tetano
Editor, Senior Moderator
J Cell Physiol. 2011 Feb 22. doi: 10.1002/jcp.22696. [Epub ahead of print]
Pepstatin a alters host cell autophagic machinery and leads to a decrease in influenza a virus production.
Matarrese P, Nencioni L, Checconi P, Ciarlo L, Gambardella L, Ascione B, Sgarbanti R, Garaci E, Malorni W, Palamara AT.
Department of Drug Research and Medicine Evaluation, Istituto Superiore di Sanita', Rome, Italy; Center of Integrated Metabolomics, Rome, Italy.
Abstract
Autophagy is a survival mechanism that can take place in cells under metabolic stress and through which cells can recycle waste material. Disturbances in autophagic processes appear to be associated with a number of human pathologies, including viral infections. It has been hypothesized that viruses can subvert autophagy in order to penetrate the host cell and replicate. Because it has been suggested that autophagy is be involved in influenza A virus replication, we analyzed the effects of two inhibitors of lysosomal proteases on the cellular control of influenza A virus replication. In particular, we used biochemical and morphological analyses to evaluate the modulation of influenza A/Puerto Rico/8/34 H1N1 virus production in the presence of CA074 and Pepstatin A, inhibitors of cathepsin proteases B and D, respectively. We found that Pepstatin A, but not CA074, significantly hindered influenza virus replication, probably by modulating host cell autophagic/apoptotic responses. These results are of potential interest to provide useful insights into the molecular pathways exploited by the influenza in order to replicate and to identify further cellular factors as targets for the development of innovative antiviral strategies. J. Cell. Physiol. ? 2011 Wiley Periodicals, Inc.
Copyright ? 2011 Wiley Periodicals, Inc.
PMID: 21344392 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21344392
Pepstatin a alters host cell autophagic machinery and leads to a decrease in influenza a virus production.
Matarrese P, Nencioni L, Checconi P, Ciarlo L, Gambardella L, Ascione B, Sgarbanti R, Garaci E, Malorni W, Palamara AT.
Department of Drug Research and Medicine Evaluation, Istituto Superiore di Sanita', Rome, Italy; Center of Integrated Metabolomics, Rome, Italy.
Abstract
Autophagy is a survival mechanism that can take place in cells under metabolic stress and through which cells can recycle waste material. Disturbances in autophagic processes appear to be associated with a number of human pathologies, including viral infections. It has been hypothesized that viruses can subvert autophagy in order to penetrate the host cell and replicate. Because it has been suggested that autophagy is be involved in influenza A virus replication, we analyzed the effects of two inhibitors of lysosomal proteases on the cellular control of influenza A virus replication. In particular, we used biochemical and morphological analyses to evaluate the modulation of influenza A/Puerto Rico/8/34 H1N1 virus production in the presence of CA074 and Pepstatin A, inhibitors of cathepsin proteases B and D, respectively. We found that Pepstatin A, but not CA074, significantly hindered influenza virus replication, probably by modulating host cell autophagic/apoptotic responses. These results are of potential interest to provide useful insights into the molecular pathways exploited by the influenza in order to replicate and to identify further cellular factors as targets for the development of innovative antiviral strategies. J. Cell. Physiol. ? 2011 Wiley Periodicals, Inc.
Copyright ? 2011 Wiley Periodicals, Inc.
PMID: 21344392 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21344392