Digoxin suppresses HIV-1 replication by altering viral RNA processing.
To develop new approaches to control HIV-1 replication, we examined the capacity of recently described small molecular modulators of RNA splicing for their effects on viral RNA metabolism. Of the drugs tested, digoxin was found to induce a dramatic inhibition of HIV-1 structural protein synthesis, a...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-03-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3610647?pdf=render |
| _version_ | 1819261335538499584 |
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| author | Raymond W Wong Ahalya Balachandran Mario A Ostrowski Alan Cochrane |
| author_facet | Raymond W Wong Ahalya Balachandran Mario A Ostrowski Alan Cochrane |
| author_sort | Raymond W Wong |
| collection | DOAJ |
| description | To develop new approaches to control HIV-1 replication, we examined the capacity of recently described small molecular modulators of RNA splicing for their effects on viral RNA metabolism. Of the drugs tested, digoxin was found to induce a dramatic inhibition of HIV-1 structural protein synthesis, a response due, in part, to reduced accumulation of the corresponding viral mRNAs. In addition, digoxin altered viral RNA splice site use, resulting in loss of the essential viral factor Rev. Digoxin induced changes in activity of the CLK family of SR protein kinases and modification of several SR proteins, including SRp20 and Tra2β, which could account for the effects observed. Consistent with this hypothesis, overexpression of SRp20 elicited changes in HIV-1 RNA processing similar to those observed with digoxin. Importantly, digoxin was also highly active against clinical strains of HIV-1 in vitro, validating this novel approach to treatment of this infection. |
| first_indexed | 2024-12-23T19:40:10Z |
| format | Article |
| id | doaj.art-95a9ba8c7b84431d9b7b397a830a71d8 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-23T19:40:10Z |
| publishDate | 2013-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-95a9ba8c7b84431d9b7b397a830a71d82022-12-21T17:33:41ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-03-0193e100324110.1371/journal.ppat.1003241Digoxin suppresses HIV-1 replication by altering viral RNA processing.Raymond W WongAhalya BalachandranMario A OstrowskiAlan CochraneTo develop new approaches to control HIV-1 replication, we examined the capacity of recently described small molecular modulators of RNA splicing for their effects on viral RNA metabolism. Of the drugs tested, digoxin was found to induce a dramatic inhibition of HIV-1 structural protein synthesis, a response due, in part, to reduced accumulation of the corresponding viral mRNAs. In addition, digoxin altered viral RNA splice site use, resulting in loss of the essential viral factor Rev. Digoxin induced changes in activity of the CLK family of SR protein kinases and modification of several SR proteins, including SRp20 and Tra2β, which could account for the effects observed. Consistent with this hypothesis, overexpression of SRp20 elicited changes in HIV-1 RNA processing similar to those observed with digoxin. Importantly, digoxin was also highly active against clinical strains of HIV-1 in vitro, validating this novel approach to treatment of this infection.http://europepmc.org/articles/PMC3610647?pdf=render |
| spellingShingle | Raymond W Wong Ahalya Balachandran Mario A Ostrowski Alan Cochrane Digoxin suppresses HIV-1 replication by altering viral RNA processing. PLoS Pathogens |
| title | Digoxin suppresses HIV-1 replication by altering viral RNA processing. |
| title_full | Digoxin suppresses HIV-1 replication by altering viral RNA processing. |
| title_fullStr | Digoxin suppresses HIV-1 replication by altering viral RNA processing. |
| title_full_unstemmed | Digoxin suppresses HIV-1 replication by altering viral RNA processing. |
| title_short | Digoxin suppresses HIV-1 replication by altering viral RNA processing. |
| title_sort | digoxin suppresses hiv 1 replication by altering viral rna processing |
| url | http://europepmc.org/articles/PMC3610647?pdf=render |
| work_keys_str_mv | AT raymondwwong digoxinsuppresseshiv1replicationbyalteringviralrnaprocessing AT ahalyabalachandran digoxinsuppresseshiv1replicationbyalteringviralrnaprocessing AT marioaostrowski digoxinsuppresseshiv1replicationbyalteringviralrnaprocessing AT alancochrane digoxinsuppresseshiv1replicationbyalteringviralrnaprocessing |