Ligation of CR1 (C3b receptor, CD35) on CD4+ T lymphocytes enhances viral replication in HIV-infected cells

Apoptosis of bystander uninfected CD4+ T lymphocytes by neighboring HIV-infected cells is observed in cell culture and in lymphoid tissue of HIV-infected individuals. This study addresses whether antigen-presenting cells such as human macrophages mediate apoptosis of CD4+ T cells from HIV-infected individuals. Uninfected human macrophages, and to a larger degree, HIV-infected macrophages mediate apoptosis of T cells from HIV-infected, but not from uninfected control individuals. This macrophage-dependent killing targets CD4+, but not CD8+ T lymphocytes from HIV-infected individuals, and direct contact between macrophages and lymphocytes is required. Additional analyses indicated that the apoptosis-inducing ligands, FasL and tumor necrosis factor (TNF), mediate this macrophage-induced apoptosis of CD4+ T cells. These results support a role for macrophage-associated FasL and TNF in the selective depletion of CD4+ T cells in HIV-infected individuals.

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

Pathogens ◽

10.3390/pathogens10020244 ◽

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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Caspases in Virus-Infected Cells Contribute to Recognition by CD8+T Lymphocytes

The Journal of Immunology ◽

10.4049/jimmunol.1000050 ◽

2010 ◽

Vol 184 (9) ◽

pp. 5193-5199 ◽

Cited By ~ 12

Author(s):

Daniel López ◽

Margarita García-Calvo ◽

Geoffrey L. Smith ◽

Margarita Del Val

Keyword(s):

T Lymphocytes ◽

Cd8 T Lymphocytes ◽

Infected Cells

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Povidone-Iodine Attenuates Viral Replication in Ocular Cells: Implications for Ocular Transmission of RNA Viruses

Biomolecules ◽

10.3390/biom11050753 ◽

2021 ◽

Vol 11 (5) ◽

pp. 753

Author(s):

Sneha Singh ◽

Onkar B. Sawant ◽

Shahzad I. Mian ◽

Ashok Kumar

Keyword(s):

Epithelial Cells ◽

Viral Replication ◽

Povidone Iodine ◽

Rna Viruses ◽

Retinal Pigment ◽

Retinal Pigment Epithelial Cells ◽

Host Cells ◽

Eye Banking ◽

Antiviral Effects ◽

Infected Cells

Several RNA viruses, including SARS-CoV-2, can infect or use the eye as an entry portal to cause ocular or systemic diseases. Povidone-Iodine (PVP-I) is routinely used during ocular surgeries and eye banking as a cost-effective disinfectant due to its broad-spectrum antimicrobial activity, including against viruses. However, whether PVP-I can exert antiviral activities in virus-infected cells remains elusive. In this study, using Zika (ZIKV) and Chikungunya (CHIKV) virus infection of human corneal and retinal pigment epithelial cells, we report antiviral mechanisms of PVP-I. Our data showed that PVP-I, even at the lowest concentration (0.01%), drastically reduced viral replication in corneal and retinal cells without causing cellular toxicity. Antiviral effects of PVP-I against ZIKV and CHIKV were mediated by direct viral inactivation, thus attenuating the ability of the virus to infect host cells. Moreover, one-minute PVP-I exposure of infected ocular cells drastically reduced viral replication and the production of infectious progeny virions. Furthermore, viral-induced (CHIKV) expression of inflammatory genes (TNF-α, IL-6, IL-8, and IL1β) were markedly reduced in PVP-I treated corneal epithelial cells. Together, our results demonstrate potent antiviral effects of PVP-I against ZIKV and CHIKV infection of ocular cells. Thus, a low dose of PVP-I can be used during tissue harvesting for corneal transplants to prevent potential transmission of RNA viruses via infected cells.

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Notwithstanding Circumstantial Alibis, Cytotoxic T Cells Can Be Major Killers of HIV-1-Infected Cells

Journal of Virology ◽

10.1128/jvi.00306-16 ◽

2016 ◽

Vol 90 (16) ◽

pp. 7066-7083 ◽

Cited By ~ 14

Author(s):

Saikrishna Gadhamsetty ◽

Tim Coorens ◽

Rob J. de Boer

Keyword(s):

T Cells ◽

Viral Replication ◽

Cytotoxic T Cells ◽

Chronic Phase ◽

Replication Rate ◽

Immunodeficiency Virus ◽

Infected Cells ◽

Eclipse Phase ◽

Hiv 1

ABSTRACTSeveral experiments suggest that in the chronic phase of human immunodeficiency virus type 1 (HIV-1) infection, CD8+cytotoxic T lymphocytes (CTL) contribute very little to the death of productively infected cells. First, the expected life span of productively infected cells is fairly long, i.e., about 1 day. Second, this life span is hardly affected by the depletion of CD8+T cells. Third, the rate at which mutants escaping a CTL response take over the viral population tends to be slow. Our main result is that all these observations are perfectly compatible with killing rates that are much faster than one per day once we invoke the fact that infected cells proceed through an eclipse phase of about 1 day before they start producing virus. Assuming that the major protective effect of CTL is cytolytic, we demonstrate that mathematical models with an eclipse phase account for the data when the killing is fast and when it varies over the life cycle of infected cells. Considering the steady state corresponding to the chronic phase of the infection, we find that the rate of immune escape and the rate at which the viral load increases following CD8+T cell depletion should reflect the viral replication rate, ρ. A meta-analysis of previous data shows that viral replication rates during chronic infection vary between 0.5 ≤ ρ ≤ 1 day−1. Balancing such fast viral replication requires killing rates that are several times larger than ρ, implying that most productively infected cells would die by cytolytic effects.IMPORTANCEMost current data suggest that cytotoxic T cells (CTL) mediate their control of human immunodeficiency virus type 1 (HIV-1) infection by nonlytic mechanisms; i.e., the data suggest that CTL hardly kill. This interpretation of these data has been based upon the general mathematical model for HIV infection. Because this model ignores the eclipse phase between the infection of a target cell and the start of viral production by that cell, we reanalyze the same data sets with novel models that do account for the eclipse phase. We find that the data are perfectly consistent with lytic control by CTL and predict that most productively infected cells are killed by CTL. Because the killing rate should balance the viral replication rate, we estimate both parameters from a large set of published experiments in which CD8+T cells were depleted in simian immunodeficiency virus (SIV)-infected monkeys. This confirms that the killing rate can be much faster than is currently appreciated.

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Annexin A2 associates to feline calicivirus RNA in the replication complexes from infected cells and participates in an efficient viral replication

Virus Research ◽

10.1016/j.virusres.2018.12.003 ◽

2019 ◽

Vol 261 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Juan Carlos Santos-Valencia ◽

Clotilde Cancio-Lonches ◽

Adrian Trujillo-Uscanga ◽

Beatriz Alvarado-Hernández ◽

Anel Lagunes-Guillén ◽

...

Keyword(s):

Viral Replication ◽

Annexin A2 ◽

Feline Calicivirus ◽

Infected Cells ◽

Efficient Viral Replication

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Dengue Virus Activates the AMP Kinase-mTOR Axis To Stimulate a Proviral Lipophagy

Journal of Virology ◽

10.1128/jvi.02020-16 ◽

2017 ◽

Vol 91 (11) ◽

Cited By ~ 47

Author(s):

Tristan X. Jordan ◽

Glenn Randall

Keyword(s):

Dengue Virus ◽

Viral Replication ◽

Lipid Droplets ◽

Adenosine Monophosphate ◽

Denv Infection ◽

Ampk Signaling ◽

Selective Autophagy ◽

Dependent Inactivation ◽

Mtorc1 Signaling ◽

Infected Cells

ABSTRACT Robust dengue virus (DENV) replication requires lipophagy, a selective autophagy that targets lipid droplets. The autophagic mobilization of lipids leads to increased β-oxidation in DENV-infected cells. The mechanism by which DENV induces lipophagy is unknown. Here, we show that infection with DENV activates the metabolic regulator 5′ adenosine-monophosphate activated kinase (AMPK), and that the silencing or pharmacological inhibition of AMPK activity decreases DENV replication and the induction of lipophagy. The activity of the mechanistic target of rapamycin complex 1 (mTORC1) decreases in DENV-infected cells and is inversely correlated with lipophagy induction. Constitutive activation of mTORC1 by depletion of tuberous sclerosis complex 2 (TSC2) inhibits lipophagy induction in DENV-infected cells and decreases viral replication. While AMPK normally stimulates TSC2-dependent inactivation of mTORC1 signaling, mTORC1 inactivation is independent of AMPK activation during DENV infection. Thus, DENV stimulates and requires AMPK signaling as well as AMPK-independent suppression of mTORC1 activity for proviral lipophagy. IMPORTANCE Dengue virus alters host cell lipid metabolism to promote its infection. One mechanism for altered metabolism is the induction of a selective autophagy that targets lipid droplets, termed lipophagy. Lipophagy mobilizes lipid stores, resulting in enhanced β-oxidation and viral replication. We show here that DENV infection activates and requires the central metabolic regulator AMPK for its replication and the induction of lipophagy. This is required for the induction of lipophagy, but not basal autophagy, in DENV-infected cells.

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Murine Norovirus Replication Induces G0/G1Cell Cycle Arrest in Asynchronously Growing Cells

Journal of Virology ◽

10.1128/jvi.03673-14 ◽

2015 ◽

Vol 89 (11) ◽

pp. 6057-6066 ◽

Cited By ~ 16

Author(s):

Colin Davies ◽

Chris M. Brown ◽

Dana Westphal ◽

Joanna M. Ward ◽

Vernon K. Ward

Keyword(s):

Cell Cycle ◽

Viral Replication ◽

Host Cell ◽

Virus Replication ◽

Cell Cycle Progression ◽

Cycle Phase ◽

Murine Norovirus ◽

Cycle Progression ◽

Infected Cells ◽

Favorable Conditions

ABSTRACTMany viruses replicate most efficiently in specific phases of the cell cycle, establishing or exploiting favorable conditions for viral replication, although little is known about the relationship between caliciviruses and the cell cycle. Microarray and Western blot analysis of murine norovirus 1 (MNV-1)-infected cells showed changes in cyclin transcript and protein levels indicative of a G1phase arrest. Cell cycle analysis confirmed that MNV-1 infection caused a prolonging of the G1phase and an accumulation of cells in the G0/G1phase. The accumulation in G0/G1phase was caused by a reduction in cell cycle progression through the G1/S restriction point, with MNV-1-infected cells released from a G1arrest showing reduced cell cycle progression compared to mock-infected cells. MNV-1 replication was compared in populations of cells synchronized into specific cell cycle phases and in asynchronously growing cells. Cells actively progressing through the G1phase had a 2-fold or higher increase in virus progeny and capsid protein expression over cells in other phases of the cell cycle or in unsynchronized populations. These findings suggest that MNV-1 infection leads to prolonging of the G1phase and a reduction in S phase entry in host cells, establishing favorable conditions for viral protein production and viral replication. There is limited information on the interactions between noroviruses and the cell cycle, and this observation of increased replication in the G1phase may be representative of other members of theCaliciviridae.IMPORTANCENoroviruses have proven recalcitrant to growth in cell culture, limiting our understanding of the interaction between these viruses and the infected cell. In this study, we used the cell-culturable MNV-1 to show that infection of murine macrophages affects the G1/S cell cycle phase transition, leading to an arrest in cell cycle progression and an accumulation of cells in the G0/G1phase. Furthermore, we show that MNV replication is enhanced in the G1phase compared to other stages of the cell cycle. Manipulating the cell cycle or adapting to cell cycle responses of the host cell is a mechanism to enhance virus replication. To the best of our knowledge, this is the first report of a norovirus interacting with the host cell cycle and exploiting the favorable conditions of the G0/G1phase for RNA virus replication.

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