| 1. |
- Albert, J., et al.
(författare)
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Risk of HIV transmission from patients on antiretroviral therapy: A position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy
- 2014
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 46:10, s. 673-677
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Tidskriftsartikel (refereegranskat)abstract
- The modern medical treatment of HIV with antiretroviral therapy (ART) has drastically reduced the morbidity and mortality in patients infected with this virus. ART has also been shown to reduce the transmission risk from individual patients as well as the spread of the infection at the population level. This position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy is based on a workshop organized in the fall of 2012. It summarizes the latest research and knowledge on the risk of HIV transmission from patients on ART, with a focus on the risk of sexual transmission. The risk of transmission via shared injection equipment among intravenous drug users is also examined, as is the risk of mother-to-child transmission. Based on current knowledge, the risk of transmission through vaginal or anal intercourse involving the use of a condom has been judged to be minimal, provided that the person infected with HIV fulfils the criteria for effective ART. This probably also applies to unprotected intercourse, provided that no other sexually transmitted infections are present, although it is not currently possible to fully support this conclusion with direct scientific evidence. ART is judged to markedly reduce the risk of blood-borne transmission between people who share injection equipment. Finally, the risk of transmission from mother to child is very low, provided that ART is started well in advance of delivery.
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| 2. |
- Bellner, Lars, 1973, et al.
(författare)
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Characterization of T-cell reactive epitopes in glycoprotein G of herpes simplex virus type 2 using synthetic peptides.
- 2005
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Ingår i: Archives of virology. - : Springer Science and Business Media LLC. - 0304-8608 .- 1432-8798. ; 150:7, s. 1393-406
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that the CD4+ T-cell response to herpes simplex virus type 2 glycoprotein G-2 is type-specific and can thus be used to evaluate herpes simplex virus type 2-specific T-cell responses in individuals with a concomitant herpes simplex virus type 1 infection. In this study we have followed the glycoprotein G-2-specific T-cell responses over time, and also tried to identify T-cell epitopes in the membrane bound portion and the secreted portion of glycoprotein G-2 using synthetic peptides spanning the whole amino acid sequence of glycoprotein G-2. We found that the magnitude of the glycoprotein G-2-specific response varied considerably in infected individuals over time, even though all patients responded to at least one of the two glycoproteins at all time-points examined. We could also document strong T-cell responses to synthetic peptides from the secreted glycoprotein G-2 but only low responses to synthetic peptides corresponding to sequences from the heavily glycosylated membrane-bound glycoprotein G-2. We were able to map an immunogenic region (amino acid 31-125) within the secreted glycoprotein G-2. This region of the glycoprotein induced proliferative responses in 47% of the herpes simplex virus type 2-infected individuals. However, we were not able to identify any universal T-cell epitope.
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| 3. |
- Berntsson, Matilda, 1968, et al.
(författare)
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Viral and bacterial aetiologies of male urethritis: findings of a high prevalence of Epstein-Barr virus
- 2010
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Ingår i: International Journal of STD & AIDS. - 0956-4624. ; 21:3, s. 191-194
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Tidskriftsartikel (refereegranskat)abstract
- Male urethritis is one of the most common sexually transmitted infections (STIs). However, the aetiology is still unclear in many cases. In this study the prevalences of Epstein-Barr virus (EBV), herpes simplex virus type 1 (HSV-1), HSV-2, cytomegalovirus (CMV), adenovirus, Chlamydia trachomatis, Mycoplasma genitalium and Ureaplasma urealyticum (including subtyping) were investigated. Samples from 112 male STI attendants with microscopically verified urethritis and from a control group of 103 men without clinical or microscopic signs of urethritis were analysed. Prevalences in the urethritis group compared with the controls were as follows: EBV 21%, 6% (P < 0.01); C. trachomatis 15%, 3% (P < 0.01); M. genitalium 6%, 1% (P = 0.067) and U. urealyticum 10%, 10% (ns). The results for HSV-1, HSV-2, CMV and adenovirus were negative in patients, and therefore not analysed in the controls. EBV was shown to be an independent predictor of urethritis and may play a role in its pathogenesis.
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| 4. |
- Edén, Arvid, 1975, et al.
(författare)
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Differential effects of efavirenz, lopinavir/r, and atazanavir/r on the initial viral decay rate in treatment naïve HIV-1-infected patients.
- 2010
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Ingår i: AIDS research and human retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 26:5, s. 533-40
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Tidskriftsartikel (refereegranskat)abstract
- Initial viral decay rate may be useful when comparing the relative potency of antiretroviral regimens. Two hundred twenty-seven ART-naïve patients were randomized to receive efavirenz (EFV) (n = 74), lopinavir/ritonavir (LPV/r) (n = 77), or atazanavir/ritonavir (ATV/r) (n = 79) in combination with two NRTIs. The most frequently used NRTI combinations in the EFV and ATV/r groups were the nonthymidine analogues tenofovir and emtricitabine or lamivudine (70% and 68%, respectively) and, in the LPV/r group, lamivudine and the thymidine analogue zidovudine (89%). HIV-1 RNA was monitored during the first 28 days after treatment initiation. Phase 1 and 2 decay rate was estimated in a subset of 157 patients by RNA decrease from days 0 to 7, and days 14 to 28. One-way ANOVA and subsequent Tukey's post hoc tests were used for groupwise comparisons. Mean (95% CI) HIV-1 RNA reductions from days 0 to 28 were 2.59 (2.45-2.73), 2.42 (2.27-2.57), and 2.13 (2.01-2.25) log(10) copies/ml for the EFV-, LPV/r-, and ATV/r-based treatment groups, respectively, with a significantly larger decrease in the EFV-based group at all time points compared with ATV/r (p < 0.0001), and with LPV/r at days 7-21 (p < 0.0001-0.03). LPV/r gave a greater RNA decrease compared with ATV/r from day 14 (p = 0.02). Phase 1 decay rate was significantly higher in the EFV group compared with LPV/r (p = 0.003) or ATV/r (p < 0.0001). No difference was found in phase 2 decrease. EFV-based treatment gave a more rapid decline in HIV-1 RNA than did either of the boosted protease inhibitor-based regimens. The observed differences may reflect different inherent regimen potencies.
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| 5. |
- 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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| 6. |
- Eriksson, Kristina, 1962, et al.
(författare)
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Cutting Edge: Genetic Association between IFI16 Single Nucleotide Polymorphisms and Resistance to Genital Herpes Correlates with IFI16 Expression Levels and HSV-2-Induced IFN-β Expression.
- 2017
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 199:8, s. 2613-2617
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Tidskriftsartikel (refereegranskat)abstract
- IFN-γ-inducible protein 16 (IFI16) is an immunological DNA sensor proposed to act in the cyclic GMP-AMP synthase-stimulator of IFN genes pathway. Because mice do not have a clear ortholog of IFI16, this system is not suitable for genetic studies of IFI16. In this study, we have compared the dependency on IFI16, cyclic GMP-AMP synthase, and stimulator of IFN genes for type I IFN induction by a panel of pathogenic bacteria and DNA viruses. The IFN response induced by HSV-2 was particularly dependent on IFI16. In a cohort of patients with genital herpes and healthy controls, the minor G allele of the IFI16 single nucleotide polymorphism rs2276404 was associated with resistance to infection. Furthermore, the combination of this allele with the C allele of rs1417806 was significantly overrepresented in uninfected individuals. Cells from individuals with the protective GC haplotype expressed higher levels of IFI16 and induced more IFN-β upon HSV-2 infection. These data provide genetic evidence for a role for IFI16 in protection against genital herpes.
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| 7. |
- Kantere, Despoina, et al.
(författare)
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Clinical Features, Complications and Autoimmunity in Male Lichen Sclerosus.
- 2017
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Ingår i: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 97:3, s. 365-369
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Tidskriftsartikel (refereegranskat)abstract
- Lichen sclerosus is a chronic inflammatory disease associated with substantial morbidity. Knowledge of the aetiology and progression of lichen sclerosus is therefore needed. In this cross-sectional study, 100 male patients diagnosed with lichen sclerosus were interviewed and examined. Since there is a possible link between lichen sclerosus and autoimmunity, blood tests were analysed for thyroid disease, antinuclear antibodies and antibodies to extracellular matrix protein 1, but autoimmunity was found to be infrequent. In 72 participants active genital lichen sclerosis was observed and complications were common; 27 patients had preputial constriction and 12 meatal engagement. In total, 13 patients needed a referral to the Department of Urology, including 1 patient with suspected penile cancer. In conclusion, despite available treatment with ultra-potent steroids and circumcision, LS in males is frequently complicated by phimosis and meatal stenosis. However, the disease can also go into remission, as seen in 27% of our patients.
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| 8. |
- Lagergård, Teresa, 1946, et al.
(författare)
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Distribution of Chlamydia trachomatis ompA genovars and the new variant of C. trachomatis in the Göteborg area, Sweden.
- 2010
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Ingår i: European journal of clinical microbiology & infectious diseases. - : Springer Science and Business Media LLC. - 1435-4373 .- 0934-9723. ; 29:5, s. 609-611
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were to assess the proportion of the new variant of Chlamydia trachomatis (nvCT) and the distribution of ompA genovars among C. trachomatis-positive patients in the Göteborg area, Sweden. Consecutive urine samples positive for C. trachomatis using BD ProbeTec ET (177 patients, 88 men and 89 women) were collected. An nvCT-specific real-time polymerase chain reaction (PCR) assay was used to investigate the nvCT prevalence. To identify the genovars, a 990-bp ompA DNA segment from 105 specimens was sequenced. Seventeen percent (30/177) of all specimens contained nvCT. Nine different genovars were identified. About 50% were of genovar E, followed by F 16%, G 11%, K 8%, and D 5%, representing about 90% of the specimens in Göteborg. The occurrence of nvCT and the dominance of genovar E in Göteborg is similar to those in other areas of Sweden. To cover about 90% of the C. trachomatis infections in Sweden, the serovars D, E, F, G, and K should be included in future vaccines based on the major outer membrane protein.
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| 9. |
- Liljeqvist, Jan-Åke, 1954, et al.
(författare)
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Asymptomatically shed recombinant herpes simplex virus type 1 strains detected in saliva
- 2009
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 90:Pt 3, s. 559-66
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus type 1 (HSV-1) is a ubiquitous pathogen infecting most individuals worldwide. The majority of HSV-1-infected individuals have no clinical symptoms but shed HSV-1 asymptomatically in saliva. Recent phylogenetic analyses of HSV-1 have defined three genetic clades (A-C) and recombinants thereof. These data have all been based on clinical HSV-1 isolates and do not cover genetic variation of asymptomatically shed HSV-1. The primary goal of this study was to investigate such variation. A total of 648 consecutive saliva samples from five HSV-1-infected volunteers was collected. Asymptomatic shedding was detected on 7.6 % of the days from four subjects. The HSV-1 genome loads were quantified with real-time PCR and varied from 1x10(2) to 2.8x10(6) copies of virus DNA (ml saliva)(-1). Phylogenetic network analyses and bootscanning were performed on asymptomatically shed HSV-1. The analyses were based on DNA sequencing of the glycoprotein I gene, and also of the glycoprotein E gene for putative recombinants. For two individuals with clinical HSV-1 infection, the same HSV-1 strain was shed asymptomatically as induced clinical lesions, and sequence analyses revealed that these strains clustered distinctly to clades A and B, respectively. For one of the subjects with no clinical HSV-1 infection, a recombinant strain was identified. The other truly asymptomatic individual shed evolutionarily distinct HSV-1 strains on two occasions. The first strain was classified as a recombinant and the other strain clustered in clade A. High replication rates of different strains in the same person may facilitate the creation of recombinant clinical HSV-1 strains.
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| 10. |
- Liljeqvist, Jan-Åke, 1954, et al.
(författare)
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Human Antibodies against Herpes Simplex Virus 2 Glycoprotein G Do Not Neutralize but Mediate Antibody-Dependent Cellular Cytotoxicity
- 2024
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Ingår i: ANTIBODIES. - 2073-4468. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus 2 (HSV-2) is a sexually transmitted infection affecting 491 million individuals globally. Consequently, there is a great need for both prophylactic and therapeutic vaccines. Unfortunately, several vaccine clinical trials, primarily employing the glycoprotein D of HSV-2 (gD-2), have failed. The immune protection conferred by human anti-HSV-2 antibodies in genital infection and disease remains elusive. It is well-known that gD-2 elicits cross-reactive neutralizing antibodies, i.e., anti-gD-2 antibodies recognize gD in HSV-1 (gD-1). In contrast, anti-glycoprotein G in HSV-2 (mgG-2) antibodies are exclusively type-specific for HSV-2. In this study, truncated versions of gD-2 and mgG-2 were recombinantly produced in mammalian cells and used for the purification of anti-gD-2 and anti-mgG-2 antibodies from the serum of five HSV-2-infected subjects, creating a pool of purified antibodies. These antibody pools were utilized as standards together with purified mgG-2 and gD-2 antigens in ELISA to quantitatively estimate and compare the levels of cross-reactive anti-gD-1 and anti-gD-2 antibodies, as well as anti-mgG-2 antibodies in sera from HSV-1+2-, HSV-2-, and HSV-1-infected subjects. The median concentration of anti-mgG-2 antibodies was five times lower in HSV-1+2-infected subjects as compared with cross-reactive anti-gD-1 and anti-gD-2 antibodies, and three times lower in HSV-2 infected subjects as compared with anti-gD-2 antibodies. The pool of purified anti-gD-2 antibodies presented neutralization activity at low concentrations, while the pool of purified anti-mgG-2 antibodies did not. Instead, these anti-mgG-2 antibodies mediated antibody-dependent cellular cytotoxicity (ADCC) by human granulocytes, monocytes, and NK-cells, but displayed no complement-dependent cytotoxicity. These findings indicate that antibodies to mgG-2 in HSV-2-infected subjects are present at low concentrations but mediate the killing of infected cells via ADCC rather than by neutralizing free viral particles. We, and others, speculate that Fc-receptor mediated antibody functions such as ADCC following HSV-2 vaccination may serve as a better marker of protection correlate instead of neutralizing activity. In an mgG-2 therapeutic vaccine, our findings of low levels of anti-mgG-2 antibodies in HSV-2-infected subjects may suggest an opportunity to enhance the immune responses against mgG-2. In a prophylactic HSV-2 mgG-2 vaccine, a possible interference in cross-reactive immune responses in already infected HSV-1 subjects can be circumvented.
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| 11. |
- Löwhagen, Gun-Britt, 1942, et al.
(författare)
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Acceptance and outcome of herpes simplex virus type 2 antibody testing in patients attending an STD clinic--recognized and unrecognized infections
- 2005
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Ingår i: Acta Derm Venereol. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 85:3, s. 248-52
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Tidskriftsartikel (refereegranskat)abstract
- The majority of herpes simplex virus type 2 (HSV-2) genital infections are asymptomatic. We wanted to evaluate the acceptance of HSV-2 antibody testing among people attending an STD clinic and to estimate, after counselling, the percentage of recognized and unrecognized HSV-2 infections. First visitors to an STD clinic were invited to participate by answering a questionnaire and taking a blood test for HSV-2 antibodies. HSV-2 seropositive individuals, who were unaware of having genital herpes, were offered an HSV-2 counselling visit and follow-up. Of 1769 patients offered testing, 57% accepted. Of 152 (15%) HSV-2 seropositive individuals, 41% had a self-reported history of genital herpes, approximately 30% had genital symptoms and 30% had no genital symptoms. The percentage of patients reporting genital symptoms was much higher in HSV-2 seropositives (45%) without a history of genital herpes than in an HSV-2 seronegative group (28%). HSV-2 antibody testing should be performed generously in all cases of uncharacteristic genital symptoms.
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| 12. |
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| 13. |
- 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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| 14. |
- 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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| 15. |
- 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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| 16. |
- Löwhagen, Gun-Britt, 1942, et al.
(författare)
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The microenvironment of vulvar skin in women with symptomatic and asymptomatic herpes simplex virus type 2 (HSV-2) infection
- 2006
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Ingår i: J Eur Acad Dermatol Venereol. - : Wiley. - 0926-9959. ; 20:9, s. 1086-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is not known why some individuals infected with herpes simplex virus type 2 (HSV-2), experience frequent recurrences, while most of those infected have a completely silent infection. OBJECTIVE: We wanted to study if local factors in the skin could explain this difference. DESIGn 21 HSV-2 seropositive patients, 10 with history of >8 clinical recurrences a year (symptomatics) and 11 without symptoms of genital herpes (asymptomatics) were included. All had to answer a questionnaire. With standardised methods, the skin temperature, pH, and the skin barrier function, expressed as transepidermal water loss (TEWL) and skin capacitance, were measured on labium majus and perineum. Culture for bacteria was performed from the same regions. RESULTS AND CONCLUSION: No significant differences in terms of pH and skin barrier function were registered between symptomatic and asymptomatic patients. Asymptomatic patients had a tendency (0.06) to a higher colonisation with lactobacilli on labium majus than symptomatic patients.
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| 17. |
- 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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| 18. |
- Rekabdar, Elham, 1971, et al.
(författare)
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Variability of the glycoprotein G gene in clinical isolates of herpes simplex virus type 1.
- 1999
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Ingår i: Clinical and diagnostic laboratory immunology. - 1071-412X. ; 6:6, s. 826-31
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Tidskriftsartikel (refereegranskat)abstract
- Glycoprotein G (gG) of herpes simplex virus type 1 (HSV-1) has been used as a prototype antigen for HSV-1 type-specific serodiagnosis, but data on the sequence variability of the gene coding for this protein in wild-type strains are lacking. In this study, direct DNA sequencing of the gG-1 genes from PCR products was performed with clinical HSV-1 isolates from 11 subjects as well as with strains Syn 17(+), F, and KOS 321. The reference strains Syn 17(+) and F showed a high degree of conservation, while KOS 321 carried 13 missense mutations and, in addition, 12 silent mutations. Three clinical isolates showed mutations leading to amino acid alterations: one had a mutation of K(122) to N, which is a gG-1-to-gG-2 alteration; another contained all mutations which were observed in KOS 321 except two silent mutations; and the third isolate carried five missense mutations. Two clinical isolates as well as strain KOS 321 showed a mutation (F(111)-->V) within the epitope of a gG-1-reactive monoclonal antibody (MAb). When all viruses were tested for reactivity with the anti-gG-1 MAb, the three strains with the F(111)-->V mutation were found to be unreactive. Furthermore, gG-1 antibodies purified from sera from the two patients carrying strains mutated in this epitope were less reactive when they were tested by an HSV-1-infected-cell assay. Therefore, our finding that the sequence variability of the gG-1 gene also affects B-cell epitope regions of this protein in clinical isolates may have consequences for the use of this protein as a type-specific antigen for serodiagnosis.
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| 19. |
- Svensson, Alexandra, 1978, et al.
(författare)
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A 3'-untranslated region polymorphism in the TBX21 gene encoding T-bet is a risk factor for genital herpes simplex virus type 2 infection in humans.
- 2008
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 89:Pt 9, s. 2262-8
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Tidskriftsartikel (refereegranskat)abstract
- It was recently shown that the transcription factor T-bet is crucial for adequate innate and acquired immune responses to genital herpes simplex virus type 2 (HSV-2) infection in mice. To test the possible genetic influence of variations in the TBX21 gene encoding T-bet on susceptibility to infection, this study evaluated the frequencies of five different single-nucleotide polymorphisms (SNPs) in the human TBX21 gene in 159 HSV-2-infected individuals and compared them with those in 186 healthy HSV-2-seronegative controls. The data showed that one variation (rs17244587) in the 3'-untranslated region of TBX21 was strongly associated with the incidence of genital HSV-2 infection. The frequency of the A allele at this position was 0.19 in the group of HSV-2-infected individuals compared with 0.05 in the group of uninfected controls (P=9.3x10(-8)). Furthermore, a homozygous AA genotype was found only among HSV-2-infected individuals and not in seronegative controls. These results indicate that the host genetic background may affect susceptibility to HSV-2 infection in humans, with TBX21 as a strong candidate gene.
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| 20. |
- Svensson, Alexandra, 1978, et al.
(författare)
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Polymorphisms in Toll-like receptor 3 confer natural resistance to human herpes simplex virus type 2 infection.
- 2012
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 93:Pt 8, s. 1717-24
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Tidskriftsartikel (refereegranskat)abstract
- Lack of Toll-like receptor 3 (TLR3) functional activity predisposes children to human herpesvirus 1 (HSV-1) encephalitis. In this study, we have investigated whether there is any link between TLR3 and adult HSV-2 infection by studying genetic variations in TLR3. The frequency of four single-nucleotide polymorphisms (SNPs) in the TLR3 gene in 239 patients with genital HSV-2 infection and 162 healthy controls, as well as the impact of these variants on TLR3 gene-expression levels, were compared. Two SNPs in the TLR3 gene (rs13126816 and rs3775291) were associated with a reduced incidence of HSV-2 infection. The minor allelic variants at both rs13126816 and rs3775291 were more common among healthy HSV-2-seronegative subjects than among HSV-2-infected individuals. This was even more apparent in HSV-1-seronegative individuals. There was, however, no association between any of the four TLR3 SNPs and HSV-2 disease severity, as they were expressed at similar proportions in asymptomatic and symptomatic HSV-2-infected patients alike. Furthermore, when assessing TLR3 mRNA expression in a limited number of HSV-2-infected individuals, we found that individuals carrying the homozygous genotypes for the minor alleles had significantly higher levels of TLR3 mRNA expression in peripheral blood mononuclear cells in response to HSV-2 stimulation than individuals that were homozygous for the major allele variants. Taken together, these results suggest that genetic variations in TLR3 may affect the susceptibility to HSV-2 infection in humans.
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| 21. |
- Svensson, Alexandra, 1978, et al.
(författare)
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STAT4 Regulates Antiviral Gamma Interferon Responses and Recurrent Disease during Herpes Simplex Virus 2 Infection.
- 2012
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Ingår i: Journal of virology. - 1098-5514. ; 86:17, s. 9409-15
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Tidskriftsartikel (refereegranskat)abstract
- STAT4 is an important transcription factor that contributes to the incidence and severity of different autoimmune diseases and is implicated in the antiviral immune responses in mice. In this study, we evaluated the role of STAT4 in human and murine herpes simplex virus 2 (HSV-2) infections. We show that STAT4 regulates antiviral gamma interferon (IFN-γ) responses and disease severity during chronic HSV-2 infections in humans and vaccine-induced IFN-γ-mediated protection against HSV-2 infection in mice. In a cohort of 228 HSV-2-infected individuals, representing both patients with recurrent disease and asymptomatic HSV-2 carriers, we found that genetic variations in the STAT4 gene were associated with asymptomatic HSV-2 infection, as well as with increased in vitro secretion of IFN-γ in response to the virus. Mice that lacked STAT4 had impaired HSV-2-specific IFN-γ production and delayed-type hypersensitivity responses following vaccination, which led to impaired viral clearance in the genital tract of vaccinated animals after a genital HSV-2 challenge. We conclude that STAT4 plays an important role in IFN-γ-mediated HSV-2-specific immunity, affecting the severity of genital HSV-2 infection.
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| 22. |
- Tunbäck, Petra, 1965, et al.
(författare)
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Early acquisition of herpes simplex virus type 1 antibodies in children--a longitudinal serological study.
- 2007
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Ingår i: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. - : Elsevier BV. - 1386-6532. ; 40:1, s. 26-30
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Herpes simplex virus type 1 (HSV-1) infections are commonly acquired in childhood, asymptomatically or as a symptomatic infection. However, little is known about the time of HSV seroconversion during infancy and early childhood. OBJECTIVE: To investigate the acquisition of IgG-antibodies to HSV in infants and children. STUDY DESIGN: A longitudinal study, using type-specific HSV-1 and herpes simplex virus type 2 (HSV-2) enzyme-linked immunosorbent assays on sera collected from the mother and from their child at the age of 3, 5, 6, 12, 13 and 30 months. RESULTS: The maternal seroprevalences for HSV-1 was 65% and for HSV-2 19%. A gradual loss of maternal antibodies was seen, with few infants having detectable HSV-1 antibodies at the age of 1 year. A more rapid decline was registered for HSV-2 antibodies. A small number of new HSV-1 infections occurred in 3-5-month olds and more than half of the new infections were detected before the age of 13 months. At the age of 30 months, 30% of the children were HSV-1 antibody positive. CONCLUSION: Seroconversion to HSV-1 commonly occurs already during infancy, suggesting that HSV-1 is transmitted primarily from parent to child.
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| 23. |
- 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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| 24. |
- 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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| 25. |
- 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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| 26. |
- Tunbäck, Petra, 1965, et al.
(författare)
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Type-specific reactivity of anti-glycoprotein G antibodies from herpes simplex virus-infected individuals is maintained by single or dual type-specific residues.
- 2005
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 86:Pt 2, s. 247-51
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Forskningsöversikt (refereegranskat)abstract
- Glycoprotein G-1 (gG-1) of herpes simplex virus type 1 (HSV-1) and gG-2 of HSV-2 are the only known HSV proteins that induce type-specific human antibody responses. Recently, it was shown that purified human anti-gG-1 and anti-gG-2 antibodies presented a type-specific reactivity to immunogenic stretches with high similarity between gG-1 and gG-2. In this study, the molecular basis for this type-specific recognition was investigated employing synthetic peptides covering the indicated regions, including substitutions of the type-specific residues. The results revealed that single or dual type-specific residues localized within regions of high similarity could induce significant structural differences, explaining the type-specific recognition of the human antibody response to the gG proteins.
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