| 1. |
- Allander, T, et al.
(författare)
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Recombinant human monoclonal antibodies against different conformational epitopes of the E2 envelope glycoprotein of hepatitis C virus that inhibit its interaction with CD81
- 2000
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 81:10, s. 2451-2459
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Tidskriftsartikel (refereegranskat)abstract
- The antibody response to the envelope proteins of hepatitis C virus (HCV) may play an important role in controlling the infection. To allow molecular analyses of protective antibodies, we isolated human monoclonal antibodies to the E2 envelope glycoprotein of HCV from a combinatorial Fab library established from bone marrow of a chronically HCV-infected patient. Anti-E2 reactive clones were selected using recombinant E2 protein. The bone marrow donor carried HCV genotype 2b, and E2 used for selection was of genotype 1a. The antibody clones were expressed as Fab fragments in E. coli, and as Fab fragments and IgG1 in CHO cells. Seven different antibody clones were characterized, and shown to have high affinity for E2, genotype 1a. Three clones also had high affinity for E2 of genotype 1b. They all bind to conformation-dependent epitopes. Five clones compete for the same or overlapping binding sites, while two bind to one or two other epitopes of E2. Four clones corresponding to the different epitopes were tested as purified IgG1 for blocking the CD81-E2 interaction in vitro; all four were positive at 0.3-0.5 microg/ml. Thus, the present results suggest the existence of at least two conserved epitopes in E2 that mediate inhibition of the E2-CD81 interaction, of which one appeared immunodominant in this donor.
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| 2. |
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| 3. |
- Nilsson, Anna C, et al.
(författare)
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Longitudinal clearance of seasonal influenza A viral RNA measured by real-time polymerase chain reaction in patients identified at a hospital emergency department.
- 2010
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 42, s. 679-686
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Tidskriftsartikel (refereegranskat)abstract
- Abstract To study influenza virus shedding during acute infection, viral load was longitudinally measured by quantitative PCR in nasal flocked swabs from patients with seasonal H3N2 influenza at a Swedish emergency department, including both hospitalized patients and outpatients. Influenza A was detected in 65/184 patients. Sampling was repeated every 3-4 days in 45 patients, with the aim of continuing sampling until day 12 after disease onset. Home visits were offered. Antibodies were measured on paired sera in 95/184 patients. Fifty percent of the patients remained polymerase chain reaction (PCR)-positive 8 days after disease onset in a Kaplan-Meier survival curve. The longest observed duration of viral shedding was 12 days. The average viral load was initially low, peaked on days 2-3 of disease and then declined. Viral decline results remained similar when all 15 (25%) oseltamivir-treated patients were excluded. Significant antibody titre changes were seen in all the 35 PCR verified cases with available paired sera and in 8 of the 58 patients with negative PCR tests on acute phase nasal samples. In conclusion, quantitative PCR testing indicated the presence of influenza virus for up to 12 days, which could have implications for disease transmission and infection control.
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| 4. |
- Nilsson, Anna, et al.
(författare)
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Clinical severity of Mycoplasma pneumoniae (MP) infection is associated with bacterial load in oropharyngeal secretions but not with MP genotype.
- 2010
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 10:39
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Disease severity in Mycoplasma pneumoniae (MP) infection could potentially be related to bacterial factors such as MP genotype (MP1 or MP2; distinguished by different adhesions proteins) or bacterial load in airway secretions. We have compared these parameters in patients who were hospitalized for MP pneumonia, with outpatients with mild MP disease. METHODS: MP bacterial load was measured by real-time PCR in 45 in- and outpatients ("clinical study group") in whom MP DNA had been detected in oropharyngeal secretions by PCR. In addition, genotype and phylogenetic relationships were determined. The phylogenetical assessment was done by partial DNA sequencing of the P1 gene on isolates from 33 patients in the clinical study-group where sufficient DNA was available. The assessment was further extended to isolates from 13 MP-positive family members and 37 unselected MP positive patients from the two subsequent years and two different geographical locations. In total 83 strains were molecular characterized. RESULTS: Mean MP loads were significantly higher in 24 hospitalized patients than in 21 outpatients (1600 vs. 170 genomic equivalents/microL, p = 0.009). This difference remained significant after adjustment for age and days between disease onset and sampling. Hospitalized patients also had higher C-reactive protein levels. Mean levels were 188 vs 20 mg/L (p = 0,001). The genotype assessment showed MP genotype 1 in 17 of the 33 sequenced strains from the clinical study-group, and type 2 in 16 of these patients. Within each genotype, sequence differences were minimal. No association between disease severity and MP genotype was observed. In the extended genotype assessment, MP1 was found in similar proportions. In family contacts it was found in 53% and among patients from the two subsequent years 53% and 40%. CONCLUSIONS: A higher MP bacterial load in throat secretions at diagnosis was associated with more advanced respiratory disease in patients, but MP genotype did not influence disease severity. Both MP genotypes co-circulated during recent outbreaks in Sweden.
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| 5. |
- Widell, Anders, et al.
(författare)
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Epidemiologic and molecular investigation of outbreaks of hepatitis C virus infection on a pediatric oncology service
- 1999
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Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819. ; 130:2, s. 130-134
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite screening of blood donors, hepatitis C virus (HCV) infection can occur in patients who receive multiple transfusions. OBJECTIVE: To clarify mechanisms of nosocomial transmission of HCV. DESIGN: Epidemiologic and molecular analyses of hepatitis C outbreaks. SETTING: Pediatric oncology ward. PATIENTS: Children with cancer. MEASUREMENTS: Epidemiologic analysis, HCV RNA detection, genotyping, and hypervariable region 1 (HVR1) sequencing. RESULTS: Ten cases of infection with acute HCV genotype 3a occurred between 1990 and 1993. Sequencing of HVR1 revealed three related strains. Despite an overhaul of hygiene procedures, a patient infected with genotype 1b generated nine subsequent infected patients in 1994. Several patients had high virus titers and strongly delayed anti-HCV antibody responses. All had permanent intravenous catheters. Multidose vials used for flushing or treatment had probably been contaminated during periods of overlapping treatment. CONCLUSIONS: Contamination of multidose vials was the most likely mode of HCV transmission; therefore, use of such vials should be restricted. Rigorous adherence to hygiene routines remains essential to preventing transmission of bloodborne infections.
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| 6. |
- Widell, Anders, et al.
(författare)
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Hepatitis C superinfection in hepatitis C virus (HCV)-infected patients transplanted with an HCV-infected kidney
- 1995
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Ingår i: Transplantation. - 1534-6080. ; 60:7, s. 642-647
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis C virus (HCV) genotypes, determined by polymerase chain reaction with type-specific primers, were studied in 5 already HCV-infected patients receiving kidneys from HCV-infected cadaver donors. Three patients were investigated retrospectively using stored pre- and posttransplantation sera and followed 18-28 months after transplantation. Two recipients with HCV genotype 2b infection had received kidneys from 1 genotype 3a-infected donor. In 1 recipient, HCV 2b was replaced by the donor's type; in the other recipient, a prolonged mixed infection of 3a and 2b occurred. Persistent alanine aminotransferase (ALT) elevation (3- to 5-fold) appeared in both patients. The third patient, also HCV 2b infected when transplanted with an HCV 3a-infected kidney, remained infected with HCV 2b only. Two patients, one with HCV genotype 1b and the other with genotype 3a, were followed prospectively with frequent bleeds (initially biweekly) and genotyping over 14 months after they had received kidneys from 1 HCV genotype 1a-infected donor. The HCV 1b-infected recipient remained infected with 1b only and had minimal biochemical signs of liver injury. In the other recipient, mixed infection of 3a and 1a appeared at week 3 and persisted for several weeks, until only genotype 1a could be detected. This patient had elevated ALT levels before transplantation. After onset of mixed infection, ALT levels increased further for several weeks, and returned to pretransplantation levels when only HCV 1a was found. HCV-infected kidneys transplanted into HCV-infected recipients gave 3 different virus patterns. Most patients benefitted in the short term, but some super-infected patients experienced increased liver damage.
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