Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma
Abstract Background Electrochemotherapy (ECT) has shown to be an effective treatment for cutaneous and subcutaneous Kaposi sarcoma (KS) lesions. However, no study has investigated the impact of ECT treatment on the kinetics of human herpesvirus type 8 (HHV8), which is considered the necessary causal...
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | Infectious Agents and Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s13027-017-0147-4 |
| _version_ | 1818619562927587328 |
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| author | Noemy Starita Gianluca Di Monta Andrea Cerasuolo Ugo Marone Anna Maria Anniciello Gerardo Botti Luigi Buonaguro Franco M. Buonaguro Maria Lina Tornesello |
| author_facet | Noemy Starita Gianluca Di Monta Andrea Cerasuolo Ugo Marone Anna Maria Anniciello Gerardo Botti Luigi Buonaguro Franco M. Buonaguro Maria Lina Tornesello |
| author_sort | Noemy Starita |
| collection | DOAJ |
| description | Abstract Background Electrochemotherapy (ECT) has shown to be an effective treatment for cutaneous and subcutaneous Kaposi sarcoma (KS) lesions. However, no study has investigated the impact of ECT treatment on the kinetics of human herpesvirus type 8 (HHV8), which is considered the necessary causal agent of KS. We aimed to evaluate HHV8 viral load and expression levels in patients affected by classic KS who received one or more ECT treatments and have been followed semi annually for up to four years. Methods A total of 27 classic KS patients were enrolled in this study. Tumour biopsies and blood samples were obtained before ECT treatment. Additional blood samples were collected at six month intervals for 12–48 months. HHV8 viral load and expression profiles of latent (ORF72 and ORF73) and lytic (K2, K8, K8.1, K10/K10.1, K10.5/K10.6 and ORF16) genes were assessed in all samples by real-time PCR. HHV8 ORF26 and K1 regions were amplified and subjected to direct nucleotide sequencing followed by phylogenetic analysis for variant identification. Results All KS biopsies and 46.4% of peripheral blood mononuclear cells (PBMCs) collected before ECT treatment were positive for HHV8 DNA. Viral load ranged from 0.02 to 2.3 copies per cell in KS lesions and 3.0 × 10−7 to 6.9 × 10−4 copies per cell in PBMCs. Overall, latent ORF72 and ORF73 as well as lytic K2, K8 and K10/K10.1 were expressed in all KS biopsies. ORF16 mRNA was detected in 71.4% and both K8.1 and K10.5/K10.6 mRNAs in 57.1% of KS samples. The ORF72, ORF73 and K2 transcripts were amplified in 37.5%, 25% and 25% of PBMCs collected before ECT, respectively. After the first ECT session, complete response was achieved in 20 out of 27 (74.1%) patients and HHV8 DNA was detected in four out of 27 (14.8%) PBMC samples at six month follow up. Phylogenetic analysis of ORF26 amplimers showed that most viral variants belonged to A/C (82.3%), and few to C2 (5.9%) or C3 (11.8%) subtype. The K1/VR1 variants fell into A (33.3%) and C (66.7%) HHV8 clade. No correlation was found between HHV8 subtypes and ECT complete response. Conclusions ECT therapy has a significant effect on HHV8 kinetics in patients with classic KS. The complete remission of patients was accompanied by clearance of circulating virus. |
| first_indexed | 2024-12-16T17:39:28Z |
| format | Article |
| id | doaj.art-bc1bc3c7431344989386b44a31f8e2ef |
| institution | Directory Open Access Journal |
| issn | 1750-9378 |
| language | English |
| last_indexed | 2024-12-16T17:39:28Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
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| series | Infectious Agents and Cancer |
| spelling | doaj.art-bc1bc3c7431344989386b44a31f8e2ef2022-12-21T22:22:39ZengBMCInfectious Agents and Cancer1750-93782017-06-011211910.1186/s13027-017-0147-4Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcomaNoemy Starita0Gianluca Di Monta1Andrea Cerasuolo2Ugo Marone3Anna Maria Anniciello4Gerardo Botti5Luigi Buonaguro6Franco M. Buonaguro7Maria Lina Tornesello8Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS “Fond. G. Pascale”Department of Surgery “Melanoma, Soft Tissues, Head and Neck, Skin Cancers”, Istituto Nazionale Tumori IRCCS “Fond. G. Pascale”Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS “Fond. G. Pascale”Department of Surgery “Melanoma, Soft Tissues, Head and Neck, Skin Cancers”, Istituto Nazionale Tumori IRCCS “Fond. G. Pascale”Department of Pathology, Istituto Nazionale Tumori IRCCS “Fond. G. Pascale”Department of Pathology, Istituto Nazionale Tumori IRCCS “Fond. G. Pascale”Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS “Fond. G. Pascale”Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS “Fond. G. Pascale”Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori IRCCS “Fond. G. Pascale”Abstract Background Electrochemotherapy (ECT) has shown to be an effective treatment for cutaneous and subcutaneous Kaposi sarcoma (KS) lesions. However, no study has investigated the impact of ECT treatment on the kinetics of human herpesvirus type 8 (HHV8), which is considered the necessary causal agent of KS. We aimed to evaluate HHV8 viral load and expression levels in patients affected by classic KS who received one or more ECT treatments and have been followed semi annually for up to four years. Methods A total of 27 classic KS patients were enrolled in this study. Tumour biopsies and blood samples were obtained before ECT treatment. Additional blood samples were collected at six month intervals for 12–48 months. HHV8 viral load and expression profiles of latent (ORF72 and ORF73) and lytic (K2, K8, K8.1, K10/K10.1, K10.5/K10.6 and ORF16) genes were assessed in all samples by real-time PCR. HHV8 ORF26 and K1 regions were amplified and subjected to direct nucleotide sequencing followed by phylogenetic analysis for variant identification. Results All KS biopsies and 46.4% of peripheral blood mononuclear cells (PBMCs) collected before ECT treatment were positive for HHV8 DNA. Viral load ranged from 0.02 to 2.3 copies per cell in KS lesions and 3.0 × 10−7 to 6.9 × 10−4 copies per cell in PBMCs. Overall, latent ORF72 and ORF73 as well as lytic K2, K8 and K10/K10.1 were expressed in all KS biopsies. ORF16 mRNA was detected in 71.4% and both K8.1 and K10.5/K10.6 mRNAs in 57.1% of KS samples. The ORF72, ORF73 and K2 transcripts were amplified in 37.5%, 25% and 25% of PBMCs collected before ECT, respectively. After the first ECT session, complete response was achieved in 20 out of 27 (74.1%) patients and HHV8 DNA was detected in four out of 27 (14.8%) PBMC samples at six month follow up. Phylogenetic analysis of ORF26 amplimers showed that most viral variants belonged to A/C (82.3%), and few to C2 (5.9%) or C3 (11.8%) subtype. The K1/VR1 variants fell into A (33.3%) and C (66.7%) HHV8 clade. No correlation was found between HHV8 subtypes and ECT complete response. Conclusions ECT therapy has a significant effect on HHV8 kinetics in patients with classic KS. The complete remission of patients was accompanied by clearance of circulating virus.http://link.springer.com/article/10.1186/s13027-017-0147-4HHV8Kaposi sarcomaElectrochemotherapyViral loadORF26K1 |
| spellingShingle | Noemy Starita Gianluca Di Monta Andrea Cerasuolo Ugo Marone Anna Maria Anniciello Gerardo Botti Luigi Buonaguro Franco M. Buonaguro Maria Lina Tornesello Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma Infectious Agents and Cancer HHV8 Kaposi sarcoma Electrochemotherapy Viral load ORF26 K1 |
| title | Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma |
| title_full | Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma |
| title_fullStr | Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma |
| title_full_unstemmed | Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma |
| title_short | Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma |
| title_sort | effect of electrochemotherapy on human herpesvirus 8 kinetics in classic kaposi sarcoma |
| topic | HHV8 Kaposi sarcoma Electrochemotherapy Viral load ORF26 K1 |
| url | http://link.springer.com/article/10.1186/s13027-017-0147-4 |
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