| 1. |
- Bissett, Sara L., et al.
(författare)
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Human Papillomavirus Antibody Reference Reagents for Use in Postvaccination Surveillance Serology
- 2012
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Ingår i: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 19:3, s. 449-451
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Tidskriftsartikel (refereegranskat)abstract
- Suitably controlled serosurveillance surveys are essential for evaluating human papillomavirus (HPV) immunization programs. A panel of plasma samples from 18-year-old females was assembled, the majority of the samples being from recipients of the bivalent HPV vaccine. Antibody specificities were evaluated by three independent laboratories, and 3 pools that displayed no antibodies to any HPV type tested or intermediate or high levels of antibody to HPV16, HPV18, HPV31, and HPV45 were created. These pools will be useful as control reagents for HPV serology.
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| 2. |
- Bzhalava, Davit, et al.
(författare)
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Phylogenetically diverse TT virus viremia among pregnant women
- 2012
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Ingår i: Virology. - : Elsevier BV. - 1096-0341 .- 0042-6822. ; 432:2, s. 427-434
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Tidskriftsartikel (refereegranskat)abstract
- Infections during pregnancy have been suggested to be involved in childhood leukemias. We used high-throughput sequencing to describe the viruses most readily detectable in serum samples of pregnant women. Serum DNA of 112 mothers to leukemic children was amplified using whole genome amplification. Sequencing identified one TT virus (TTV) isolate belonging to a known type and two putatively new TTVs. For 22 mothers, we also performed ITV amplification by general primer PCR before sequencing. This detected 39 TTVs, two of which were identical to the Tilts found after whole genome amplification. Altogether, we found 40 TTV isolates, 29 of which were putatively new types (similarities ranging from 89% to 69%). In conclusion, high throughput sequencing is useful to describe the known or unknown viruses that are present in serum samples of pregnant women. (C) 2012 Elsevier Inc. All rights reserved.
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| 3. |
- Bzhalava, Davit, et al.
(författare)
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Unbiased Approach for Virus Detection in Skin Lesions
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- To assess presence of virus DNA in skin lesions, swab samples from 82 squamous cell carcinomas of the skin (SCCs), 60 actinic keratoses (AKs), paraffin-embedded biopsies from 28 SCCs and 72 kerathoacanthomas (KAs) and fresh-frozen biopsies from 92 KAs, 85 SCCs and 92 AKs were analyzed by high throughput sequencing (HTS) using 454 or Ion Torrent technology. We found total of 4,284 viral reads, out of which 4,168 were Human Papillomavirus (HPV)-related, belonging to 15 known (HPV8, HPV12, HPV20, HPV36, HPV38, HPV45, HPV57, HPV59, HPV104, HPV105, HPV107, HPV109, HPV124, HPV138, HPV147), four previously described putative (HPV 915 F 06 007 FD1, FA73, FA101, SE42) and two putatively new HPV types (SE46, SE47). SE42 was cloned, sequenced, designated as HPV155 and found to have 76% similarity to the most closely related known HPV type. In conclusion, an unbiased approach for viral DNA detection in skin tumors has found that, although some new putative HPVs were found, known HPV types constituted most of the viral DNA.
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| 4. |
- Faust, Helena, et al.
(författare)
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Antibodies to merkel cell polyomavirus correlate to presence of viral DNA in the skin.
- 2011
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 203:8, s. 1096-1100
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Tidskriftsartikel (refereegranskat)abstract
- To validate whether Merkel cell polyomavirus (MCV) serology correlates with MCV infection, we compared real-time polymerase chain reaction results for MCV DNA on fresh-frozen biopsy specimens from various skin lesions and healthy skin from 434 patients to MCV serology results using viruslike particles (VLPs) and MCV neutralization assays. Sixty-five percent of participants were MCV seropositive and 18% were MCV DNA positive. The presence of antibodies was correlated with the presence of virus DNA (odds ratio, 27.85 [95% confidence interval, 6.6-166.5]), with 97% of patients who tested positive for MCV DNA being MCV seropositive. VLP antibody levels correlated to neutralization titers (r = .72), and high antibody levels correlated to high MCV load (P < .01).
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| 5. |
- Faust, Helena, et al.
(författare)
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Cutaneous Human Papillomaviruses and squamous cell carcinoma of the skin: Nested case-control study.
- 2016
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Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1538-7755.
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Tidskriftsartikel (refereegranskat)abstract
- Cutaneous Human Papillomavirus (HPV) types have been associated with non-melanoma skin cancer (NMSC), including a previous nested case-control study using HPV serology with bacterially derived fusion proteins with the major HPV capsid protein L1 (GST-L1). However, HPV serology using conformationally intact pseudovirions has been shown to correlate better with natural infection. Prospective studies using a more valid marker of infection are therefore warranted.
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| 6. |
- Faust, Helena, et al.
(författare)
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Human Papillomavirus neutralizing and cross-reactive antibodies induced in HIV-positive subjects after vaccination with quadrivalent and bivalent HPV vaccines.
- 2016
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; , s. 1559-1559
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Tidskriftsartikel (refereegranskat)abstract
- Ninety-one HIV-infected individuals (61 men and 30 women) were randomized to vaccination either with quadrivalent (Gardasil™) or bivalent (Cervarix™) HPV vaccine. Neutralizing and specific HPV-binding serum antibodies were measured at baseline and 12 months after the first vaccine dose. Presence of neutralizing and binding antibodies had good agreement (average Kappa for HPV types 6, 11, 16, 18, 31, 33 and 45 was 0.65). At baseline, 88% of subjects had antibodies against at least one genital HPV. Following vaccination with Cervarix™, all subjects became seropositive for HPV16 and 18. After Gardasil™ vaccination, 96% of subjects seroconverted for HPV16 and 73% for HPV18. Levels of HPV16-specific antibodies were <1 international unit (IU) in 87% of study subjects before vaccination but >10IU in 85% of study subjects after vaccination. Antibodies against non-vaccine HPV types appeared after Gardasil™ vaccination for >50% of vaccinated females for HPV 31, 35 and 73 and for >50% of Cervarix™-vaccinated females for HPV 31, 33, 35, 45, 56 and 58. Cross-reactivity with non-genital HPV types was also detected. In conclusion, HIV-infected subjects responded to HPV vaccination with induction of neutralizing antibodies against both vaccine and non-vaccine types.
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| 7. |
- Faust, Helena, et al.
(författare)
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Mutations in human papillomavirus type 16 L1 hypervariable surface-exposed loops affect L2 binding and DNA encapsidation
- 2013
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 94:Pt 8, s. 1841-1849
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Tidskriftsartikel (refereegranskat)abstract
- Prophylactic vaccines against human papillomavirus (HPV) based on virus-like particles (VLP) induce type-specific neutralizing antibodies against a small number of hypervariable residues positioned in surface-exposed loops of the major capsid protein L1. To investigate the importance of these residues for neutralization, cross-neutralization, L2 incorporation and genome encapsidation, ten surface-exposed amino acid residues in four hypervariable loops of L1 were mutated. VLPs containing mutated or WT L1, with or without WT L2, were produced in 293TT cells using pseudovirion expression vectors. The mutations reduced the ability to induce neutralizing antibodies and to incorporate the L2 protein in the capsid. Ability to induce cross-neutralizing antibodies and to encapsidate pseudogenomes were completely abrogated. In summary, the surface-exposed L1 loops are important for the function of the HPV particle.
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| 8. |
- Faust, Helena, et al.
(författare)
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Prevalence of human papillomavirus types, viral load and physical status of HPV16 in head and neck squamous cell carcinoma from the South Swedish Health Care Region
- 2016
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 97:11, s. 2949-2956
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Tidskriftsartikel (refereegranskat)abstract
- Incidence of human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is rising in several countries. Intriguingly, large variations of HPV16 viral load and different proportions of the physical viral status among HNSCC have been reported. We analysed fresh biopsies of 275 HNSCC patients from the South Swedish Health Care Region for HPV types with modified general primer PCR and Luminex. Seventy-eight HPV16-positive HNSCC cases were further investigated for viral DNA load and physical status using quantitative PCR for HPV E2 and E7 genes. Presence of intact E2 gene, as a surrogate marker for episomal HPV, was investigated with conventional PCR. Fifteen different HPV types were detected in HNSCC cases and HPV16 was present in 74% of the HPV-positive cases. HPV was detected in 65% (92/141) and 11% (15/134) of oropharyngeal and non-oropharyngeal carcinomas, respectively (P<0.0001). HPV was detected in 73% (75/103) of tonsillar carcinomas. The median load of HPV16 was 13 copies cell-1 (range 0.003–1080). Among HPV16-positive patients with oropharyngeal carcinoma, metastases to regional lymph nodes were observed in 100% (17/17) and 68% (40/58) for those with <1 HPV16 copy cell-1 and >1 HPV16 copy Cell-1, respectively (P=0.007). Among HPV16 cases, purely integrated HPV16 was found in 6%, whereas entirely episomal and mixed virus was detected in 51 and 42% of cases, respectively. Conclusively, HPV16 viral DNA load demonstrated a large diversity among HNSCCs. Although integration of HPV16 is common (48%), the episomal HPV16 is salient (93%) among HPV16 HNSCCs. In addition, low amount of HPV16 was associated with lymph node metastases among oropharyngeal carcinomas.
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| 9. |
- Faust, Helena, et al.
(författare)
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Prospective study of merkel cell polyomavirus and risk of merkel cell carcinoma.
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:4, s. 844-848
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Tidskriftsartikel (refereegranskat)abstract
- Merkel cell carcinoma (MCC) is a rare type of skin cancer that has a characteristically increased incidence among immunosuppressed subjects. The DNA of Merkel cell polyomavirus (MCV) is regularly found in most MCC tumors. We investigated whether Merkel cell polyomavirus (MCV) infection increases the risk for future Merkel cell carcinoma (MCC). Two large biobank cohorts (Southern Sweden Microbiology Biobank and the Janus Biobank), containing samples from 856,000 healthy donors, were linked to the Cancer Registries in Sweden and Norway to identify cases of MCC occurring up to 30 years after donation of a serum sample. For each of the 22 cases (9 males and 13 females), four matched controls were included. The serum samples were analysed with an MCV neutralization assay and for IgG antibodies to MCV pseudovirions, using JC polyomavirus and cutaneous Human papillomaviruses as control antigens. An increased risk for future MCC was associated both with high levels of MCV antibodies (OR 4.4, 95% CI 1.3-17.4) and with MCV neutralizing activity (OR 5.3, 95% CI 1.3-32.3). In males, MCV seropositivity was not associated to MCC risk, whereas the risk was strongly increased in females, both for high levels of MCV antibodies (OR 7.0, 95% CI 1.6-42.8) and for MCV neutralizing activity (OR 14.3, 95% CI 1.7-677). In conclusion, we found prospective evidence that MCV infection is associated with an increased risk for future MCC, in particular among females. © 2013 Wiley Periodicals, Inc.
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| 10. |
- Faust, Helena, et al.
(författare)
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Pseudovirion-binding and neutralizing antibodies to cutaneous Human Papillomaviruses correlated to presence of HPV DNA in skin.
- 2013
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Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 94, s. 1096-1103
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Tidskriftsartikel (refereegranskat)abstract
- We compared seroreactivity to Human papillomavirus (HPV) antigens measured with two different high-throughput assays. One method used GST-L1 fusion proteins and the other heparin-bound HPV pseudovirions as antigens and both methods used multiplexed fluorescent beads for detection. For six HPV types (5, 6, 15, 16, 32 and 38), seroreactivity could be measured in parallel for 434 serum samples from non-immunosuppressed patients with skin lesions (squamous cell carcinoma of the skin, basal cell carcinoma of the skin, actinic keratosis and benign skin lesions). Biopsies from the skin lesions were tested for presence of HPV DNA using three different PCR methods, with typing by sequencing. Among the types included in the serological tests, HPV DNA of types HPV5, 15, 38 and 76 were most frequently detected in the tumours. Serum samples from subjects with HPV DNA positive biopsies and randomly selected serum samples from subjects with HPV DNA negative biopsies were also tested with neutralization assays with HPV5, 38 and 76 pseudovirions. Agreement of the three serological methods varied from poor to moderate and showed limited consistency. Type-specific seroprevalences among patients positive for the same type of HPV DNA (sensitivity of serology) was improved with the pseudovirion-based method (average of 40%, maximum 63%) compared to the GST-L1 method (average of 20%, maximum of 25%). Neutralization was the most sensitive assay for HPV38 (50%). In summary, the pseudovirion-based methods appeared to have an improved sensitivity.
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