline in cellular activation would allow the production of more naive T-cells by the thymus.

Antiretroviral Therapy, Highly Active↗

PubMed1996

The HNF1/HNF4-dependent We2 element of woodchuck hepatitis virus controls viral replication and can activate the N-myc2 promoter.

Transcriptional activation of myc family proto-oncogenes through the insertion of viral sequences is the predominant mechanism by which woodchuck hepatitis virus (WHV) induces liver tumors in chronically infected animals. The main target is N-myc2, a functional retroposon of the N-myc gene, but c-myc and N-myc are also marginally involved. Here we identify a major, liver-specific regulatory element in the WHV genome (We2) which efficiently activates the N-myc2 promoter in cultured hepatoma cells. In the context of the episomal viral genome, We2 governs the production of pregenomic RNA and thus plays a central role in the control of viral replication. We2 activity is primarily controlled by the liver-enriched HNF1 and HNF4 transcription factors, although NF1 and Oct proteins were also shown to bind in a central region. The expression of HNF1 and HNF4 appears to be maintained in woodchuck tumors. Thus, We2 is a prime candidate for controlling myc gene cis activation during WHV-induced hepatocarcinogenesis.

Animals↗

PubMed1995

Membrane staining for hepatitis B surface antigen on hepatocytes: a sensitive and specific marker of active viral replication in hepatitis B.

AIMS--To test the hypothesis that membranous staining of hepatitis B surface antigen (HBsAg) on the hepatocyte is a marker of active viral replication in chronic hepatitis B virus (HBV) infection. METHODS--Intrahepatic expression of HBsAg and hepatitis B core antigen (HBcAg) was studied by indirect immunofluorescence on frozen sections of liver specimens from 75 patients with chronic hepatitis B, and the results were correlated with serum levels of HBV-DNA assayed by spot hybridisation. RESULTS--Hepatocyte HBcAg was detected in all of 20 patients with serum levels of HBV-DNA > 1000 pg/ml, 18 (75%) of 24 patients with levels of HBV-DNA < or = 1000 pg/ml, and two (6.5%) of 31 patients without detectable serum HBV-DNA. The concordance between hepatocyte HBcAg and serum HBV-DNA was 89.3% (67/75). There were six patients (8%) who had detectable serum HBV-DNA but without hepatocyte HBcAg, and two patients (2.7%) who had detectable hepatocyte HBcAg but without serum HBV-DNA. Membranous staining of HBsAg associated with variable degrees of cytoplasmic HBsAg was found in all but one of 44 patients with serum HBV-DNA, irrespective of the levels, but in none of the 31 patients without serum HBV-DNA. Of the latter, HBsAg was distributed solely in the cytoplasm. In addition, there is an inverse correlation between serum levels of HBV-DNA and the degrees of cytoplasmic staining of HBsAg. The concordance between membranous staining fo HBsAg and serum HBV-DNA was 98.7% (74/75), significantly higher than that between hepatocyte HBcAG and serum HBV-DNA. CONCLUSIONS--Membranous staining of HBsAg on the hepatocyte correlated excellently with serum HBV-DNA and thus can be recognised as a sensitive and specific marker of active hepatitis B virus replication.

Adult↗

PubMed2001

Epstein-Barr virus immediate-early protein BRLF1 induces the lytic form of viral replication through a mechanism involving phosphatidylinositol-3 kinase activation.

Expression of the Epstein-Barr virus (EBV) immediate-early (IE) protein BRLF1 induces the lytic form of viral replication in most EBV-positive cell lines. BRLF1 is a transcriptional activator that binds directly to a GC-rich motif present in some EBV lytic gene promoters. However, BRLF1 activates transcription of the other IE protein, BZLF1, through an indirect mechanism which we previously showed to require activation of the stress mitogen-activated protein kinases. Here we demonstrate that BRLF1 activates phosphatidylinositol-3 (PI3) kinase signaling in host cells. We show that the specific PI3 kinase inhibitor, LY294002, completely abrogates the ability of a BRLF1 adenovirus vector to induce the lytic form of EBV infection, while not affecting lytic infection induced by a BZLF1 adenovirus vector. Furthermore, we demonstrate that the requirement for PI3 kinase activation in BRLF1-induced transcriptional activation is promoter dependent. BRLF1 activation of the SM early promoter (which occurs through a direct binding mechanism) does not require PI3 kinase activation, whereas activation of the IE BZLF1 and early BMRF1 promoters requires PI3 kinase activation. Thus, there are clearly two separate mechanisms by which BRLF1 induces transcriptional activation.

DNA-Binding Proteins↗

PubMed2002

Development of a vaccine against murine cytomegalovirus (MCMV), consisting of plasmid DNA and formalin-inactivated MCMV, that provides long-term, complete protection against viral replication.

We previously demonstrated that immunization of mice with plasmid DNAs (pDNAs) expressing the murine cytomegalovirus (MCMV) genes IE1-pp89 and M84 provided synergistic protection against sublethal viral challenge, while immunization with plasmids expressing putative virion proteins provided no or inconsistent protection. In this report, we sought to augment protection by increasing the breadth of the immune response. We identified another MCMV gene (m04 encoding gp34) that provided strong and consistent protection against viral replication in the spleen. We also found that immunization with a DNA pool containing 10 MCMV genes that individually were nonprotective elicited reproducible protection against low to intermediate doses of challenge virus. Moreover, inclusion of these plasmids into a mixture with gp34, pp89, and M84 DNAs provided even greater protection than did coimmunization with pp89 and M84. The highest level of protection was achieved by immunization of mice with the pool of 13 pDNAs, followed by formalin-inactivated MCMV (FI-MCMV). Immunization with FI-MCMV elicited neutralizing antibodies against salivary gland-derived MCMV, and of greatest importance, mice immunized with both the combined pDNA pool and FI-MCMV had undetectable levels of virus in the spleen and salivary glands after challenge. Intracellular cytokine staining of splenocytes from pDNA- and FI-MCMV-immunized mice showed that pDNA immunization elicited high levels of pp89- and M83-specific CD8(+) T cells, whereas both pDNA and FI-MCMV immunizations generated strong CD8(+)-T-cell responses against virion-associated antigens. Taken together, these results show that immunization with pDNA and inactivated virus provides strong antibody and cell-mediated immunity against CMV infection.

Amino Acid Sequence↗

PubMed2004

Intracellular expression of antisense RNA transcripts complementary to the human immunodeficiency virus type-1 vif gene inhibits viral replication in infected T-lymphoblastoid cells.

The human immunodeficiency virus type-1 (HIV-1)-encoded vif protein is essential for viral replication, virion production, and pathogenicity. HIV-1 vif interacts with the endogenous human APOBEC3G protein (an mRNA editor) in target cells to prevent its virions from encapsidation. Although some studies have established targets within the HIV-1 vif gene that are important for its biologic function, it is however important to further screen for effective therapeutic targets in the vif gene that could interfere with the HIV-1 vif-dependent infectivity and pathogenicity. This report demonstrates that HIV-1 vif antisense RNA fragments constructed within mid-3' region, notably the region spanning nucleic acid positions 5561-5705 (M-3'-AS), significantly inhibited HIV-1 replication in MT-4 and H9-infected cells and reduced the HIV-1 vif mRNA transcripts. These data clearly suggest that the above vif fragment, which corresponds to amino acid residues 96-144, could be an effective novel therapeutic target site for gene therapy applications, for the control and management of HIV-1 infection, due to its strong inhibition of HIV-1 replication in cells.

Base Sequence↗

PubMed2004

Herpes simplex virus 1 U(L)31 and U(L)34 gene products promote the late maturation of viral replication compartments to the nuclear periphery.

Herpes simplex virus 1 (HSV-1) forms replication compartments (RCs), domains in which viral DNA replication, late-gene transcription, and encapsidation take place, in the host cell nucleus. The formation of these domains leads to compression and marginalization of host cell chromatin, which forms a dense layer surrounding the viral RCs and constitutes a potential barrier to viral nuclear egress or primary envelopment at the inner nuclear membrane. Surrounding the chromatin layer is the nuclear lamina, a further host cell barrier to egress. In this study, we describe an additional phase in RC maturation that involves disruption of the host chromatin and nuclear lamina so that the RC can approach the nuclear envelope. During this phase, the structure of the chromatin layer is altered so that it no longer forms a continuous layer around the RCs but instead is fragmented, forming islands between which RCs extend to reach the nuclear periphery. Coincident with these changes, the nuclear lamina components lamin A/C and lamin-associated protein 2 appear to be redistributed via a mechanism involving the U(L)31 and U(L)34 gene products. Viruses in which the U(L)31 or U(L)34 gene has been deleted are unable to undergo this phase of chromatin reorganization and lamina alterations and instead form RCs which are bounded by an intact host cell chromatin layer and nuclear lamina. We postulate that these defects in chromatin restructuring and lamina reorganization explain the previously documented growth defects of these mutant viruses.

Animals↗

PubMedDate not supplied

Control of viral replication and disease onset in cynomolgus monkeys by HIV-1 TAT vaccine.

The Tat protein of HIV is produced early after infection and it is essential for viral replication and transmission. Tat is released by infected lymphocytes and is detected in the serum of HIV-infected patients. Extracellular Tat enters cells, where promotes HIV replication. Several studies suggest that humoral and cellular anti-Tat immunity have a protective role and may control disease progression. Of importance, Tat is conserved in its immunogenic regions among all viral subtypes except O subtype. Thus, the immunization with Tat cannot block virus entry but might block HIV replication and progression to disease. To test this hypothesis, monkeys (Macaca fascicularis) were immunized with a biologically active Tat protein. Tat was non toxic and induced specific humoral and cellular immune responses. High titers of anti-Tat antibodies capable of neutralizing Tat activity and the in vitro infection with the SHIV89.6P, Tat-specific proliferation, CTLs, TNFalpha production and skin tests were detected in the vaccinated monkeys. Most importantly, upon challenge with the highly pathogenic SHIV89.6P (10 MID50, i.v.), 5/7 of the vaccinated monkeys showed no signs of infection nor CD4+-T cell decline over a 19 months of follow-up, whereas 3/3 controls were highly infected. Thus, a Tat-vaccine is capable of controlling the acute phase of infection in nonhuman primates. These data open new avenues for the development of an AIDS vaccine.

AIDS Vaccines↗

PubMed1993

Effects of temperature on fecundity and viral replication in Amblyomma cajennense (Arachnida: Ixodidae) infected with Venezuelan equine encephalomyelitis virus.

To assess how temperature affects fecundity and Venezuelan equine encephalomyelitis (VEE) viral replication in VEE-infected Amblyomma cajennense (F.), adult ticks were inoculated intracoelomically with either VEE virus (I-A variant) or diluent. Ticks were held at 19, 26, or 33 degrees C and tested for VEE virus over 20 d. Up to 10 pairs of ticks (1 female:1 male) from each temperature group were allowed to feed on guinea pigs on day 8 after inoculation. Maximum titers did not differ significantly among infected ticks held at 19, 26, or 330 degrees C (P = 0.59), and ticks maintained high viral titers throughout the sampling period. Likewise, there was no significant difference in the number of eggs oviposited between ticks inoculated with virus or diluent and held at the same temperature, or among groups held at different temperatures (P = 0.48). The percentage of viable eggs from virus-inoculated or diluent-inoculated adults also was not significantly different (P > or = 0.14).

Animals↗

PubMed2001

HCV-RNA positivity in peripheral blood mononuclear cells of patients with chronic HCV infection: does it really mean viral replication?

AIM: To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC) and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication. METHODS: HCV-RNA was monitored in serum and PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-alpha therapy using a nested RT/PCR technique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma. RESULTS: In the IFN-alpha responding patients,HCV-RNA disappeared first from total RNA preparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNA reappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNA concentration in serum was performed before and after transition from detectable to non detectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMC preparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMC from healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration dependent PCR positivity for HCV-RNA in reisolated PBMC. CONCLUSION: The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMC preparations of chronically infected patients.

Adult↗

PubMed1995

IgM anti-hepatitis C virus in patients with chronic non-A, non-B hepatitis and their relationship to viral replication.

Patients with hepatitis C virus (HCV) infection may have different patterns of antibody response to various structural and non-structural viral antigens. We have correlated the serological patterns to the clinical features of chronic infection and to viral replication in 68 HCV-Ab-positive patients with chronic liver disease at different stages (19 with cirrhosis-hepatocellular carcinoma, 38 with chronic active hepatitis and 11 with chronic persistent hepatitis). Serum samples from each patient were assayed for HCV-IgM by enzyme immunoassay and for HCV-RNA by the polymerase chain reaction using primer sets derived from the 5'-non-coding region. The prevalence of HCV-IgM was high (54 patients (79.4%)) and the study showed a good correlation between high values of anti-HCV-IgM and the presence of HCV-RNA in serum, since HCV-RNA was detected in 35 of the 54 IgM-positive patients (64.8%) and notably in 19 of the 20 subjects with high levels of specific IgM. Conversely, all the 35 sera containing HCV-RNA were also reactive for HCV-IgM, while none of the HCV-IgM-negative sera was HCV-RNA reactive. Positivity rates for both HCV-RNA and IgM anti-HCV were higher in the more advanced stages of disease; thus, the clinical pattern of HCV chronic hepatitis seems to be strictly related to the serological pattern and the presence of HCV-RNA.

Journal Article↗