scholarly journals Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death

2017 ◽  
Author(s):  
Laurelle Jackson ◽  
Jessica Hunter ◽  
Sandile Cele ◽  
Isabella Markham Ferreira ◽  
Andrew Young ◽  
...  
Keyword(s):  
Cell Death ◽  
Lymph Node ◽  
Hiv Transmission ◽  
Neutralizing Antibody ◽  
Force Of Infection ◽  
Infected Lymph Node ◽  
A Cell ◽  
Lymph Node Cells ◽  
Infected Cells

AbstractHIV has been reported to be cytotoxic in vitro and in lymph node infection models. Using a computational approach, we found that partial inhibition of transmission which involves multiple virions per cell could lead to increased numbers of live infected cells if the number of viral DNA copies remains above one after inhibition, as eliminating the surplus viral copies reduces cell death. Using a cell line, we observed increased numbers of live infected cells when infection was partially inhibited with the antiretroviral efavirenz or neutralizing antibody. We then used efavirenz at concentrations reported in lymph nodes to inhibit lymph node infection by partially resistant HIV mutants. We observed more live infected lymph node cells, but with fewer HIV DNA copies per cell, relative to no drug. Hence, counterintuitively, limited attenuation of HIV transmission per cell may increase live infected cell numbers in environments where the force of infection is high.

scholarly journals Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Laurelle Jackson ◽  
Jessica Hunter ◽  
Sandile Cele ◽  
Isabella Markham Ferreira ◽  
Andrew C Young ◽  
...  
Keyword(s):  
Cell Death ◽  
Lymph Node ◽  
Hiv Transmission ◽  
Neutralizing Antibody ◽  
Force Of Infection ◽  
Infected Lymph Node ◽  
A Cell ◽  
Lymph Node Cells ◽  
Infected Cells

HIV has been reported to be cytotoxic in vitro and in lymph node infection models. Using a computational approach, we found that partial inhibition of transmissions of multiple virions per cell could lead to increased numbers of live infected cells. If the number of viral DNA copies remains above one after inhibition, then eliminating the surplus viral copies reduces cell death. Using a cell line, we observed increased numbers of live infected cells when infection was partially inhibited with the antiretroviral efavirenz or neutralizing antibody. We then used efavirenz at concentrations reported in lymph nodes to inhibit lymph node infection by partially resistant HIV mutants. We observed more live infected lymph node cells, but with fewer HIV DNA copies per cell, relative to no drug. Hence, counterintuitively, limited attenuation of HIV transmission per cell may increase live infected cell numbers in environments where the force of infection is high.

scholarly journals ANTIBODY FORMATION INITIATED IN VITRO

1963 ◽  
Vol 117 (4) ◽  
pp. 595-602 ◽  
Author(s):  
M. Fishman ◽  
F. L. Adler
Keyword(s):  
Lymph Node ◽  
Specific Antibody ◽  
Antibody Formation ◽  
Diffusion Chamber ◽  
A Cell ◽  
Lymph Node Cells ◽  
Chamber Technique

The diffusion chamber technique permitted the demonstration of specific antibody formation in x-irradiated recipients of such chambers filled with normal lymph node cells and a cell-free homogenate of macrophages which had been incubated in intro with T2 bacteriophage. The activity of the cell-free homogenate was retained in its RNA fraction isolated by means of the phenol method. No antibody formation occurred if such RNA was treated with RNAase. On sucrose gradients (5 to 20 per cent), the active RNA was found to be present in the top third layer. The question of the possible presence of antigen complexed to the RNA is discussed.

scholarly journals Author response: Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death

2017 ◽  
Author(s):  
Laurelle Jackson ◽  
Jessica Hunter ◽  
Sandile Cele ◽  
Isabella Markham Ferreira ◽  
Andrew C Young ◽  
...  
Keyword(s):  
Cell Death ◽  
Lymph Node ◽  
Hiv Infection ◽  
Author Response ◽  
Infected Lymph Node ◽  
Lymph Node Cells

Increased cell death in osteopontin-deficient cardiac fibroblasts occurs by a caspase-3-independent pathway

2004 ◽  
Vol 287 (4) ◽  
pp. H1730-H1739 ◽  
Author(s):  
Ron Zohar ◽  
Baoqian Zhu ◽  
Peter Liu ◽  
Jaro Sodek ◽  
C. A. McCulloch
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Cardiac Fibroblasts ◽  
Chromatin Condensation ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tunel Staining ◽  
Wild Type ◽  
Nuclear Fragmentation ◽  
A Cell

Reperfusion-induced oxidative injury to the myocardium promotes activation and proliferation of cardiac fibroblasts and repair by scar formation. Osteopontin (OPN) is a proinflammatory cytokine that is upregulated after reperfusion. To determine whether OPN enhances fibroblast survival after exposure to oxidants, cardiac fibroblasts from wild-type (WT) or OPN-null (OPN−/−) mice were treated in vitro with H2O2to model reperfusion injury. Within 1 h, membrane permeability to propidium iodide (PI) was increased from 5 to 60% in OPN−/−cells but was increased to only 20% in WT cells. In contrast, after 1–8 h of treatment with H2O2, the percent of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-stained cells was more than twofold higher in WT than OPN−/−cells. Electron microscopy of WT cells treated with H2O2showed chromatin condensation, nuclear fragmentation, and cytoplasmic and nuclear shrinkage, which are consistent with apoptosis. In contrast, H2O2-treated OPN−/−cardiac fibroblasts exhibited cell and nuclear swelling and membrane disruption that are indicative of cell necrosis. Treatment of OPN−/−and WT cells with a cell-permeable caspase-3 inhibitor reduced the percentage of TUNEL staining by more than fourfold in WT cells but decreased staining in OPN−/−cells by ∼30%. Although the percentage of PI-permeable WT cells was reduced threefold, the percent of PI-permeable OPN−/−cells was not altered. Restoration of OPN expression in OPN−/−fibroblasts reduced the percentage of PI-permeable cells but not TUNEL staining after H2O2treatment. Thus H2O2-induced cell death in OPN-deficient cardiac fibroblasts is mediated by a caspase-3-independent, necrotic pathway. We suggest that the increased expression of OPN in the myocardium after reperfusion may promote fibrosis by protecting cardiac fibroblasts from cell death.

scholarly journals Akt Interacts with Usutu Virus Polymerase, and Its Activity Modulates Viral Replication

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 244
Author(s):  
Laura Albentosa-González ◽  
Rosario Sabariegos ◽  
Armando Arias ◽  
Pilar Clemente-Casares ◽  
Antonio Mas
Keyword(s):  
Public Health ◽  
Confocal Microscopy ◽  
Viral Replication ◽  
Insufficient Data ◽  
Health Concerns ◽  
Usutu Virus ◽  
A Cell ◽  
Infected Cells ◽  
Specific Inhibitors

Usutu virus (USUV) is a flavivirus that mainly infects wild birds through the bite of Culex mosquitoes. Recent outbreaks have been associated with an increased number of cases in humans. Despite being a growing source of public health concerns, there is yet insufficient data on the virus or host cell targets for infection control. In this work we have investigated whether the cellular kinase Akt and USUV polymerase NS5 interact and co-localize in a cell. To this aim, we performed co-immunoprecipitation (Co-IP) assays, followed by confocal microscopy analyses. We further tested whether NS5 is a phosphorylation substrate of Akt in vitro. Finally, to examine its role in viral replication, we chemically silenced Akt with three inhibitors (MK-2206, honokiol and ipatasertib). We found that both proteins are localized (confocal) and pulled down (Co-IP) together when expressed in different cell lines, supporting the fact that they are interacting partners. This possibility was further sustained by data showing that NS5 is phosphorylated by Akt. Treatment of USUV-infected cells with Akt-specific inhibitors led to decreases in virus titers (>10-fold). Our results suggest an important role for Akt in virus replication and stimulate further investigations to examine the PI3K/Akt/mTOR pathway as an antiviral target.

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