Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Inefficient establishment of KSHV latency suggests an additional role for continued lytic replication in Kaposi sarcoma pathogenesis
Adam Grundhoff, Don Ganem
Adam Grundhoff, Don Ganem
Published January 1, 2004
Citation Information: J Clin Invest. 2004;113(1):124-136. https://doi.org/10.1172/JCI17803.
View: Text | PDF
Article Infectious disease

Inefficient establishment of KSHV latency suggests an additional role for continued lytic replication in Kaposi sarcoma pathogenesis

  • Text
  • PDF
Abstract

Kaposi sarcoma–associated (KS-associated) herpesvirus (KSHV) infection is linked to the development of both KS and several lymphoproliferative diseases. In all cases, the resulting tumor cells predominantly display latent viral infection. KS tumorigenesis requires ongoing lytic viral replication as well, however, for reasons that are unclear but have been suggested to involve the production of angiogenic or mitogenic factors by lytically infected cells. Here we demonstrate that proliferating cells infected with KSHV in vitro display a marked propensity to segregate latent viral genomes, with only a variable but small subpopulation being capable of stable episome maintenance. Stable maintenance is not due to the enhanced production of viral or host trans-acting factors, but is associated with cis-acting, epigenetic changes in the viral chromosome. These results indicate that acquisition of stable KSHV latency is a multistep process that proceeds with varying degrees of efficiency in different cell types. They also suggest an additional role for lytic replication in sustaining KS tumorigenesis: namely, the recruitment of new cells to latency to replace those that have segregated the viral episome.

Authors

Adam Grundhoff, Don Ganem

×

Figure 7

Options: View larger image (or click on image) Download as PowerPoint
Analysis of SLKP and SLKN cells. (a) SLKN cells were infected with viral...
Analysis of SLKP and SLKN cells. (a) SLKN cells were infected with viral supernatants from lytically induced BCBL-1 cells. The percentage of LANA-positive cells was evaluated over a period of 40 days by IFA (solid line). The curve obtained from the initial infection of the parental SLK mass cultures (see Figure 4) is shown for comparison (dashed line). (b) SLKN (open circles) or SLKP cells (filled squares) were infected with recombinant KSHV-GFP supernatants, and the percentage of GFP-positive cells was analyzed by FACS over a period of 3 weeks. Shown are normalized percentages relative to the initial infection level (absolute infection efficiencies were 2.9% and 4.2% for SLKN and SLKP cells, respectively). (c) SLKN cells (solid lines, filled symbols) or uninfected SLK cells (dashed lines, open symbols) were transfected with the reporter constructs pGFP (circles), pGTR4 (squares), or pGTR4:73 (triangles). The percentage of GFP-expressing cells was monitored over a period of 17 days after transfection by FACS. (d) SLKP cells were transfected with pGFP (circles) or pGTR4 (squares) and analyzed by FACS over a period of 17 days. (e) PCR analysis of the transfected SLK, SLKN, and SLKP cultures described above. Episomal DNA was isolated at the time points indicated (in days) above the lanes by Hirt extraction and subjected to PCR amplification of the GFP cassette as described in Methods.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts