| 1. |
- Bergström, Petra, et al.
(författare)
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Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons
- 2021
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Ingår i: Viruses-Basel. - : MDPI AG. - 1999-4915. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus 1 (HSV-1) and 2 (HSV-2) can infect the central nervous system (CNS) with dire consequences; in children and adults, HSV-1 may cause focal encephalitis, while HSV-2 causes meningitis. In neonates, both viruses can cause severe, disseminated CNS infections with high mortality rates. Here, we differentiated human induced pluripotent stem cells (iPSCs) towards cortical neurons for infection with clinical CNS strains of HSV-1 or HSV-2. Progenies from both viruses were produced at equal quantities in iPSCs, neuroprogenitors and cortical neurons. HSV-1 and HSV-2 decreased viability of neuroprogenitors by 36.0% and 57.6% (p < 0.0001), respectively, 48 h post-infection, while cortical neurons were resilient to infection by both viruses. However, in these functional neurons, both HSV-1 and HSV-2 decreased gene expression of two markers of synaptic activity, CAMK2B and ARC, and affected synaptic activity negatively in multielectrode array experiments. However, unaltered secretion levels of the neurodegeneration markers tau and NfL suggested intact axonal integrity. Viral replication of both viruses was found after six days, coinciding with 6-fold and 22-fold increase in gene expression of cellular RNA polymerase II by HSV-1 and HSV-2, respectively. Our results suggest a resilience of human cortical neurons relative to the replication of HSV-1 and HSV-2.
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| 2. |
- 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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| 3. |
- Franzen-Röhl, Elisabeth, et al.
(författare)
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Increased cell-mediated immune responses in patients with recurrent herpes simplex virus type 2 meningitis.
- 2011
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Ingår i: Clinical and vaccine immunology : CVI. - 1556-679X. ; 18:4, s. 655-60
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Tidskriftsartikel (refereegranskat)abstract
- The clinical picture of herpes simplex virus type 2 (HSV-2) infection includes genital blisters and less frequently meningitis, and some individuals suffer from recurrent episodes of these manifestations. We hypothesized that adaptive and/or innate immune functional deficiencies may be a major contributing factor in susceptibility to recurrent HSV-2 meningitis. Ten patients with recurrent HSV-2 meningitis were studied during clinical remission. For comparison, 10 patients with recurrent genital HSV infections as well as 21 HSV-seropositive and 19 HSV-seronegative healthy blood donors were included. HSV-specific T cell blasting and cytokine secretion were evaluated in whole blood cultures. HSV-2-induced NK cell gamma interferon production, dendritic cell Toll-like receptor (TLR) expression, and TLR agonist-induced alpha interferon secretion were analyzed. Patients with recurrent HSV-2 meningitis had elevated T cell blasting and Th1 and Th2 cytokine production in response to HSV antigens compared to those of patients with recurrent genital infections. A somewhat increased NK cell response, increased dendritic cell expression of TLR3 and -9, and increased TLR-induced alpha interferon responses were also noted. Contrary to our expectation, recurrent HSV-2 meningitis patients have increased HSV-specific adaptive and innate immune responses, raising the possibility of immune-mediated pathology in the development of recurrent HSV2 meningitis.
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| 4. |
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| 5. |
- 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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| 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. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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