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Biomedical subjects

A Sönnerborg

Publications and source records attributed to A Sönnerborg.

At least 73 records · Page 4Linked to original sources
PubMed1998

Human and murine antibody recognition is focused on the ATPase/helicase, but not the protease domain of the hepatitis C virus nonstructural 3 protein.

The hepatitis C virus (HCV) nonstructural (NS) 3 protein has been shown to possess at least two enzymatic domains. The amino terminal third contains a serine-protease domain, whereas the carboxy terminal two thirds is comprised of an adenosine triphosphatase (ATPase)/helicase domain. These domains are essential for the maturation of the carboxy-terminal portion of the HCV polyprotein and catalyze the cap synthesis of the RNA genome. In this report, human and murine antibody responses induced by NS3 were characterized using a recombinant full-length NS3 (NS3-FL) protein, or the isolated protease or ATPase/ helicase domains, expressed and purified from Escherichia coli. Sera from 40 patients with chronic HCV infection were assayed in enzyme-linked immunoassays (EIAs) for antibody binding to the panel of NS3 proteins. Virtually all patient sera contained antibodies specific for NS3-FL and the ATPase/helicase domain, whereas only 10% of sera reacted with the protease domain of NS3. Human antibodies reactive with NS3-FL were highly restricted to the immunoglobulin G1 (IgG1) isotype and were inhibited by soluble ATPase/helicase, but not by the protease domain. The anti-NS3 (ATPase/helicase) reactivity decreased on denaturation by sodium dodecyl sulfate (SDS) and beta-mercaptoethanol (2ME), suggesting the recognition of nonlinear or conformational B-cell determinants. Similar to infected humans, mice immunized with NS3-FL developed high-titered primary antibody responses to the NS3 ATPase/ helicase domain, whereas an anti-NS3 protease response was not observed after primary or secondary immunizations. Thus, the human and murine humoral immune responses to the HCV NS3 protein are focused on the ATPase/helicase domain, are restricted to the IgG1 isotype in humans, and are conformationally dependent. Unexpectedly, in both species, the NS3 protease domain, present in the context of the full-length NS3, appears to possess low intrinsic immunogenicity in terms of antibody production.

Adenosine Triphosphatases↗
PubMed1998

Detection of hepatitis G virus/GB virus C after allogeneic bone marrow transplantation.

Abnormal liver function before allogeneic BMT has been associated with VOD. Hepatitis G virus/GB virus C (HGV) is a recently discovered virus suggested to be a cause of non-A, non-B, non-C, non-D and non-E hepatitis. The aim of this retrospective study was to analyze the risk for liver complications and time to engraftment in patients infected with HGV. Fifty patients transplanted in 1995 were examined with RT-PCR for HGV on samples collected before, and between 3 and 6 months after BMT. Seven patients had HGV detected before BMT. No patient became infected during or early after the BMT. There were no differences in either pre- or post-transplant liver function abnormalities, VOD, or time to neutrophil engraftment in patients who did or did not have HGV detected before BMT. We conclude that the importance of HGV infection for the development of post-transplant complications is limited.

Adolescent↗
PubMed1998

Comparison of 3 quantitative HCV RNA assays--accuracy of baseline viral load to predict treatment outcome in chronic hepatitis C.

The correlation between 3 assays for hepatitis C virus (HCV) RNA quantification and their respective accuracy in predicting the response to interferon and interferon/ribavirin therapy was evaluated by analysing pre-treatment sera from 100 patients. A total of 97%, 100%, and 98% of the patients tested positive by the branched DNA 2.0 assay (Quantiplex), a multi-cycle reversed transcriptase polymerase chain reaction quantitative assay (Superquant) and the Roche Amplicor Monitor assay, respectively. The correlations between the assays, in all patients and in the major genotypes 1, 2, and 3, were significant, although the levels detected by the Amplicor Monitor assay were more than 1 log lower than by the other assays. Sustained virological responders to interferon therapy, but not to combination therapy, had lower baseline viral levels than long-term non-responders (p = 0.002 by Quantiplex 2.0; p = 0.008 by Superquant; p = 0.06 by Roche Amplicor Monitor). Pre-treatment viral load greater than 3 x 10(6) Eq or copies/ml by the Quantiplex 2.0 and Superquant assays and greater than 100,000 copies/ml by the Amplicor Monitor assay predicted long-term non-response in 94%, 93% and 91% of the interferon treated patients, respectively. In conclusion, acceptable correlations between available commercial quantitative assays were found. High baseline viral load predicted long-term non-response to interferon monotherapy, whereas it did not to interferon/ribavirin combination therapy.

Antiviral Agents↗
PubMed1998

Low relative frequencies of CD26(+) CD4(+) cells in long-term nonprogressing human immunodeficiency virus type 1-infected subjects.

A broad antibody panel was used for immunophenotyping of human immunodeficiency virus type 1 (HIV-1)-infected patients who were long-term nonprogressors (LTNP). The LTNP were compared with patients in the early phase of infection and patients who had progressed to advanced immunodeficiency. Changes in CD8(+) subset distribution were observed mainly at acquisition of HIV-1 infection, whereas CD4(+) subset changes appeared during progression of HIV-1 infection. The decreasing levels of CD4(+) cells were characterized by an increasing frequency of cells expressing the activation markers HLA-Dr and CD45RO but not the CD28 surface antigen. The LTNP exhibited significant changes compared to HIV-negative patients in almost all markers. Compared to patients in the early phase of infection, the only difference was a relatively lower frequency of CD4(+) cells expressing CD26 among the LTNP. The results show that HIV-1-infected persons who have no signs of immunodeficiency despite many years of infection have an immunophenotypic pattern that is substantially different from that of noninfected persons. Despite the long duration of infection, the LTNP exhibit a pattern similar to that of newly infected persons, with the exception of lower expression of CD26 on CD4(+) cells.

Adult↗
PubMed1998

Detection of hepatitis G virus RNA in persons with and without known risk factors for blood-borne viral infections in Sweden and Honduras.

We analyzed 224 and 163 serum samples from individuals in Sweden and Honduras, respectively, for the presence of the hepatitis G virus (HGV or GB virus-C) RNA. HGV infection in both Sweden and Honduras was related to common risk factors for blood-borne infections, despite a surprisingly high frequency in groups without known risk factors.

Base Sequence↗
PubMed1998

Cooperative oligonucleotides mediating direct capture of hepatitis C virus RNA from serum.

A novel method for direct capture of hepatitis C virus (HCV) RNA from clinical samples has been developed. This approach takes advantage of the cooperative interactions between adjacently hybridized oligonucleotides. Here, this cooperative effect was combined with solid-phase technology, whereby a capture probe was covalently coupled to magnetic beads and a second probe, which anneals adjacent to the capture probe site, was prehybridized in solution to the target. When these contiguously hybridized probes were used for the extraction of HCV RNA from clinical samples, the capture efficiency was increased up to 25-fold in comparison to capture with a single probe. The applicability of this sample preparation assay was further investigated by performing a comparative study with both a conventional guanidinium extraction method and a commercial quantitative assay.

Biosensing Techniques↗
PubMed1997

Apoptosis of CD4+ and CD19+ cells during human immunodeficiency virus type 1 infection--correlation with clinical progression, viral load, and loss of humoral immunity.

Enhanced rates of programmed cell death (apoptosis) have been detected in T cells and B cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals. To evaluate the possible relevance of this event to HIV pathogenesis and disease progression, apoptosis in CD4+ T lymphocytes and CD19+ B lymphocytes, viral load, and neutralizing antibody titers were assayed in HIV-1-infected slow progressors and progressors. A correlation was found between progressive disease and apoptosis of CD4+ T cells. The extent of apoptosis in CD4+ cells was similar in slow progressors and seronegative control subjects. By contrast, we found elevated levels of B-cell apoptosis in all HIV-1-infected individuals compared with seronegative control subjects, with a tendency toward increased levels of apoptosis with progressive disease. Apoptosis in CD4+ T cells and CD19+ B cells correlated with viral RNA levels in plasma. Furthermore, higher rates of B-cell apoptosis were observed in individuals with poor neutralizing activity against a panel of six clinical HIV-1 isolates. From these results we conclude that the extent of apoptosis in cultured CD4+ cells and CD19+ cells appears to parallel the decline in CD4 cell counts in infected individuals. The finding of a relation between apoptosis in B cells and poor neutralizing capacity suggests that apoptosis may be related to loss of immune function. A role for apoptosis in the pathogenesis of AIDS is also supported by the strong correlation between viral load and rates of apoptosis in CD4+ T cells.

Antibody Formation↗
PubMed1997

[Hepatitis GBV isolated in acute liver failure. Successful outcome after liver transplantation].

Fulminant hepatic failure is a life-threatening condition associated with a mortality of approximately 80 per cent. Liver transplantation may be the only life-saving recourse in such cases. The condition can be caused by any of a number of different agencies such as viral infection, or toxic, circulatory or metabolic factors, though in a large proportion of cases the aetiology is unknown. Recently, knowledge has accumulated of a new hepatitis virus, hepatitis GB virus (HGBV), a Flavivirus remotely related to hepatitis C. The clinical significance of this virus is unclear. It is found in 3-4 per cent of blood donors, and most HGBV-positive patients are asymptomatic though some develop fulminant hepatic failure. The article consists in a case report of fulminant hepatic failure in a 17-year-old woman where no possible aetiological factor could be identified, other than her HGBV-positivity. The patient underwent a successful liver transplantation and is now, 18 months later, in excellent condition. She is still HGBV-positive but manifests no hepatic effects. Whether HGBV infection was responsible for the hepatic failure remains unclear, however.

Adolescent↗
PubMed1997

Prevalence and risk factors for HTLV-II infection in 913 injecting drug users in Stockholm, 1994.

The prevalence and risk factors for acquisition of human T-cell lymphotropic virus type I and II (HTLV-I and II) were investigated in a prospective study of 913 injecting drug users (IDUs) in Stockholm in 1994. Epidemiologic data were recorded, and blood samples were tested for antibodies against HTLV-I and HTLV-II; human immunodeficiency virus (HIV) types 1 and 2; and hepatitis A (HAV), B (HBV), C (HCV), and D (HDV). Positive serologic results for HTLV were confirmed by Western blot (WB) and polymerase chain reaction (PCR). Of the 905 participants with conclusive HTLV-II status, 29 (3.2%) were HTLV-II positive, and all but three were of Nordic descent. None was HTLV-I infected. One person was infected as early as 1981, before HIV had reached the IDU population in Sweden. The prevalence of HTLV-II infection was 12% among HIV-1-seropositive and 1.8% among HIV-1-seronegative participants. The overall seroprevalences were 14% for HIV-1, 0% for HIV-2, 41% for HAV, 75% for HBV, 92% for HCV, and 8% for HDV. Although amphetamine has been the main injecting drug in Sweden for several decades, heroin abuse combined with a debut of injecting drugs before 1975 was identified as the most important risk factor associated with HTLV-II infection. HAV and HIV seropositivity were also independent risk factors.

Adult↗
PubMed1997

Progressive B cell apoptosis and expression of Fas ligand during human immunodeficiency virus type 1 infection.

HIV-1 infection causes functional defects in T cells. It also leads to a progressive reduction in numbers of such cells and both CD4+ and CD8+ cells have been reported to undergo apoptosis in culture. A corresponding reduction in B cells has not been described, but these cells are also functionally altered, with reports of polyclonal activation and hyporesponsiveness to antigenic and mitogenic stimuli. Here we investigated B cells from HIV-1-seropositive individuals and found that these cells, which are not the target for virus infection, died of apoptosis on culturing. We could also confirm previous findings that CD4+ cells from HIV-1-infected individuals undergo apoptosis in culture. Apoptosis of both B cells and CD4+ cells correlated inversely with CD4 cell counts. B cells from HIV-1-infected individuals were found to express Fas ligand, and the expression of this protein correlated with the levels of apoptosis in the same cells. Non-B cells, on the other hand, expressed increased levels of Fas but low levels of Fas ligand. These results are in line with suggestions that the Fas/Fas ligand pathway may trigger the increased levels of apoptosis observed in cells from HIV-1-infected individuals.

Adult↗
PubMed1997

Dynamic analysis of hepatitis C virus polymorphism in patients with orthotopic liver transplantation.

BACKGROUND: The hepatitis C virus (HCV) quasispecies feature is important for HCV persistence. Most liver grafts are reinfected by HCV after liver transplantation (LTx). METHODS: The degree of HCV polymorphisms during LTx was determined by single-strand conformation polymorphism (SSCP) analysis and direct sequencing of the HCV hypervariable region 1 (HVR1). RESULTS: The number of HCV HVR1 SSCP bands in three patients decreased within 3 months after LTx as compared with before LTx. Direct sequencing of serial samples of one patient showed that the number of HVR1 polymorphic sites was lower at 1.5 months after LTx, and that the major sequence was identical to that before LTx. The number of both the HVR1 SSCP bands and the polymorphic sites after 3 months after LTx returned to a similar level as before LTx. CONCLUSIONS: Only a subset of the preexisting HCV variants replicates in the transplant liver graft. The limited immunological selective pressure within the first post-LTx period results in a homogenous HCV population that becomes more heterogenous after the first 3 months.

Amino Acid Sequence↗
PubMed1997

Dynamics of the HIV-1 subtype distribution in the Swedish HIV-1 epidemic during the period 1980 to 1993.

We have investigated the distribution of the major subtypes, or clades (A to E), in the Swedish human immunodeficiency virus type 1 (HIV-1) epidemic between the years 1980 to 1993, using gp120 V3 domain serotyping and genotyping. Until 1984 the Swedish HIV-1 epidemic was almost exclusively caused by HIV-1 subtype B. During the late 1980s and the early 1990s an increase in nonsubtype B infections (mainly subtypes A and C) was observed. Nonsubtype B infections constituted approximately 30% of the newly diagnosed HIV-1 cases in 1993. In the analyzed material we also noted a substantial increase in the proportion of HIV-1 infections caused by heterosexual transmission. The present data suggest that the subtype distribution in the Swedish HIV-1 epidemic may well continue to change with time, which may have implications for preventive research and vaccine development strategies.

DNA, Viral↗
PubMed1997

Quantification of HIV-1 proviral DNA from peripheral blood mononuclear cells using a high throughput four-competitor competitive PCR.

A multiple competitor PCR (mcPCR) was developed to quantify HIV-1 proviral DNA from peripheral blood mononuclear cells (PBMC). DNA extracted from a mixture of HIV infected PBMC and four size-mutated DNA competitors were co-amplified. The Cy5-fluorescence labelled PCR products were denatured by heating, separated using an automated DNA sequencer and quantified by a fragment analysis computer software. An internal standard was generated by plotting the peak areas of the four competitors against their inputs. Based on the internal standard, HIV sample DNA was quantified by extrapolating the corresponding signal. The linear range of the mcPCR was three log wide and the quantitation limit was about 20 copies of HIV DNA/10(6) PBMC. Using the mcPCR, HIV DNA was quantified from 14 long-term non progressors (LTNP) and 14 patients with advanced disease. A significantly lower copy number of HIV DNA was obtained in the LTNP (p = 0.018). These data suggest that the mcPCR is sensitive, reliable and especially useful for HIV DNA quantification of a large number of clinical samples.

DNA, Viral↗
PubMed1997

Variation of hepatitis C virus hypervariable region 1 in immunocompromised patients.

The viral variability of 5 hepatitis C virus (HCV)-infected immunocompromised patients was analyzed and compared with that in isolates from immunocompetent subjects. The patients were followed longitudinally with regard to changes in hypervariable region 1 (HVR1) of HCV using a direct DNA sequencing approach. For the immunocompromised patients, viral nucleotide sequence variability was markedly lower than in immunocompetent HCV-positive patients. For 1 agammaglobulinemic patient and 1 AIDS patient, no variation in the major amino acid sequence of HCV HVR1 could be observed, while another agammaglobulinemic patient exhibited transient variations and amino acid substitutions despite the lack of functioning humoral immune response. The study supports the general hypothesis of humoral immune selection as the main force of sequence variation in the HVR1 region but suggests that other selection mechanisms may contribute to modulation of the composition of the viral population.

Amino Acid Sequence↗
PubMed1997

Genetic evidence for mother-to-infant transmission of hepatitis G virus.

Mother-to-infant transmission of hepatitis G virus (HGV [or GBV-C]) was studied in sera from 42 mothers at high risk for bloodborne infections and from their 45 infants (3 twin pairs). Seven (17%) of the mothers had HGV RNA in serum by a polymerase chain reaction assay. One of the 8 (12.5%) infants born to HGV-infected mothers became positive for HGV at 3 months of age. He remained HGV-infected throughout the study (42 months), with no signs of liver disease. His twin sister remained HGV-negative despite the presence of serum and salivary HGV in both the mother and the brother. Analysis of HGV sequences from the infected mother and the infected child confirmed a genetic link between the virus of the mother and the infected child. Thus, mother-to-infant transmission of HGV, presumably occurring at partus, may cause persistent HGV viremia.

Amino Acid Sequence↗
PubMed1997

Subtype-specific problems with quantification of plasma HIV-1 RNA.

OBJECTIVE: To determine whether two commercial assays for quantification of plasma HIV-1 RNA levels detect different genetic subtypes of HIV-1 with equal efficiency. DESIGN: Blind testing of stored plasma samples from 95 individuals infected with different genetic subtypes of HIV-1 (27 subtype A, 24 B, 18 C, 18 D, two E, two G, two H, and two J). The HIV-1 subtype had previously been determined by direct sequencing of the V3 domain of the env gene. METHODS: One plasma sample from each individual was tested once by the Roche HIV monitor assay and once by the Organon nucleic acid sequence-based amplification (NASBA) HIV-1 RNA quantitative assay, according to the manufacturers' recommendations. Information about CD4+ lymphocyte counts and antiretroviral treatment was available. RESULTS: The results from the two assays were strongly correlated with each other for subtypes B, C and D, but not for subtype A because many samples had RNA levels close to or below the lower detection limit of the assays. Thus, 15 out of 27 (56%) subtype A samples were negative by the HIV monitor assay and 12 (44%) were negative by the NASBA assay. These frequently occurring negative results among subtype-A-infected individuals were not due to better immunological status, more aggressive antiretroviral treatment, or differences in sample storage conditions. CONCLUSIONS: The HIV monitor assay and, possibly to slightly lesser degree, the NASBA assay appear unable to accurately quantify HIV-1 RNA levels in plasma samples from many subtype-A-infected individuals. These problems are likely to be due to primer mismatches and they limit the possibility of using these assays for routine monitoring of HIV-1-infected individuals in many parts of the world.

CD4 Lymphocyte Count↗