Runaway Kaposi Sarcoma-associated herpesvirus replication correlates with systemic IL-10 levels

Virology. 2020 Jan 2:539:18-25. doi: 10.1016/j.virol.2019.10.002. Epub 2019 Oct 2.

Abstract

KSHV-associated inflammatory cytokine syndrome (KICS) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV). KICS is associated with high-level, systemic replication of KSHV. This study characterized the clinical and virologic features of a KICS patient over time. Additionally, it compared the cytokine profiles of the KICS case to Kaposi's sarcoma (KS) (n = 11) and non-KS (n = 6) cases. This KICS case presented with elevated levels of KSHV and IL-10, as expected. Surprisingly, this case did not have elevated levels of IL-6 or human immunodeficiency virus 1 (HIV-1). Nevertheless, treatment with anti-IL6 receptor antibody (tocilizumab) reduced KSHV viral load and IL-10. The KSHV genome sequence showed no significant changes over time, except in ORF24. Phylogenetic analysis established this isolate as belonging to KSHV clade A and closely related to other US isolates. These findings suggest IL-10 as potential biomarker and therapy target for KICS.

Keywords: Castleman's disease; Herpesvirus; IRIS; KICS; KSHV; Kaposi's sarcoma; Tocilizumab.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy
  • AIDS-Related Opportunistic Infections / immunology
  • AIDS-Related Opportunistic Infections / virology
  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Biomarkers / blood
  • Cytokine Release Syndrome
  • DNA, Viral / blood
  • DNA, Viral / genetics
  • Genome, Viral / genetics
  • Herpesviridae Infections / diagnosis
  • Herpesviridae Infections / drug therapy
  • Herpesviridae Infections / immunology*
  • Herpesviridae Infections / virology*
  • Herpesvirus 8, Human / classification
  • Herpesvirus 8, Human / genetics
  • Herpesvirus 8, Human / isolation & purification
  • Herpesvirus 8, Human / physiology*
  • Humans
  • Interleukin-10 / blood*
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Phylogeny
  • Sarcoma, Kaposi / immunology
  • Sarcoma, Kaposi / virology
  • Viral Load
  • Virus Replication / immunology*

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • DNA, Viral
  • IL10 protein, human
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-10
  • tocilizumab