Human herpesvirus 8-encoded interleukin 6 activates HIV-1 in the U1 monocytic cell line.
OBJECTIVE
Human herpesvirus 8 (HHV-8) encodes a viral interleukin 6 (vIL-6) which is structurally and functionally similar to human interleukin 6 (hIL-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 upregulate HIV-1, and to determine the interactions of this virokine (viral cytokine) with the components of the interleukin 6 (IL-6) receptor complex.


METHODS
Recombinant HHV-8 vIL-6 (rvIL-6) was assayed for bioactivity in the IL-6-dependent cell line MH60.BSF2. HIV-1 p24 production by the 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 p24 production after neutralization of components of the IL-6 receptor complex, 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 cells, and readily upregulated HIV-1 p24 production in U1 monocytic cells, but not in ACH-2 T cells. The vIL-6 appeared to utilize the IL-6-specific component 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 expression in monocytic cells, and therefore may play a role in AIDS pathogenesis in individuals infected with both viruses.
Gage
J R
JR
Department of Obstetrics and Gynecology, Osaka University, Japan.
Breen
E C
EC
Echeverri
A
A
Magpantay
L
L
Kishimoto
T
T
Miles
S
S
Martínez-Maza
O
O
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002460:Cell Line; D050822:Cytokine Receptor gp130; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000254:growth & development*; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000821:virology; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*; D014775:Virus Activation
D015703:Antigens, CD; D016655:HIV Core Protein p24; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D050822:Cytokine Receptor gp130