Related Experiment Video

Updated: Jan 29, 2026

Establishment and Quantification of De Novo Lytic Infection by Cell-free Kaposi's Sarcoma-Associated Herpesvirus
07:10

Establishment and Quantification of De Novo Lytic Infection by Cell-free Kaposi's Sarcoma-Associated Herpesvirus

Published on: August 15, 2025

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Human IFIT proteins inhibit lytic replication of KSHV: A new feed-forward loop in the innate immune system

Dajiang Li1, Sankar Swaminathan1,2

  • 1Division of Infectious Diseases, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.

Plos Pathogens
|February 20, 2019
PubMed

Insights

The Interferon-induced proteins with tetratricp repeats (IFITs) inhibit Kaposi

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease.
  • The role of Interferon-induced proteins with tetratricp repeats (IFITs) in KSHV lytic replication was previously unknown.

Purpose of the Study:

  • To investigate the effect of IFIT proteins on KSHV lytic replication.
  • To elucidate the mechanisms by which IFITs might regulate KSHV replication.

Main Methods:

  • Depletion of IFIT1, IFIT2, and IFIT3 (IFITs) in KSHV-infected epithelial cells.
  • Quantification of infectious KSHV virion production and intracellular viral genomes.
  • RNA sequencing (RNA-seq) to analyze gene expression changes, including interferon-stimulated genes (ISGs).
  • Immunoprecipitation assays to assess IFIT1 binding to viral and cellular mRNAs.

Main Results:

  • IFIT depletion significantly increased infectious KSHV virion production (25-32 fold) and intracellular viral DNA.
  • KSHV lytic gene expression was broadly upregulated upon IFIT knockdown.
  • IFIT depletion led to downregulation of Interferon beta (IFN β) and downstream ISGs, including OAS proteins, reducing RNase L activity.
  • IFIT1 directly binds to viral and cellular capped mRNAs, suggesting a role in inhibiting viral mRNA expression.

Conclusions:

  • IFIT proteins inhibit KSHV lytic replication.
  • IFITs exert their inhibitory effect by upregulating the IFN β and OAS-RNase L pathway, promoting RNA degradation.
  • IFITs may also directly target and inhibit viral mRNA expression through binding.

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