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Title: Oxygen tension level and human viral infections

Abstract

The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viralmore » infections.« less

Authors:
 [1];  [2];  [3]; ;  [3];  [2];  [2];  [4];  [2]
  1. Centre des Innovations Thérapeutiques en Oncologie et Hématologie (CITOH), CHU Saint-Louis, Paris (France)
  2. (France)
  3. Institut Cochin INSERM U1016, Paris (France)
  4. Laboratoire de Bactériologie-Virologie-Hygiène, CHU de Saint-Etienne, Saint-Etienne (France)
Publication Date:
OSTI Identifier:
22436641
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 444; Journal Issue: 1-2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIDS VIRUS; ANOXIA; CHEMOTHERAPY; GENES; HEPATITIS; IN VITRO; IN VIVO; METABOLISM; OXYGEN; RADIOTHERAPY; SARCOMAS; TRANSCRIPTION FACTORS

Citation Formats

Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr, Université Denis Diderot, Sorbonne Paris Cité Paris, Paris, Casetti, Luana, François, Jean-Hugues, Capron, Claude, Laboratoire d'Hématologie, Hôpital Ambroise Paré, Boulogne, Université de Versailles Saint-Quentin en Yvelynes, Versailles, Pillet, Sylvie, and Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon. Oxygen tension level and human viral infections. United States: N. p., 2013. Web. doi:10.1016/J.VIROL.2013.06.018.
Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr, Université Denis Diderot, Sorbonne Paris Cité Paris, Paris, Casetti, Luana, François, Jean-Hugues, Capron, Claude, Laboratoire d'Hématologie, Hôpital Ambroise Paré, Boulogne, Université de Versailles Saint-Quentin en Yvelynes, Versailles, Pillet, Sylvie, & Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon. Oxygen tension level and human viral infections. United States. doi:10.1016/J.VIROL.2013.06.018.
Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr, Université Denis Diderot, Sorbonne Paris Cité Paris, Paris, Casetti, Luana, François, Jean-Hugues, Capron, Claude, Laboratoire d'Hématologie, Hôpital Ambroise Paré, Boulogne, Université de Versailles Saint-Quentin en Yvelynes, Versailles, Pillet, Sylvie, and Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon. 2013. "Oxygen tension level and human viral infections". United States. doi:10.1016/J.VIROL.2013.06.018.
@article{osti_22436641,
title = {Oxygen tension level and human viral infections},
author = {Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr and Université Denis Diderot, Sorbonne Paris Cité Paris, Paris and Casetti, Luana and François, Jean-Hugues and Capron, Claude and Laboratoire d'Hématologie, Hôpital Ambroise Paré, Boulogne and Université de Versailles Saint-Quentin en Yvelynes, Versailles and Pillet, Sylvie and Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon},
abstractNote = {The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viral infections.},
doi = {10.1016/J.VIROL.2013.06.018},
journal = {Virology},
number = 1-2,
volume = 444,
place = {United States},
year = 2013,
month = 9
}
  • Measurements of tissue oxygen tension were made in human tumors which were being treated by high pressure oxygen radiotherapy. The measurements were made polarographically using a pulsed-voltage, membranecovered electrode system. The electrodes measure mean oxygen tension over a circular area of 200 mu in diameter every 17 seconds. While the patients were breathing air the mean oxygen tensions recorded in their tumors showed a very large scatter. In one patient's tumor which was studied the tension varied from 0 to 100 mm Hg. Breathing 100 per cent oxygen at one atmosphere usually but not always produced an increase in oxygenmore » tension. Breathing 100 per cent oxygen at four atmospheres produced an increase in oxygen tension in all of the tumor sites which were studied. Following irradiation there was an increase in tumor oxygen tension both while breathing air and 100 per cent oxygen at one atmosphere. The increase was, however, barely significant at the 5 per cent level. The rate of saturation of the tumors with oxygen was often slower than in normal skin. There was no systematic change following radiotherapy. Measurements of oxygen tension at one site in a tumor give no information concerning the oxygen tension at other sites. This emphasizes the lack of homogeneity of the vascular pattern in tumors. (auth)« less
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  • An expression vector was constructed that carries part of the human BK papovavirus with 0.5 kilobases of (2'-5')oligoadenylate (2-5A) synthetase cDNA inserted in inverted orientation downstream from the virion proteins (VP) promoter and the neomycin-resistance gene neo under the control of a simian virus 40 promoter. Cells transfected with this vector and selected for resistance to the neomycin derivative G418 synthesized RNA complementary to 2-5A synthetase mRNA. These cells lacked 2-5A synthetase activity, and the enzyme was not inducible by interferon. In contrast, 2-5A synthetase was induced in cells transfected with a control vector without the cDNA insert. Such cellsmore » were protected by interferon from RNA viruses, whereas cells lacking 2-5A synthetase were not protected from encephalomyocarditis virus, vesicular stomatitis virus, and Sindbis virus but were fully protected from influenza virus. These findings show that a high level of 2-5A synthetase is required for interferon-induced protection from the cytoplasmic RNA viruses tested.« less
  • Treatment for most persistent viral infections consists of palliative drug options rather than curative approaches. This is often because long-lasting viral DNA in infected cells is not affected by current antivirals, providing a source for viral persistence and reactivation. Targeting latent viral DNA itself could therefore provide a basis for novel curative strategies. DNA cleavage enzymes can be used to induce targeted mutagenesis of specific genes, including those of exogenous viruses. Although initial in vitro and even in vivo studies have been carried out using DNA cleavage enzymes targeting various viruses, many questions still remain concerning the feasibility of thesemore » strategies as they transition into preclinical research. Here, we review the most recent findings on DNA cleavage enzymes for human viral infections, consider the most relevant animal models for several human viral infections, and address issues regarding safety and enzyme delivery. Results from well-designed in vivo studies will ideally provide answers to the most urgent remaining questions, and allow continued progress toward clinical application. - Highlights: • Recent in vitro and in vivo results for DNA cleavage enzymes targeting persistent viral infections. • Analysis of the best animal models for testing enzymes for HBV, HSV, HIV and HPV. • Challenges facing in vivo delivery of therapeutic enzymes for persistent viral infections. • Safety issues to be addressed with proper animal studies.« less