| 1. |
- Zhang, Shu-min, et al.
(författare)
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Dynamic changes in hepatitis C virus genotypes and sequence patterns in plasma donors exposed to reinfection
- 2001
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Ingår i: Journal of Medical Virology. - 1096-9071. ; 63:3, s. 228-236
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Tidskriftsartikel (refereegranskat)abstract
- Sequential serum samples from four plasma donors (designated A, B, C, and D) at a Chinese blood bank with hepatitis C transmission problems were studied from 1994 to 1997. The samples were examined for antibodies to HCV, for HCV viremia by PCR and HCV genotyping. Co- and superinfections were studied by direct sequencing of the 5'-NCR, core, and HVR-1 regions, using low and high genotype-specific primers targeting the HVR-1, and by cloning of selected samples. Genotype changes occurred in all four donors: A (1b-2a-1b), B (1b-2a-2a/1b-1b), C (1b-2a), and D (1b/2a-1b). Donor D was married to donor B. The 1b isolates of donor A could not be sequenced in the HVR-1 due to low-level viremia. Two early 1b isolates from donors B and C showed high HVR-1 similarity. The later 1b isolates from B had changed significantly but were identical to the isolate from donor D. Spouses B and D also shared genotype 2a strains. The 2a isolates from donors A, B/D, and C differed by 8-10 nucleotides in the HVR-1. The frequent changes in genotype and the appearance of homologous isolates from different subjects indicate transmission at the blood bank. These four donors, all identified shortly after infection, developed very few mutations in the HVR-1 and few quasispecies during a period of 6-18 months. Highly specific primers proved to be superior to cloning for identification of minor virus populations. The results indicate nosocomial transmission of more than one strain at the blood bank studied.
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| 2. |
- Bläckberg, Jonas, et al.
(författare)
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Genotypic differences in the hepatitis B virus core promoter and precore sequences during seroconversion from HBeAg to anti-HBe
- 2000
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Ingår i: Journal of Medical Virology. - 1096-9071. ; 60:2, s. 107-112
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis B virus (HBV) strains from anti-HBe positive patients often show specific mutations in the precore gene, the core promoter region, or both. The dynamics of seroconversion in relation to the appearance of these mutations has not been studied and compared between defined HBV genotypes. Samples from patients followed during seroconversion from HBeAg to anti-HBe were amplified by polymerase chain reaction (PCR), sequenced and genotyped. Among 16 sets of samples, 6 belonged to genotype A, 6 to genotype D, 2 to genotype B, 1 to genotype C, and 1 to genotype E. Whereas strains from genotypes B, C and E showed changes in the core promoter, precore codon 28 or both, genotype A and D strains displayed a different pattern. In 4 of 6 anti-HBe positive samples from genotype A, the precore had a wild-type sequence while the core promoter sequence showed a specific TGA mutation. In another genotype A strain a precore stop mutation was preceded by a mutation in codon 15, thus conserving base-pairing at the pregenomic RNA level in this region. In contrast, all genotype D strains showed wild-type sequences in both the core promoter and precore codon 28 in pre- and post-seroconversion samples. Thus, in 8 patients with a mean follow-up time of 17 months, wild-type sequences in both the core promoter and precore codon 28 were found after seroconversion to anti-HBe. This study also confirmed, for genotype D, that HBeAg seroconversion often occurs earlier than genomic conversion.
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| 3. |
- Enbom, Malin, et al.
(författare)
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Antibodies to human herpesvirus 8 latent and lytic antigens in blood donors and potential high-risk groups in Sweden : variable frequencies found in a multicenter serological study
- 2000
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Ingår i: Journal of Medical Virology. - 0146-6615 .- 1096-9071. ; 62:4, s. 498-504
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Tidskriftsartikel (refereegranskat)abstract
- Human herpesvirus 8 (HHV-8) is a herpesvirus associated with Kaposi's sarcoma (KS). An immunofluorescence assay was used for detection of IgG, IgM, and IgA antibodies against lytic and latent HHV-8 antigens to analyse samples from KS patients (n = 8), healthy blood donors (n = 162), individuals with a high risk sexual behaviour (n = 114), and bone marrow transplant patients (with high risk for bloodborne infections) (n = 34) in Sweden. Of the KS patients, 88% had IgG antibodies to both lytic and latent antigens by immunofluorescence. In all other groups, antilatent antibodies were rare (0-2.6%). IgG antibodies to the lytic antigens were found, by immunofluorescence, in 20% of the blood donors, 31% of the high risk patients, and in 24 and 29% of the bone marrow transplant patients (pre- and post-transplant samples, respectively). For verification of the specificity of the anti-lytic antibodies, 170 of the samples were also tested blindly at different laboratories world-wide with five other assays shown previously to detect HHV-8 antibodies in most KS patients. By using two recombinant HHV-8 proteins (ORF65/vp17 and K8.1/gp 35-37) in ELISA, a whole-virion ELISA and two immunofluorescence assays confirmation of the reactivity against lytic viral antigens was sought. The comparison of the different methods suggested the K8.1 ELISA to be highly specific and also showed a good agreement between two of the immunofluorescence assays. However, generally there was a poor correlation for positive results, indicating the need of further methodological development.
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| 4. |
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| 5. |
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| 6. |
- Davydova, B., et al.
(författare)
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Coxsackievirus immunization delays onset of diabetes in non-obese diabetic mice
- 2003
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Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 69:4, s. 510-520
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Tidskriftsartikel (refereegranskat)abstract
- Enteroviruses may be involved in the pathogenesis of Type 1 diabetes through different mechanisms including triggering of autoimmunity. The effect of immunization with coxsackievirus B4-E2 on diabetes incidence was studied in the non-obese diabetic mice, an animal model for human autoimmune insulin-dependent diabetes mellitus. The immunization delayed the onset of diabetes in the mice, and the effect was mediated at least partially by virus immunization-activated splenocytes as demonstrated by adoptive transfer experiments. Immunization resulted in a strong humoral immune response against the immunizing virus, formalin-inactivated coxsackievirus B4-E2. Cell-mediated immune responseto virus antigen was characterised by interferon gamma and interleukin 10 secretion. The immunization also resulted in increased antibody levels against several beta-cell autoantigens. By using epitope mapping we were able to show that in addition to reactivity with the known epitopes of viral proteins and tyrosine phosphatase A-2 or heat shock protein 60, responses to some other regions of autoantigens were enhanced. In preproinsulin, the response was restricted against an antigenic region earlier identified as DR4-dependent epitope. This reactivity can not be explained by homologous amino acid sequences and it is possible that enterovirus immunization might change the autoantigen specific TH1/TH2 balance in non-obese diabetic mice. In conclusion, our results suggest that coxsackievirus immunization increased humoral immune response to beta cell autoantigens and this was associated with a less destructive pathology for spontaneous diabetes in non-obese diabetic mice. © 2003 Wiley-Liss, Inc.
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| 7. |
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| 8. |
- Forslund, Ola, et al.
(författare)
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Population-based type-specific prevalence of high-risk human papillomavirus infection in middle-aged Swedish Women.
- 2002
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Ingår i: Journal of Medical Virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 66:4, s. 535-541
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus (HPV) DNA testing can be used to identify women at risk of the development of cervical cancer. The cost-effectiveness of HPV screening is dependent on the type-specific HPV prevalence in the general population. The present study describes the prevalence and spectrum of high-risk HPV types found in a large real-life population-based HPV screening trial undertaken entirely within the cervical screening program offered to middle-aged Swedish women. Cervical brush samples from 6,123 women aged 32-38 years were analyzed using a general HPV primer (GP5(+)/6(+)) polymerase chain reaction-enzyme immunoassay (PCR-EIA) combined with reverse dot-blot hybridization for confirmation and HPV typing by a single assay. In this study, 6.8% (95% CI 6.2-7.5) (417/6,123) were confirmed as high-risk HPV positive. Infections with 13 different high-risk HPV types were detected, of which HPV 16 was the most prevalent type (2.1%; 128/6,123), followed by HPV 31 (1.1%; 67/6,123). Any one of the HPV types 18, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 66 was detected in 3.6% (223/6,123) of the women. Infection with two, three, and five types simultaneously was identified in 32, 5, and 1 women, respectively. The combination of PCR-EIA as a screening test and reverse dot-blot hybridization as a confirmatory test, was found to be readily applicable to a real-life population-based cervical screening. The type-specific HPV prevalence found support in previous modeling studies suggesting that HPV screening may be a favorable cervical screening strategy.
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| 9. |
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| 10. |
- Harkonen, T, et al.
(författare)
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Enterovirus infection may induce humoral immune response reacting with islet cell autoantigens in humans
- 2003
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Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 69:3, s. 426-440
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Tidskriftsartikel (refereegranskat)abstract
- Molecular mimicry is one of the mechanisms by which enterovirus infections have been postulated to have a role in the pathogenesis of type 1 diabetes. Immunogenic epitopes in enterovirus capsid protein VP1 and procapsid protein VP0 have sequence similarities with diabetes-associated epitopes in tyrosine phosphatase IA-2/IAR and heat shock protein 60. In the present study, documented enterovirus infection was shown to induce humoral responses, that in 7% and 1% of patients cross-reacted with the known diabetes-associated epitopes in tyrosine phosphatase IAR and heat shock protein 60, respectively. In contrast, none of the children vaccinated against poliomyelitis had antibodies to the diabetes-associated epitope of tyrosine phosphatases IA-2/IAR. The antibody response studied in serum samples from six patients with coxsackievirus A9 infection was mainly targeted to capsid protein VP1. Coxsackievirus A9 infection induced antibodies cross-reacted with one epitope in heat shock protein 60, but not with epitopes derived from other autoantigens. Most diabetic children had high levels of antibodies to both coxsackievirus and poliovirus derived VP1 peptides but the pattern of reactivity did not differ from that seen in healthy children. The reactivity of linear epitopes derived from autoantigens was low in general and associated with the presence of multiple autoantibodies in the patients. Some linear auto-epitopes derived from tyrosine phosphatase IA-2, glutamic acid decarboxylase 65, preproinsulin, and heat shock protein 60 were recognized by sera from diabetic patients, but not by sera from healthy children. In conclusion, enteroviruses may induce immune responses that react with islet cell autoantigens, which is a concern when a putative inactivated enterovirus vaccine is considered.
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