HIV-1 Tat dysregulation of KSHV induced immune response through the production of IL-8

Abstract

Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS) and is a major health issue around the world. HIV is known to induce a number of pathological problems in AIDS patients via the transactivator (Tat) protein that is expressed and released by infected cells. One of the most important function of Tat is the dysregulation of the immune response. IL-8 is a chemokine known to be highly expressed in AIDS patients and Tat plays a major role in its production. IL-8 increases the HIV transmission and replication rate; and plays a role in Kaposi's sarcoma associated herpesvirus (KSHV) infection, which is a major opportunistic pathogen that AIDS patients are at risk to. KSHV is also known to induce the expression of IL-8 in patients, and IL-8 is known to assist tumour development by increasing angiogenesis. In our study, we investigated the role that Tat may have in manipulating the expression of IL-8 induced by KSHV in primary blood monocyte derived macrophages (PBMac). The results showed that pretreatment of PBMac with Tat inhibited the expression of IL-8 induced by KSHV by approximately 40%. We also found that Tat was able to inhibit the phosphorylation of STAT-1 induced by KSHV, and the inhibition of STAT-1 phosporylation was related to the expression of IL-8 induced by KSHV. In conclusion, we found that Tat was able to manipulate the expression of IL-8 induced by KSHV in macrophages, and this inhibition of IL-8 expression was regulated through the STAT-1 related pathways.