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.
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.
Szabó
J
J
Institute of Microbiology, University Medical School, Debrecen, Hungary.
Bácsi
A
A
Beck
Z
Z
Kiss
J
J
Andirkó
I
I
Tóth
F D
FD
D000911:Antibodies, Monoclonal; D002460:Cell Line; D003586:Cytomegalovirus Infections / Q000378:metabolism / Q000503:physiopathology*; D016356:Gene Products, tax / Q000276:immunology; D015490:HTLV-I Infections / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000502:physiology*; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D016356:Gene Products, tax; D016209:Interleukin-8; D016212:Transforming Growth Factor beta