Abrogation of in vitro suppression of human immunodeficiency virus type 1 (HIV-1) replication mediated by CD8+ T lymphocytes of asymptomatic HIV-1 carriers by staphylococcal enterotoxin B and phorbol esters through induction of tumor necrosis factor alpha.

1997 ◽  
Vol 71 (10) ◽  
pp. 7560-7566 ◽  
Author(s):  
M Kubo ◽  
T Ohashi ◽  
M Fujii ◽  
S Oka ◽  
A Iwamoto ◽  
...  
Keyword(s):  
Phorbol Esters ◽  
Staphylococcal Enterotoxin B ◽  
Necrosis Factor Alpha ◽  
Immunodeficiency Virus ◽  
Factor Alpha ◽  
Hiv 1 ◽  
Necrosis Factor ◽  
Asymptomatic Hiv

scholarly journals Studies of Ebola Virus Glycoprotein-Mediated Entry and Fusion by Using Pseudotyped Human Immunodeficiency Virus Type 1 Virions: Involvement of Cytoskeletal Proteins and Enhancement by Tumor Necrosis Factor Alpha

2005 ◽  
Vol 79 (2) ◽  
pp. 918-926 ◽  
Author(s):  
Akihito Yonezawa ◽  
Marielle Cavrois ◽  
Warner C. Greene
Keyword(s):  
Human Immunodeficiency Virus ◽  
Tumor Necrosis ◽  
Ebola Virus ◽  
Target Cells ◽  
Necrosis Factor Alpha ◽  
Immunodeficiency Virus ◽  
Factor Alpha ◽  
Hiv 1 ◽  
Necrosis Factor

ABSTRACT The Ebola filoviruses are aggressive pathogens that cause severe and often lethal hemorrhagic fever syndromes in humans and nonhuman primates. To date, no effective therapies have been identified. To analyze the entry and fusion properties of Ebola virus, we adapted a human immunodeficiency virus type 1 (HIV-1) virion-based fusion assay by substituting Ebola virus glycoprotein (GP) for the HIV-1 envelope. Fusion was detected by cleavage of the fluorogenic substrate CCF2 by β-lactamase-Vpr incorporated into virions and released as a result of virion fusion. Entry and fusion induced by the Ebola virus GP occurred with much slower kinetics than with vesicular stomatitis virus G protein (VSV-G) and were blocked by depletion of membrane cholesterol and by inhibition of vesicular acidification with bafilomycin A1. These properties confirmed earlier studies and validated the assay for exploring other properties of Ebola virus GP-mediated entry and fusion. Entry and fusion of Ebola virus GP pseudotypes, but not VSV-G or HIV-1 Env pseudotypes, were impaired in the presence of the microtubule-disrupting agent nocodazole but were enhanced in the presence of the microtubule-stabilizing agent paclitaxel (Taxol). Agents that impaired microfilament function, including cytochalasin B, cytochalasin D, latrunculin A, and jasplakinolide, also inhibited Ebola virus GP-mediated entry and fusion. Together, these findings suggest that both microtubules and microfilaments may play a role in the effective trafficking of vesicles containing Ebola virions from the cell surface to the appropriate acidified vesicular compartment where fusion occurs. In terms of Ebola virus GP-mediated entry and fusion to various target cells, primary macrophages proved highly sensitive, while monocytes from the same donors displayed greatly reduced levels of entry and fusion. We further observed that tumor necrosis factor alpha, which is released by Ebola virus-infected monocytes/macrophages, enhanced Ebola virus GP-mediated entry and fusion to human umbilical vein endothelial cells. Thus, Ebola virus infection of one target cell may induce biological changes that facilitate infection of secondary target cells that play a key role in filovirus pathogenesis. Finally, these studies indicate that pseudotyping in the HIV-1 virion-based fusion assay may be a valuable approach to the study of entry and fusion properties mediated through the envelopes of other viral pathogens.

scholarly journals Elevated Levels of Tumor Necrosis Factor Alpha (TNF-α) in Human Immunodeficiency Virus Type 1-Transgenic Mice: Prevention of Death by Antibody to TNF-α

2002 ◽  
Vol 76 (22) ◽  
pp. 11710-11714 ◽  
Author(s):  
Swapan K. De ◽  
Krishnakumar Devadas ◽  
Abner Louis Notkins
Keyword(s):  
Human Immunodeficiency Virus ◽  
Transgenic Mice ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Immunodeficiency Virus ◽  
Factor Alpha ◽  
Hiv 1 ◽  
Necrosis Factor

ABSTRACT Homozygous human immunodeficiency virus type 1 (HIV-1)-transgenic mice (Tg26) appear normal at birth but die within 3 to 4 weeks. The skin of these animals shows diffuse scaling and high-level expression of both HIV-1 mRNA and gp120. Previous experiments showed that treatment with human chorionic gonadatropin (hCG) prevented death and the expression of HIV-1 mRNA and gp120. The present experiments were initiated to study the role of tumor necrosis factor alpha (TNF-α) in HIV-1-induced pathology. Examination of the sera of Tg26 mice revealed a 50-fold increase in TNF-α levels compared to those in nontransgenic mice. Treatment with antibody to TNF-α prevented death, resulted in near normal growth, and produced a marked decrease in skin lesions and a profound reduction in the expression of HIV-1 mRNA and gp120. Both TNF-α antibody and hCG reduced TNF-α levels in sera by approximately 75%. We conclude that TNF-α contributes in a major way to HIV-1-induced pathology in transgenic mice and that both hCG and antibody to TNF-α prevent the development of pathology by suppressing the level of TNF-α.

scholarly journals Dendritic Cells Infected with vpr-Positive Human Immunodeficiency Virus Type 1 Induce CD8+ T-Cell Apoptosis via Upregulation of Tumor Necrosis Factor Alpha

2007 ◽  
Vol 81 (14) ◽  
pp. 7388-7399 ◽  
Author(s):  
Biswanath Majumder ◽  
Narasimhan J. Venkatachari ◽  
Elizabeth A. Schafer ◽  
Michelle L. Janket ◽  
Velpandi Ayyavoo
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Immunodeficiency Virus ◽  
Factor Alpha ◽  
Hiv 1 ◽  
Necrosis Factor

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) plays a crucial role in viral replication and pathogenesis by inducing cell cycle arrest, apoptosis, translocation of preintegration complex, potentiation of glucocorticoid action, impairment of dendritic cell (DC) maturation, and T-cell activation. Recent studies involving the direct effects of Vpr on DCs and T cells indicated that HIV-1 containing Vpr selectively impairs phenotypic maturation, cytokine network, and antigen presentation in DCs and dysregulates costimulatory molecules and cytokine production in T cells. Here, we have further investigated the indirect effect of HIV-1 Vpr+ virus-infected DCs on the bystander CD8+ T-cell population. Our results indicate that HIV-1 Vpr+ virus-infected DCs dysregulate CD8+ T-cell proliferation and induce apoptosis. Vpr-containing virus-infected DC-mediated CD8+ T-cell killing occurred in part through enhanced tumor necrosis factor alpha production by infected DCs and subsequent induction of death receptor signaling and activation of the caspase 8-dependent pathway in CD8+ T cells. Collectively, these results provide evidence that Vpr could be one of the important contributors to the host immune escape by HIV-1 through its ability to dysregulate both directly and indirectly the DC biology and T-cell functions.

scholarly journals Cytokines regulate HIV-1 replication and lymphocyte apoptosis in vitro

2013 ◽  
Vol 94 (6) ◽  
pp. 906-910 ◽  
Author(s):  
S V Boichuk ◽  
P D Dunaev ◽  
I G Mustafin
Keyword(s):  
Flow Cytometry ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Lymphocyte Apoptosis ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Hiv 1 ◽  
Necrosis Factor

Aim. To study the ability of cytokines - interleukin-2, interleukin-7 and tumor necrosis factor alpha to induce human immunodeficiency virus type 1 (HIV-1) replication and lymphocyte apoptosis in vitro. Methods. Peripheral blood mononuclears were separated by centrifugation on a ficoll paque solution specific density gradient. Lymphocytes were cultivated in RPMI 1640 medium with addition of L-glutamine, embryonal bovine serum, antibiotics and cytokines (interleukines-2, -4, -7, tumor necrosis factor alpha). To infect the lymphocytes, a laboratory strain of HIV-1 NL4-3 (NIH ResReag. Prog., USA) was used. HIV-1 replication was assessed by р24gag viral protein level in culture supernatants (ELISA) and its cytozolic level in lymphocytes (flow cytometry). Lymphocyte apoptosis was assessed by flow cytometry using the following parameters: (1) decrease of transmembrane mitochondrial potential; (2) increase in phosphatidyl serine molecules expression. Lymphocyte activation was assessed by CD25 and HLA-DR molecules expression (flow cytometry). Results. Cytokines induce the HIV-1 replication in lymphocytes in vitro. HIV-1 replication was noted only if inactivated lymphocytes were present in the culture. At the same time, lymphocytes not expressing the classical activation markers (CD25 and HLA-DR) were present among the lymphocytes producing HIV-1 indicating the possible alternative mechanism of HIV-1 replication, not dependent on cell activation. This fact might also be an evidence of viral replication processes in the pool of latently-infected lymphocytes, not expressing the classic activation markers. The abovementioned cytokines promote apoptotic death of uninfected lymphocytes in vitro, backing up the infected cells viability and thus promoting HIV-1 replication. Conclusion. Cytokines (interleukines-2, -4, -7, tumor necrosis factor alpha) which are known as factors supporting the immune system homeostasis and immune response formation, might also play a negative role in HIV-1 pathogenesis - induce HIV-1 replication in lymphocytes and, probably, lead to reactivation of the pool of latently-infected lymphocytes, deepening the lymphopenia and leading to disease progression.

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