Respiratory Syncytial Virus Infection Sensitizes Cells to Apoptosis Mediated by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand

Kotelkin, Alexander; Prikhod’ko, Elena A.; Cohen, Jeffrey I.; Collins, Peter L.; Bukreyev, and Alexander

doi:10.1128/jvi.77.17.9156-9172.2003

Cited by 120 publications

(125 citation statements)

References 77 publications

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“…This elevated DNA fragmentation is greater than the effect of TRAIL on untransfected MDM, where DNA fragmentation increased up to 1-fold. These observations suggest that adenovirus, like other reported viruses (31)(32)(33), may sensitize cells to TRAIL-induced apoptosis. More importantly, when MDM expressing Ad-DN-Akt were treated with rhTRAIL (50 ng/ml), there was a 13-fold increase in apoptosis as seen using DNA fragmentation ELISA ( p Ͻ 0.001, Fig.…”

Section: Akt-1 Is Required For Macrophage Survival Following Trail Trsupporting

confidence: 58%

TRAIL-Mediated Apoptosis in HIV-1-Infected Macrophages Is Dependent on the Inhibition of Akt-1 Phosphorylation

Huang

Erdmann

Peng

et al. 2006

The Journal of Immunology

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HIV-1 uses mononuclear phagocytes (monocytes, tissue macrophages, and dendritic cells) as a vehicle for its own dissemination and as a reservoir for continuous viral replication. The mechanism by which the host immune system clears HIV-1-infected macrophages is not understood. TRAIL may play a role in this process. TRAIL is expressed on the cell membrane of peripheral immune cells and can be cleaved into a soluble, secreted form. The plasma level of TRAIL is increased in HIV-1-infected patients, particularly those with high viral loads. To study the effect of elevated TRAIL on mononuclear phagocytes, we used recombinant human (rh) TRAIL and human monocyte-derived macrophages (MDM) as an in vitro model. Our results demonstrated rhTRAIL-induced apoptosis in HIV-1-infected MDM and inhibited viral replication, while having a reduced effect on uninfected MDM. HIV-1 infection significantly decreased Akt-1 phosphorylation; rhTRAIL exposure further decreased Akt-1 phosphorylation. Infection with a dominant-negative Akt-1 adenovirus potentiated rhTRAIL-induced apoptosis, while constitutively active Akt-1 blocked rhTRAIL-induced apoptosis in HIV-1-infected MDM. From this data we conclude the death ligand TRAIL preferentially provokes apoptosis of HIV-1-infected MDM, and the mechanism is reliant upon the inhibition of Akt-1 phosphorylation. Understanding this mechanism may facilitate the elimination of HIV-1-infected macrophages and lead to new therapeutic avenues for treatment of HIV-1 infection.

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Section: Akt-1 Is Required For Macrophage Survival Following Trail Trsupporting

confidence: 58%

TRAIL-Mediated Apoptosis in HIV-1-Infected Macrophages Is Dependent on the Inhibition of Akt-1 Phosphorylation

Huang

Erdmann

Peng

et al. 2006

The Journal of Immunology

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“…Virus-induced sensitization of infected target cells in response to TRAIL-induced apoptosis has been reported in various viruses, including respiratory syncytial virus, hepatitis B virus, hepatitis C virus, HIV, SIV, and Hendra virus (61)(62)(63)(64)(65)(66)(67)(68). Notably, in agreement with the present study (Fig.…”

Section: Discussionsupporting

confidence: 93%

“…Notably, in agreement with the present study (Fig. 3), the cell death sensitization by all aforementioned viruses is associated with the upregulation of Bax and/or downregulation of Bcl-2 and Bcl-x L (61-65), as well as the induction of cellular DR4 and DR5 (65)(66)(67)(68). Because a wide spectrum of viruses sensitizes cell death in such a similar and convergent way, such evidence suggests that the regulation of DR4 and DR5 plays common but critical roles in the virus-infected cells.…”

Section: Discussionsupporting

confidence: 93%

Endothelial Cell Sensitization by Death Receptor Fractions of an Anti–Dengue Nonstructural Protein 1 Antibody Induced Plasma Leakage, Coagulopathy, and Mortality in Mice

Sun

Chang

Lien

et al. 2015

The Journal of Immunology

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The mechanisms leading to the life-threatening dengue hemorrhagic fever (DHF) remain elusive. DHF preferentially occurs during secondary dengue infections, suggesting that aberrant immune responses are involved in its development. We previously demonstrated that the autoantibodies elicited by dengue virus (DENV) nonstructural protein 1 (NS1; anti–NS1 Igs) induce plasma leakage and mortality in mice with warfarinized anticoagulant suppression. However, the involved pathogenic Ig fractions of anti–NS1 Igs remain unclear. In this study, the autoreactive Igs in patients with DHF and in NS1-immunized rabbits crossreacted with TNF-related apoptosis-inducing ligand receptor 1 (death receptor [DR]4). Challenges with the DENV in a subcytotoxic dose sensitized endothelial cells to apoptosis. Treatments with the autoantibodies induced proapoptotic activities and suppressed the surface expression of endothelial anticoagulant thrombomodulin. Combined treatments comprising the DENV and DR4 affinity-purified fractions of anti–NS1 IgGs (anti–NS1-DR4 Ig), but not preimmune control IgGs, in subcytotoxic doses led to apoptosis in endothelial cells. Treatments with the anti–NS1-DR4 Ig led to plasma leakage, coagulopathy, and morality in mice with warfarinized anticoagulant suppression. These results suggest that DR4-induced endothelial cell sensitization through NS1-elicited autoantibodies exacerbates anticoagulant suppression, vascular injury, and plasma leakage. Detecting and blocking anti–DR Igs in patients may be novel strategies for managing severe DENV infection.

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“…In cultured respiratory epithelia, RSV infection directly results in expression of many pro-and anti-apoptotic factors. The intracellular balance of these factors may be pushed towards apoptosis through external mononuclear-induced cytotoxicity by binding of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to death receptor-4/5 (DR4/5) [47]. TRAIL is quickly expressed on monocytes following interferon-a or -c activation (common with RSV infection), and subsequent binding of DR4/5-expressing cells causes induction of apoptosis [48].…”

Section: Discussionmentioning

confidence: 99%

Reduced clearance of respiratory syncytial virus infection in a preterm lamb model

Meyerholz

Grubor

Fach

et al. 2004

Microbes and Infection

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Respiratory syncytial virus (RSV) causes significant respiratory disease in children worldwide. For the study of severe RSV disease seen in preterm infants, a suitable animal model is lacking. The novel hypothesis of this study was that preterm lambs are susceptible to bovine RSV (bRSV) infection, an analogous pneumovirus with ruminant host specificity, and that there would be age-dependent differences in select RSV disease parameters. During RSV infection, preterm lambs had elevated temperatures and respiration rates with mild anorexia and cough compared to controls. Gross lesions included multifocal consolidation and atelectasis with foci of hyperinflation. Microscopic lesions included multifocal alveolar septal thickening and bronchiolitis. Immunohistochemistry localized the RSV antigen to all layers of bronchiolar epithelium from a few basal cells to numerous sloughing epithelia. A few mononuclear cells were also immunoreactive. To assess for age-dependent differences in RSV infection, neonatal lambs were infected similarly to the preterm lambs or with a high-titer viral inoculum. Using morphometry at day 7 of infection, preterm lambs had significantly more cellular immunoreactivity for RSV antigen (P <0.05) and syncytial cell formation (P <0.05) than either group of neonatal lambs. This work suggests that perinatal RSV clearance is age-dependent, which may explain the severity of RSV infection in preterm infants. The preterm lamb model is useful for assessing agedependent mechanisms of severe RSV infection. RightsWorks produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted. AbstractRespiratory syncytial virus (RSV) causes significant respiratory disease in children worldwide. For the study of severe RSV disease seen in preterm infants, a suitable animal model is lacking. The novel hypothesis of this study was that preterm lambs are susceptible to bovine RSV (bRSV) infection, an analogous pneumovirus with ruminant host specificity, and that there would be age-dependent differences in select RSV disease parameters. During RSV infection, preterm lambs had elevated temperatures and respiration rates with mild anorexia and cough compared to controls. Gross lesions included multifocal consolidation and atelectasis with foci of hyperinflation. Microscopic lesions included multifocal alveolar septal thickening and bronchiolitis. Immunohistochemistry localized the RSV antigen to all layers of bronchiolar epithelium from a few basal cells to numerous sloughing epithelia. A few mononuclear cells were also immunoreactive. To assess for age-dependent differences in RSV infection, neonatal lambs were infected similarly to the preterm lambs or with a high-titer viral inoculum. Using morphometry at day 7 of infection, preterm lambs had significantly more cellular immunoreactivity for RSV antigen (P <0.05) and syncytial cell formation (P <0.05) than either group of neonatal lambs. This work suggests that peri...

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Respiratory Syncytial Virus Infection Sensitizes Cells to Apoptosis Mediated by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand

Abstract: Respiratory syncytial virus (RSV) is

Cited by 120 publications

References 77 publications

TRAIL-Mediated Apoptosis in HIV-1-Infected Macrophages Is Dependent on the Inhibition of Akt-1 Phosphorylation

TRAIL-Mediated Apoptosis in HIV-1-Infected Macrophages Is Dependent on the Inhibition of Akt-1 Phosphorylation

Endothelial Cell Sensitization by Death Receptor Fractions of an Anti–Dengue Nonstructural Protein 1 Antibody Induced Plasma Leakage, Coagulopathy, and Mortality in Mice

Reduced clearance of respiratory syncytial virus infection in a preterm lamb model

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