Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma

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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.

Original languageEnglish
Article number35
JournalInfectious Agents and Cancer
Volume12
Issue number1
DOIs
Publication statusPublished - Jun 19 2017

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Electrochemotherapy
Human Herpesvirus 8
Kaposi's Sarcoma
Blood Cells
Viral Load
Biopsy
Therapeutics
Messenger RNA
DNA
Real-Time Polymerase Chain Reaction
Nucleotides

Keywords

  • Electrochemotherapy
  • HHV8
  • K1
  • Kaposi sarcoma
  • ORF26
  • Viral load

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Cancer Research
  • Infectious Diseases

Cite this

@article{1bdbcca0f73b498289319087d4bfcd11,
title = "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 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.",
keywords = "Electrochemotherapy, HHV8, K1, Kaposi sarcoma, ORF26, Viral load",
author = "Noemy Starita and {Di Monta}, Gianluca and Andrea Cerasuolo and Ugo Marone and Anniciello, {Anna Maria} and Gerardo Botti and Luigi Buonaguro and Buonaguro, {Franco M.} and Tornesello, {Maria Lina}",
year = "2017",
month = "6",
day = "19",
doi = "10.1186/s13027-017-0147-4",
language = "English",
volume = "12",
journal = "Infectious Agents and Cancer",
issn = "1750-9378",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma

AU - Starita, Noemy

AU - Di Monta, Gianluca

AU - Cerasuolo, Andrea

AU - Marone, Ugo

AU - Anniciello, Anna Maria

AU - Botti, Gerardo

AU - Buonaguro, Luigi

AU - Buonaguro, Franco M.

AU - Tornesello, Maria Lina

PY - 2017/6/19

Y1 - 2017/6/19

N2 - 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.

AB - 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.

KW - Electrochemotherapy

KW - HHV8

KW - K1

KW - Kaposi sarcoma

KW - ORF26

KW - Viral load

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U2 - 10.1186/s13027-017-0147-4

DO - 10.1186/s13027-017-0147-4

M3 - Article

AN - SCOPUS:85020942526

VL - 12

JO - Infectious Agents and Cancer

JF - Infectious Agents and Cancer

SN - 1750-9378

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