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Role of interleukin-8 and transforming growth factor-beta1 in enhancement of human cytomegalovirus replication by human T cell leukemia-lymphoma virus type I in macrophages coinfected with both viruses.




 

J Interferon Cytokine Res. 1999 Feb;19(2):209-17. Unique Identifier :

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-beta1 (TGF-beta1). Results of transfection studies demonstrated that the tax gene product of HTLV-I was able to induce secretion of IL-8 and TGF-beta1. 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-beta1 than expected on the basis of their separate activities. Treatment of dually infected macrophage cultures with neutralizing antibodies to IL-8 and TGF-beta1 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-beta1 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-beta1 production.

JOURNAL ARTICLE Antibodies, Monoclonal Cell Line Cytomegalovirus Infections/METABOLISM/*PHYSIOPATHOLOGY Gene Products, tax/IMMUNOLOGY Human HTLV-I Infections/METABOLISM/*PHYSIOPATHOLOGY Interleukin-8/BIOSYNTHESIS/*PHYSIOLOGY Macrophages/*PHYSIOLOGY Support, Non-U.S. Gov't Transforming Growth Factor beta/BIOSYNTHESIS/*PHYSIOLOGY *Virus Replication



 




Information in this article was accurate in July 30, 1999. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.