Increased monokines in cytomegalovirus infected myelomonocytic cell cultures

Turtinen, Lloyd W.; Assimacopoulos, A.; Haase, Ashley T.

doi:10.1016/0882-4010(89)90032-6

Cited by 21 publications

(17 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous analyses have shown that HCMVinfected THP-1 cultures produce TNF (87), a known activator of caspase-8 that could bind death receptors on infected cells. These early analyses also suggested that the TNF was largely produced by uninfected cells within the THP-1 cultures, consistent with other reports of HCMV-induced bystander effects (22,87). Other investigators have shown that HCMV downregulates TNF receptor 1 (TNFR1) on infected THP-1 cells (3), and this mechanism may be sufficient to evade the consequences of TNF produced by bystander cells.…”

Section: Discussionsupporting

confidence: 73%

“…Donor-to-donor variability inherent in primary monocyte-derived macrophages contrasts with more uniform responses of THP-1 cells, making this cell line useful in virus-host cell interaction studies (12). Previous evaluations of HCMV infections of THP-1 cells have explored the nonpermissive state of undifferentiated cells (5,30,31,42,56,60,87,91,92). In contrast, our current studies have focused on cells permissive to viral replication.…”

Section: Discussionmentioning

confidence: 64%

See 1 more Smart Citation

The Human Cytomegalovirus UL36 Gene Controls Caspase-Dependent and -Independent Cell Death Programs Activated by Infection of Monocytes Differentiating to Macrophages

McCormick

Roback

Livingston-Rosanoff

et al. 2010

J Virol

View full text Add to dashboard Cite

The cellular protease caspase-8 activates extrinsic apoptosis and also functions to promote monocyteto-macrophage differentiation. Differentiation-induced alterations to antiviral caspase-8-dependent cell death pathways are unclear. Here, we show THP-1 monocyte-to-macrophage differentiation alters the specific cell death pathways activated in response to human cytomegalovirus (HCMV) infection. Employing viruses with mutations in UL36, the gene that encodes the viral inhibitor of caspase-8 activation (vICA), our data indicate that both caspase-dependent and -independent death pathways are activated in response to infection. Activation of caspase-dependent and -independent cell death responses restricted growth of vICA-deficient viruses, and vICA/pUL36 inhibited either response. Thus, these studies also reveal that the UL36 gene controls a caspase-independent cell death pathway. The impact of caspases on control of antiviral responses differed at early and late stages of macrophage differentiation. Early in differentiation, vICA-deficient virus-induced cell death was dependent on caspases and inhibited by the pan-caspase inhibitor z-VAD(OMe)-fluoromethyl ketone. In contrast, virus-induced death at late times of differentiation was caspase independent. Additional unlabeled and fluorescent inhibitors indicated that caspase-8 promoted death from within infected cells at early but not late stages of differentiation. These data highlight the multifunctional role of vICA/pUL36 as HCMV encounters various antiviral responses during macrophage differentiation.Based on the frequency of infected cells in patients with disseminated disease, monocytes and monocyte-derived macrophages are important to the pathogenesis of human cytomegalovirus (HCMV) (8,24,32). Further, peripheral blood monocytes and granulocyte-macrophage progenitors are suggested to be latent reservoirs as healthy seropositive individuals carry HCMV DNA in these cells, a result consistent with the maintenance of latent genomes within experimentally infected progenitors (6,37,38,58,72,76,79,80). Infected monocytes do not produce new virus; however, replication follows monocyte-macrophage differentiation whether induced by growth or proinflammatory cytokines or allogeneic stimulation. Evidence suggests that monocyte infections promote differentiation to a permissive, proinflammatory macrophage (14, 74). Thus, the production of new progeny is highly dependent on cellular differentiation. Monocytes, cells undergoing macrophage differentiation, and mature macrophages differ in the expression patterns of specific genes, including those important to cell death control (44, 49). Whether any change in expression of cell death control genes influences cell death pathways activated by HCMV infection is unclear. The current study addresses this question by evaluating the requirement for one viral cell death suppressor during productive infection of monocytes at different stages of macrophage differentiation.HCMV and the related murine cytomegalovirus (MCMV) encode several...

show abstract

Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 64%

The Human Cytomegalovirus UL36 Gene Controls Caspase-Dependent and -Independent Cell Death Programs Activated by Infection of Monocytes Differentiating to Macrophages

McCormick

Roback

Livingston-Rosanoff

et al. 2010

J Virol

View full text Add to dashboard Cite

show abstract

“…4 B) were negative. This rate of (nonproductive) infection corresponds closely to rates ( 1% to 9%) previously reported (33,34), although it is considerably lower than the 40% recently reported by others (35). Among monocytes in the CMV-exposed cultures, 1 per 102 to 1 per 103 monocytes expressed TNF-a transcripts (Fig.…”

Section: Methodssupporting

confidence: 49%

Cytomegalovirus induction of tumor necrosis factor-alpha by human monocytes and mucosal macrophages.

et al. 1992

View full text Add to dashboard Cite

Cytomegalovirus (CMV) is a major cause of inflammatory organ disease in immunosuppressed persons. To elucidate the mechanisms of CMV-induced inflammation, we investigated whether tumor necrosis factor-a (TNF-a) was involved in the pathogenesis of CMV colitis in patients with AIDS. In in situ hybridization experiments, TNF-a mRNA was shown to be abundantly present in colonic mucosa from AIDS patients with CMV colitis but not in colonic mucosa from control (AIDS and normal) subjects. The TNF-a transcripts, identified in macrophage-like cells containing cytomegalic inclusions, were positively associated with CMV, but not HIV-1, within the mucosa.

show abstract

“…In addition, infection of THP-I cells with the laboratory strain ofCMV AD 169 resulted in an increase in TNF protein production (37). This study represents the first report of the effect of specific viral proteins on expression of the TNF gene.…”

mentioning

confidence: 78%

The immediate early genes of human cytomegalovirus upregulate tumor necrosis factor-alpha gene expression.

Geist¹,

Monick²,

Stinski³

et al. 1994

J. Clin. Invest.

View full text Add to dashboard Cite

Cytomegalovirus (CMV) is an important cause of disease in the immunocompromised patient and CMV infection is associated with predominantly mononuclear inflammatory response. Since products of the CMV immediate early (IE) gene region are potent trans-activators, we used the monocyte cell line THP-1 and a transient transfection assay to determine if these viral proteins upregulate expression of the TNF gene. The IE genes of CMV upregulated TNF gene activity as judged by increases in promoter activity, steady state mRNA, and protein production. The presence or absence of the 3' untranslated region of the TNF gene did not affect gene expression induced by the IE gene products. These studies suggest that activation of TNF gene expression by the CMV IE gene products may, in part, account for the inflammatory response associated with CMV infections. (J. Clin. Invest. 1994. 93:474-478.)

show abstract

Increased monokines in cytomegalovirus infected myelomonocytic cell cultures

Cited by 21 publications

References 20 publications

The Human Cytomegalovirus UL36 Gene Controls Caspase-Dependent and -Independent Cell Death Programs Activated by Infection of Monocytes Differentiating to Macrophages

The Human Cytomegalovirus UL36 Gene Controls Caspase-Dependent and -Independent Cell Death Programs Activated by Infection of Monocytes Differentiating to Macrophages

Cytomegalovirus induction of tumor necrosis factor-alpha by human monocytes and mucosal macrophages.

The immediate early genes of human cytomegalovirus upregulate tumor necrosis factor-alpha gene expression.

Contact Info

Product

Resources

About