Efficient lytic induction of Kaposi's sarcoma-associated herpesvirus (KSHV) by the anthracyclines

Hyunju Kang1, Jaehyung Song2, Kwangman Choi3

  • 1Targeted Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon, Chungbuk, Republic of Korea. College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.

Oncotarget
|September 20, 2014
PubMed

Insights

Three FDA-approved anthracyclines were identified as potent inducers of Kaposi

Area of Science:

  • Virology
  • Oncology
  • Drug Discovery

Background:

  • Latent Kaposi's sarcoma-associated herpesvirus (KSHV) infection is linked to several malignancies.
  • Lytic induction of KSHV is a potential therapeutic strategy for KSHV-associated diseases.
  • Existing KSHV lytic induction methods require optimization for efficiency and scalability.

Purpose of the Study:

  • To develop a high-throughput screening system for quantifying KSHV lytic induction.
  • To identify FDA-approved drugs capable of inducing KSHV lytic replication.
  • To elucidate the mechanism of KSHV lytic induction by identified compounds.

Main Methods:

  • Development of a robust, quantitative high-throughput screening assay for KSHV lytic induction.
  • Screening of FDA-approved drug libraries to identify novel KSHV inducers.
  • Verification of lytic gene induction and infectious KSHV production.
  • Mechanistic studies involving apoptosis and DNA intercalation assays.

Main Results:

  • Three anthracycline compounds were identified as potent inducers of KSHV lytic replication.
  • Lytic induction by these anthracyclines significantly exceeded that of sodium butyrate.
  • Anthracyclines induced KSHV lytic replication via apoptosis mediated by DNA intercalation.
  • Infectious KSHV production was confirmed following anthracycline treatment.

Conclusions:

  • Anthracyclines are effective inducers of KSHV lytic replication.
  • The identified compounds offer a promising therapeutic avenue for KSHV-associated diseases.
  • Understanding the mechanism provides a basis for targeted KSHV therapies.

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