Viral antigen stimulation of the production of human monokines capable of regulating HIV1 expression.
We have previously described model systems for cytokine-induced regulation of chronically HIV-infected promonocyte and T cell clones. Using these systems, we have shown that monokines contained in supernatants from LPS-stimulated human monocyte/macrophages (MO) up-regulate HIV expression, reflected by an increase in reverse transcriptase activity, viral RNA levels, and expressed viral proteins. Current studies were designed to determine whether viral Ag can interact with MO and secondarily affect HIV1 expression by stimulating monokine production. We found that certain herpes-group viruses, including CMV and EBV, augment HIV1 expression by inducing monokine production, whereas others, such as HSV1, HSV2, varicella-zoster virus, and human herpes virus 6 were unable to function in this capacity. The HSV1 and HSV2 Ag which failed to stimulate monokine production did not interfere with MO stimulation by CMV Ag, suggesting that failure to induce HIV expression was not attributable to MO suppression. When nonherpes group viruses were tested, we found that human adenovirus, hepatitis B virus, and vaccinia virus all failed to stimulate the production of monokines capable of activating HIV in the chronically infected cell lines. In contrast, HIV1 can augment its own expression by inducing the secretion of monokines which up-regulate HIV expression in the infected cells. The viral Ag-induced MO supernatants capable of up-regulating HIV expression did so in a dose-dependent manner, whereas viral Ag alone produced no significant change. Monokine production mediated by viral Ag was not attributable to contaminating endotoxin. These studies provide a model to determine whether other opportunistic infections may induce the expression of HIV by indirect mechanisms, such as the stimulation of cytokine production.
Clouse
K A
KA
Department of Microbiology, Georgetown University, Washington, D.C. 20007.
Robbins
P B
PB
Fernie
B
B
Ostrove
J M
JM
Fauci
A S
AS
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000260:Adenoviruses, Human / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D001685:Biological Factors / Q000096:biosynthesis* / Q000502:physiology; D002460:Cell Line; D004731:Endotoxins / Q000502:physiology; D015488:HIV Antigens / Q000276:immunology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D015846:Monokines; D018139:Simplexvirus / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D014775:Virus Activation
D000956:Antigens, Viral; D001685:Biological Factors; D004731:Endotoxins; D015488:HIV Antigens; D015846:Monokines