Spontaneous Production of C-C Chemokines by Individuals Infected with Human T Lymphotropic Virus Type II (HTLV-II) Alone and HTLV-II/HIV-1 Coinfected Individuals

Abstract

To investigate the immunological features of human T lymphotropic virus type II (HTLV-II) infection and specific mechanisms whereby HTLV-II might influence the progression of HIV-1 disease in coinfected individuals, we have analyzed the production of the C-C chemokines RANTES and macrophage inflammatory proteins 1α and 1β (MIP-1α and MIP-1β) by PBMCs from HTLV-II-infected and HTLV-II/HIV-1-coinfected individuals. We observed spontaneous production of significant levels of MIP-1α and -1β and, to a lesser extent, RANTES, from individuals infected with HTLV-II alone or with concomitant HIV-1 infection. Spontaneous C-C chemokine production was not observed in PBMCs from uninfected or HIV-1-infected individuals. Although HTLV-II is known to preferentially infect CD8+ lymphocytes in vivo, we observed that whereas RANTES was produced exclusively by the CD8+-enriched fraction, MIP-1α and -1β were produced by both the CD8+-enriched and CD8+-depleted fractions of HTLV-II-infected PBMCs. RT-PCR demonstrated active expression of the HTLV-II regulatory protein Tax in the infected CD8+ T lymphocyte population, and it was further shown that Tax transactivates the promoters of MIP-1β and RANTES. Therefore, it appears that HTLV-II stimulates the production of C-C chemokines both directly at a transcriptional level via the viral transactivator Tax and also indirectly. Although the HTLV-II-infected individuals in this study are all virtually asymptomatic, they certainly display an abnormal immune phenotype. Moreover, our findings suggest that HTLV-II, via chemokine production, would be expected to alter the progression of HIV-1 infection in coinfected individuals.

Phenotypic differences between healthy effector CTL and leukemic LGL cells support the notion of antigen-triggered clonal transformation in T-LGL leukemia

“…For example, various cytokines that were significantly altered in expression in LGL patients versus healthy controls are produced typically by CD8+ cells during viral infections, and some of them are almost invariably associated with viral processes. Examples of such cytokines include IFN-γ and chemokines CXCL10 (IP10) and CXCL8 (IL-8) [51][52][53][54][55]. Interestingly, up-regulation of phosphorylated AKT and ERK, previously found in LGL [36,56], can be caused by various chemokines such as CXCL8 (IL-8), which may prevent homeostatic apoptosis.…”

Dengue Virus Selectively Induces Human Mast Cell Chemokine Production

“…Human immunodeficiency virus infection of both activated and naive Th1 cells results in significant levels of RANTES, MIP-1␣, and MIP-1␤ by 4 to 6 days postinfection (3). In addition, PBMC obtained from individuals infected with human T-lymphotropic virus type II spontaneously secreted significant levels of MIP-1␣ and MIP-1␤ and to a lesser extent RANTES compared to uninfected controls (41). Both influenza A virus and Sendai virus infection of macrophages results in upregulation of, among others, RANTES, MIP-1␣, and MIP-1␤ (45).…”

Retroviral Interference on STAT Activation in Individuals Coinfected with Human T Cell Leukemia Virus Type 2 and HIV-1

“…In this regard, most seroprevalence studies have reported that HTLV-2 infection does not adversely affect the course of HIV-1 disease (8,19,20). Indeed, we and others have previously shown that HTLV-2 infection can potentially interfere with the replicative capacity of HIV-1 by up-regulating the secretion of HIV-1 suppressive chemokines, in particular C-C chemokine ligand 3/macrophage-inflammatory protein-1␣ (22,23).…”