| 1. |
- Eriksson, Kristina, 1962, et al.
(författare)
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CD4(+) T-cell responses to herpes simplex virus type 2 (HSV-2) glycoprotein G are type specific and differ in symptomatic and asymptomatic HSV-2-infected individuals
- 2004
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Ingår i: J Gen Virol. - 0022-1317. ; 85:Pt 8, s. 2139-47
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Tidskriftsartikel (refereegranskat)abstract
- T-cell recognition of the secreted and membrane-bound portions of the herpes simplex virus type 2 (HSV-2) glycoprotein G (sgG-2 and mgG-2, respectively) was compared in symptomatic and asymptomatic HSV-2-infected individuals and in HSV-2-seronegative controls and the responses with HSV-1 glycoproteins C and E (gC-1 and gE-1) were compared. CD4(+) T cells from HSV-2-infected individuals specifically recognized both sgG-2 and mgG-2, whereas HSV-1-infected and HSV-seronegative controls did not respond to these glycoproteins. The responses to gC-1 and gE-1, on the other hand, were not type specific, as blood mononuclear cells from both HSV-1- and HSV-2-infected individuals responded in vitro. There was an association between the status of the infection (symptomatic versus asymptomatic) and the CD4(+) T-cell responsiveness. Symptomatic HSV-2-seropositive individuals responded with significantly lower Th1 cytokine production to sgG-2 and mgG-2 than did asymptomatic HSV-2-infected carriers, especially within the HSV-1-negative cohort. No differences in T-cell proliferation were observed between asymptomatic and symptomatic individuals. The results have implications for studies of HSV-2-specific CD4(+) T-cell reactivity in general and for analysis of immunological differences between asymptomatic and symptomatic individuals in particular.
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| 2. |
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| 3. |
- Löwhagen, Gun-Britt, 1942, et al.
(författare)
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Proportion of herpes simplex virus (HSV) type 1 and type 2 among genital and extragenital HSV isolates.
- 2002
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Ingår i: Acta dermato-venereologica. - 0001-5555. ; 82:2, s. 118-20
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus type 1 (HSV-1) has been associated with orofacial infections and HSV type 2 (HSV-2) with genital infections. This tropism of the virus seems to have changed and in clinical reports an increasing number of genital herpes infections caused by HSV-1 have been recognized. The aim of this study was to estimate the proportion of HSV-1 and HSV-2, respectively, among isolates from different anatomical sites typed in our laboratory during the years 1994-1998. Out of a total of 3,085 anogenital isolates, 29% were typed as HSV-1 and 71% as HSV-2. The highest prevalence of HSV-1 was registered among isolates from young women. Of 631 orofacial isolates, 4% were typed as HSV-2 and 96% as HSV-1. Of 69 finger/hand isolates, 54% were typed as HSV-1 and 46% as HSV-2, and of 95 isolates from other regions (abdomen, foot, etc.), 60% were typed as HSV-1 and 40% as HSV-2. It was found that HSV-2 was as common as HSV-1 in the extra-genital regions with the exception of the orofacial area, in which HSV-2 was seldom detected. Furthermore, the study showed an increasing proportion of HSV-1 among anogenital isolates during the study period. Taken together, these results suggest that a clear HSV type-related tropism might be limited to the permissiveness of the orofacial region for HSV-1, and that both serotypes may readily establish infections below the neck.
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| 4. |
- Löwhagen, Gun-Britt, 1942, et al.
(författare)
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Recurrent genital herpes in a population attending a clinic for sexually transmitted diseases.
- 2001
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Ingår i: Acta dermato-venereologica. - 0001-5555. ; 81:1, s. 35-7
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Tidskriftsartikel (refereegranskat)abstract
- Patients with recurrent genital herpes attending a sexually transmitted disease clinic were studied and transmission of the infection was elucidated by evaluating serostatus in their partners. Of 84 patients attending for recurrent genital herpes, 94% had a herpes simplex virus type 2 (HSV-2) infection and only 6% (5 patients) a type 1 infection. The mean age of the patients was 36 years and the duration of their infection was up to 37 years (median 4 years). In most patients the number of recurrences had not decreased between the first year and the last year. About half had experienced a more severe first episode infection. Of the patients, 64% were not aware of asymptomatic shedding and the risk of sexual transmission without clinical symptoms. Of 67 steady partners of patients with genital HSV-2, 15% had a history of genital herpes. By HSV serology, HSV-2 antibodies (indicating subclinical genital herpes) were demonstrated in more than half of the partners. The duration of the relationship or condom use did not seem to influence the frequency of transmission to the partner, which may indicate an individual susceptibility for acquiring a genital HSV-2 infection. Eleven per cent of the patients were on suppressive antiviral therapy, while 39% had no experience of antiviral therapy. Type-specific HSV serology was found to be of value in counselling partners of patients with genital herpes.
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| 5. |
- Löwhagen, Gun-Britt, 1942, et al.
(författare)
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Self-reported herpes labialis in a Swedish population.
- 2002
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Ingår i: Scandinavian journal of infectious diseases. - 0036-5548. ; 34:9, s. 664-7
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Tidskriftsartikel (refereegranskat)abstract
- In a cross-sectional study, the occurrence of a self-reported history of labial herpes was evaluated. The study population comprised a stratified random sample of 5,000 individuals, aged 0-60 y, from south-west Sweden. A questionnaire, together with written and photographic descriptions of labial herpes lesions, was sent to the participants. Of 5,000 questionnaires sent out, 3597 (72%) were returned. In answer to the question "Have you ever had herpes?" the point estimate was 26.6% (95% confidence interval [CI] 25.1%-28.1%) and for the question "Have you had herpes in the last 2 y?" it was 19.4 (95% CI 18.0-20.8). The proportion of individuals who had had herpes was higher for the older age groups. About 5% of children aged < or = 5 y had experienced labial herpes. Herpes was more frequently reported by females than males: odds ratio 1.29 (95% CI 1.10-1.51). Compared to previous studies in Sweden, our data do not indicate that the occurrence of labial herpes lesions has decreased.
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| 6. |
- Rekabdar, Elham, 1971, et al.
(författare)
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Dichotomy of glycoprotein g gene in herpes simplex virus type 1 isolates.
- 2002
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Ingår i: Journal of clinical microbiology. - 0095-1137. ; 40:9, s. 3245-51
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus type 1 (HSV-1) encodes 11 envelope glycoproteins, of which glycoprotein G-1 (gG-1) induces a type-specific antibody response. Variability of the gG-1 gene among wild-type strains may be a factor of importance for a reliable serodiagnosis and typing of HSV-1 isolates. Here, we used a gG-1 type-specific monoclonal antibody (MAb) to screen for mutations in the immunodominant region of this protein in 108 clinical HSV-1 isolates. Of these, 42 isolates showed no reactivity to the anti-gG-1 MAb. One hundred five strains were further examined by DNA sequencing of the middle part of the gG-1 gene, encompassing 106 amino acids including the immunodominant region and epitope of the anti-gG-1 MAb. By phylogenetic comparisons based on the sequence data, we observed two (main) genetic variants of the gG-1 gene among the clinical isolates corresponding to reactivity or nonreactivity to the anti-gG-1 MAb. Furthermore, four strains appeared to be recombinants of the two gG-1 variants. In addition, one strain displayed a gG-1-negative phenotype due to a frameshift mutation, in the form of insertion of a cytosine nucleotide. When immunoglobulin G reactivity to HSV-1 in sera from patients infected with either of the two variants was investigated, no significant differences were found between the two groups, either in a type-common enzyme-linked immunosorbent assay (ELISA) or in a type-specific gG-1 antigen-based ELISA. Despite the here-documented existence of two variants of the gG-1 gene affecting the immunodominant region of the protein, other circumstances, such as early phase of infection, might be sought for explaining the seronegativity to gG-1 commonly found in a proportion of the HSV-1-infected patients.
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| 7. |
- Tunbäck, Petra, 1965, et al.
(författare)
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Glycoprotein G of herpes simplex virus type 1: identification of type-specific epitopes by human antibodies.
- 2000
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Ingår i: The Journal of general virology. - 0022-1317. ; 81:Pt 4, s. 1033-40
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Tidskriftsartikel (refereegranskat)abstract
- Serological diagnosis of herpes simplex virus (HSV) infections requires assays based on antigens that expose type-specific determinants. This study was designed to outline the B-cell epitopes of the type-specific glycoprotein G-1 (gG-1) of HSV type 1 (HSV-1), by investigating the reactivity of human anti-gG-1 antibodies, purified from 21 HSV-1-isolation-proven patient sera, to cellulose-bound synthetic peptides spanning the entire gG-1 sequence. The epitope mapping demonstrated that these antibodies bound preferentially to antigenic determinants that localized to regions with a high degree of amino acid similarity to the corresponding glycoprotein in HSV-2, gG-2. In spite of this, the purified anti-gG-1 antibodies were found to be non-reactive to native gG-2 antigen, as well as to overlapping gG-2 peptides, thus supporting the role of gG-1 as a prototype HSV-1 type-specific antigen. One immunodominant region, delimited by amino acids 112-127, reacted with all purified anti-gG-1 antibodies and may be of interest for the further development of a peptide-based HSV-1 type-specific seroassay.
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| 8. |
- Tunbäck, Petra, 1965
(författare)
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Herpes simplex virus infection: epidemiological aspects and analysis of the type-specific antibody response
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are ubiquitous viruses, often leading to asymptomatic infections in humans. However, different clinical presentations can be seen including recurrent oral or genital lesions, meningitis and neonatal herpes. HSV-1 and HSV-2 are closely related viruses carrying a genetic homology of 50 %, which has hampered the attempts to differentiate between the two types serologically. Due to the sometimes asymptomatic nature of the HSV-infection, serology can be the only way to diagnose an infection. Type-specific HSV-serology can also be used for epidemiological studies, for counseling in the clinical situation and in evaluating HSV vaccine trials. The envelope glycoproteins G-1 (gG-1) of HSV-1 and gG-2 of HSV-2 are the only known glycoproteins inducing type-specific antibody responses and are now utilized as discriminating ELISA antigens. A prerequisite for type-specific seroassays is, however, that these test are based on genetically stable antigens inducing only type-specific antibodies. In this thesis the B-cell epitopes, including an immunodominant region, have been outlined for gG-1 using the pepscan method. Unexpectedly, the epitopes were mainly localized to regions carrying a high degree of homology to gG-2. Despite this, analysis of purified human anti-gG-1 antibodies displayed no reactivity to the gG-2 antigen. The type-specificity was further explored, after finding two corresponding highly homologous epitopic regions in gG-1 and gG-2, inducing type-specific antibody-responses. Mutational analysis demonstrated that this type-specific reactivity relied on single or dual key residues and was dependant on the structural presentation of these peptides, as shown by molecular modeling. The DNA sequence of gG-1 in clinical isolates was examined, showing that missense mutations affecting the immunodominant region occur. By phylogenetic comparison two different genotypes were established, but the serological response in patients infected with either of these two genotypes did not differ in their IgG reactivity in the gG-1 based ELISA. The type-specific HSV-serology was applied in the clinical setting, using it as a tool for classifying first episodes of genital herpes and clarifying transmission routes. Results revealed that over 60 % of primary genital infections were caused by HSV-1 and that almost 20 % of first episodes of genital herpes were, in fact, the first clinical recurrence of an earlier acquired HSV-2 infection. A suggested explanation to the rise in genital infections caused by HSV-1 has been a decrease of HSV-1 among children. Therefore an epidemiological study was conducted in Swedish children and adolescents, using the type-specific HSV-ELISA:s. In total, HSV-1 IgG antibodies were found in 31 % and HSV-2 IgG antibodies in 0.5 %. The HSV-1 infection seemed to be acquired early in life, with a seroprevalence of over 20 % in the cohort of 1-2 year olds, increasing with higher age. The seroprevalence in the oldest age-cohort did not differ significantly from the HSV-seroprevalence seen in earlier Swedish studies.
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| 9. |
- Tunbäck, Petra, 1965, et al.
(författare)
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Prevalence of herpes simplex virus antibodies in childhood and adolescence: a cross-sectional study.
- 2003
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Ingår i: Scandinavian journal of infectious diseases. - 0036-5548. ; 35:8, s. 498-502
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Tidskriftsartikel (refereegranskat)abstract
- The changing spectrum of herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infections makes it important to define the seroepidemiology of HSV. The object of this study was to determine the prevalence of HSV-1 and HSV-2 immunoglobulin G antibodies in a young Swedish population by investigating 2106 serum samples from people aged 0-19 y. Sera were tested in HSV type-specific enzyme-linked immunosorbent assays using glycoprotein G-1 (gG-1) and glycoprotein G-2 (gG-2) as antigens. The overall seroprevalence was 31% (95% CI 29-33) for HSV-1 and 0.5% (95% CI 0.2-0.9) for HSV-2. The HSV-1 seroprevalence was higher with increasing age, and significantly higher in the age cohort 15-19 y compared with 1-4-y-olds (37% vs 24%). The HSV-1 infection seemed to be acquired early in life. In the age cohort 1-2 y, the prevalence was over 20%, presumably reflecting an established viral infection. In adolescence the HSV-1 seroprevalence may reflect both oral and sexual transmission. The seroprevalence in the oldest age cohort did not differ significantly from that seen in a Swedish study in which sera were sampled from young girls in the 1970s.
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