A promonocytic cell model was used to investigate
cytokine gene transcription in U937 and U9-IIIB cells chronically infected with human immunodeficiency virus type 1 (HIV-1). The production of
interferon (alpha-1 interferon [IFN-alpha 1],
IFN-alpha 2, and IFN-beta),
interleukin (
interleukin 1 alpha [IL-1 alpha], IL-1 beta, and IL-6), and
tumor necrosis factor alpha (
TNF-alpha)
mRNA was characterized by quantitative polymerase chain reaction
mRNA phenotyping in U937 and U9-IIIB cells following
coinfection with Sendai paramyxovirus or stimulation with
lipopolysaccharide (LPS). Chronic HIV-1
infection of U9-IIIB cells resulted in a low constitutive level of transcription of TNF and
IL-1 genes but not IFN genes; however, when the cells were coinfected with Sendai virus, 10- to 20-fold higher levels of IFN-beta,
IL-1 beta,
IL-6, and
TNF-alpha mRNA were observed in U9-IIIB cells than in similarly induced U937 cells. The enhanced levels of
cytokine RNA in virus-infected U9-IIIB cells were also accompanied by higher levels of IFN
antiviral activity and TNF secretion than in U937 cells. Transcript levels for IFN-alpha 1 and
IFN-alpha 2 were equivalently induced in virus-infected U937 and U9-IIIB cells, indicating that a generalized derepression of
cytokine gene expression did not occur as a consequence of HIV-1
infection. When LPS was used as an inducer, a distinct pattern of
cytokine gene expression was detected in U9-IIIB cells.
TNF-alpha and
IL-1 beta but not IFN-alpha or IFN-beta transcripts were induced by LPS. These results suggest that HIV-1
infection of promonocytic cells may prime or sensitize cells such that subsequent antigenic challenge leads to coordinate enhancement of
cytokine gene expression.