HTLV-II down-regulates HIV-1 replication in IL-2-stimulated primary PBMC of coinfected individuals through expression of MIP-1alpha.
The influence of human T-cell leukemia/lymphoma virus type II (HTLV-II) in individuals also infected with HIV-1 is poorly understood. To evaluate the reciprocal influence of HTLV-II and HIV-1 infection, primary peripheral blood mononuclear cell (PBMC) cultures from coinfected individuals were established in the presence of interleukin 2 (IL-2). In these cultures, the kinetics of HTLV-II replication always preceded those of HIV-1. Noteworthy, the kinetics of HIV-1 production were inversely correlated to the HTLV-II proviral load in vivo and its replication ex vivo. These observations suggested a potential interaction between the 2 retroviruses. In this regard, the levels of IL-2, IL-6, and tumor necrosis factor-alpha (TNF-alpha) were measured in the same coinfected PBMC cultures. Endogenous IL-2 was not produced, whereas IL-6 and TNF-alpha were secreted at levels compatible with their known ability to up-regulate HIV-1 expression. The HIV-suppressive CC-chemokines RANTES, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta were also determined in IL-2-stimulated PBMC cultures. Of interest, their kinetics and concentrations were inversely related to those of HIV-1 replication. Experiments were performed in which CD8(+) T cells or PBMCs from HTLV-II monoinfected individuals were cocultivated with CD4(+) T cells from HIV-1 monoinfected individuals separated by a semipermeable membrane in the presence or absence of antichemokine neutralizing antibodies. The results indicate that HTLV-II can interfere with the replicative potential of HIV-1 by up-regulating viral suppressive CC-chemokines and, in particular, MIP-1alpha. This study is the first report indicating that HTLV-II can influence HIV replication, at least in vitro, via up-regulation of HIV-suppressive chemokines. (Blood. 2000;95:2760-2769)
Casoli
C
C
Istituto di Patologia Medica, Università di Parma, Parma, Italy. claucaso@ipruniv.cce.unipr.it
Vicenzi
E
E
Cimarelli
A
A
Magnani
G
G
Ciancianaini
P
P
Cattaneo
E
E
Dall'Aglio
P
P
Poli
G
G
Bertazzoni
U
U
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology / Q000821:virology; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D015491:HTLV-II Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000097:blood* / Q000494:pharmacology; D008297:Male; D011533:Proviruses / Q000302:isolation & purification; D012044:Regression Analysis; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D007376:Interleukin-2; D019402:Macrophage Inflammatory Proteins