Role of interleukin-8 and transforming growth factor-β1 in enhancement of human cytomegalovirus replication by human T cell leukemia-lymphoma virus type I in macrophages coinfected with both viruses

Judit Szabó, Attila Bácsi, Zoltán Beck, Jolán Kiss, István Andirkó, Ferenc D. Tóth

Research output: Article

2 Citations (Scopus)

Abstract

Human cytomegalovirus (HCMV) is one of the most frequent opportunistic agents causing severe illness in chronic human T cell leukemia-lymphoma virus type I (HTLV-I) infection. Our previous studies have shown that coinfection of macrophages with HCMV and HTLV-I significantly enhances HCMV replication, resulting in release of infectious HCMV from dually infected cells. We found that double infection of macrophages with HCMV and HTLV-I induced a rapid production of substantial amounts of interleukin-8 (IL-8) and transforming growth factor-β1 (TGF-β1). Results of transfection studies demonstrated that the tax gene product of HTLV-I was able to induce secretion of IL-8 and TGF-β1. In addition to its cytokine-inducing effect, the Tax protein could interact with HCMV synergistically to result in production of much higher levels of IL-8 and TGF-β1 than expected on the basis of their separate activities. Treatment of dually infected macrophage cultures with neutralizing antibodies to IL-8 and TGF-β1 led to a nearly 1000-fold decrease in release of infectious HCMV from coinfected cells. Similar results were obtained when anti-IL-8 and anti-TGF-β1 treatments were combined in macrophage cultures transfected with the tax gene before HCMV infection. Our results suggest that the stimulatory effect of HTLV-I Tax protein on HCMV replication in coinfected macrophages is largely mediated by high levels of IL-8 and TGF-β1 production.

Original languageEnglish
Pages (from-to)209-217
Number of pages9
JournalJournal of Interferon and Cytokine Research
Volume19
Issue number2
DOIs
Publication statusPublished - márc. 11 1999

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ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

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