Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses
<p>Abstract</p> <p>Chloroquine is a 4-aminoquinoline previously used in malaria therapy and now becoming an emerging investigational antiviral drug due to its broad spectrum of antiviral activities. To explore whether the low pH-dependency of influenza A viruses might affect the an...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2007-05-01
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| Series: | Virology Journal |
| Online Access: | http://www.virologyj.com/content/4/1/39 |
| _version_ | 1818531204534632448 |
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| author | Vignolo Edoardo D'Ostilio Daniela Puzelli Simona Norelli Sandro Campitelli Laura Savarino Andrea Di Trani Livia Donatelli Isabella Cassone Antonio |
| author_facet | Vignolo Edoardo D'Ostilio Daniela Puzelli Simona Norelli Sandro Campitelli Laura Savarino Andrea Di Trani Livia Donatelli Isabella Cassone Antonio |
| author_sort | Vignolo Edoardo |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Chloroquine is a 4-aminoquinoline previously used in malaria therapy and now becoming an emerging investigational antiviral drug due to its broad spectrum of antiviral activities. To explore whether the low pH-dependency of influenza A viruses might affect the antiviral effects of chloroquine at clinically achievable concentrations, we tested the antiviral effects of this drug on selected human and avian viruses belonging to different subtypes and displaying different pH requirements. Results showed a correlation between the responses to chloroquine and NH<sub>4</sub>Cl, a lysosomotropic agent known to increase the pH of intracellular vesicles. Time-of-addition experiments showed that the inhibitory effect of chloroquine was maximal when the drug had been added at the time of infection and was lost after 2 h post-infection. This timing approximately corresponds to that of virus/cell fusion. Moreover, there was a clear correlation between the EC<sub>50 </sub>of chloroquine in vitro and the electrostatic potential of the HA subunit (HA2) mediating the virus/cell fusion process. Overall, the present study highlights the critical importance of a host cell factor such as intravesicular pH in determining the anti-influenza activity of chloroquine and other lysosomotropic agents.</p> |
| first_indexed | 2024-12-11T17:29:24Z |
| format | Article |
| id | doaj.art-e46e2c24ff094b5b8390277d37493c7f |
| institution | Directory Open Access Journal |
| issn | 1743-422X |
| language | English |
| last_indexed | 2024-12-11T17:29:24Z |
| publishDate | 2007-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj.art-e46e2c24ff094b5b8390277d37493c7f2022-12-22T00:56:52ZengBMCVirology Journal1743-422X2007-05-01413910.1186/1743-422X-4-39Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A virusesVignolo EdoardoD'Ostilio DanielaPuzelli SimonaNorelli SandroCampitelli LauraSavarino AndreaDi Trani LiviaDonatelli IsabellaCassone Antonio<p>Abstract</p> <p>Chloroquine is a 4-aminoquinoline previously used in malaria therapy and now becoming an emerging investigational antiviral drug due to its broad spectrum of antiviral activities. To explore whether the low pH-dependency of influenza A viruses might affect the antiviral effects of chloroquine at clinically achievable concentrations, we tested the antiviral effects of this drug on selected human and avian viruses belonging to different subtypes and displaying different pH requirements. Results showed a correlation between the responses to chloroquine and NH<sub>4</sub>Cl, a lysosomotropic agent known to increase the pH of intracellular vesicles. Time-of-addition experiments showed that the inhibitory effect of chloroquine was maximal when the drug had been added at the time of infection and was lost after 2 h post-infection. This timing approximately corresponds to that of virus/cell fusion. Moreover, there was a clear correlation between the EC<sub>50 </sub>of chloroquine in vitro and the electrostatic potential of the HA subunit (HA2) mediating the virus/cell fusion process. Overall, the present study highlights the critical importance of a host cell factor such as intravesicular pH in determining the anti-influenza activity of chloroquine and other lysosomotropic agents.</p>http://www.virologyj.com/content/4/1/39 |
| spellingShingle | Vignolo Edoardo D'Ostilio Daniela Puzelli Simona Norelli Sandro Campitelli Laura Savarino Andrea Di Trani Livia Donatelli Isabella Cassone Antonio Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses Virology Journal |
| title | Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses |
| title_full | Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses |
| title_fullStr | Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses |
| title_full_unstemmed | Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses |
| title_short | Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses |
| title_sort | different ph requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza a viruses |
| url | http://www.virologyj.com/content/4/1/39 |
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