Objective: Human herpesvirus 8 (HHV-8) encodes a viral interleukin 6 (vIL-6
) which is structurally and functionally similar to human interleukin 6 (hI
L-6). Since hIL-6 has been shown to upregulate the expression of HIV-1, the
objectives of this study were to examine the ability of vIL-6 to upregulat
e HIV-1, and to determine the interactions of this virokine (viral cytokine
) with the components of the interleukin 6 (IL-6) receptor complex.
Design and methods: Recombinant HHV-8 vIL-6 (rvIL-6) was assayed for bioact
ivity in the IL-6-dependent cell line MH60.BSF2. HIV-1 p24 production by th
e U1 monocytic and ACH-2 T-cell lines, which are chronically infected with
HIV-1, was used to assess the ability of vIL-6 to affect HIV-1 expression.
hIL-6 and vIL-6 receptor utilization was determined by quantifying HIV-1 p2
4 production after neutralization of components of the IL-6 receptor comple
x, CD126'IL-6R' and CD130'gp130', on U1 cells with blocking antibodies.
Results: HHV-8 rvIL-6 was seen to have IL-6-like bioactivity in MH60.BSF2 c
ells, and readily upregulated HIV-1 p24 production in U1 monocytic cells, b
ut not in ACH-2 T cells. The vIL-6 appeared to utilize the IL-6-specific co
mponent of the IL-6 signaling complex, CD126'IL-6R', in U1 cells.
Conclusions: HHV-8 vIL-6 clearly has the potential to upregulate HIV-1 expr
ession in monocytic cells, and therefore may play a role in AIDS pathogenes
is in individuals infected with both viruses. (C) 1999 Lippincott Williams
& Wilkins.