Therapeutic and prophylactic activity of itraconazole against human rhinovirus infection in a murine model
Human rhinovirus (HRV) is the most common viral infectious agent in humans and is the predominant cause of the common cold. There is a need for appropriate vaccines or therapeutic agents to treat HRV infection. In this study, we investigated whether itraconazole (ICZ) can protect cells from HRV-indu...
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| creator | Shim, Aeri Song, Jae-Hyoung Kwon, Bo-Eun Lee, Jeong-Jun Ahn, Jae-Hee Kim, Yeon-Jeong Rhee, Ki-Jong Chang, Sun-Young Cha, Younggil Lee, Yong-Soo Kweon, Mi-Na Park, Kwi Sung Kim, Dong-Eun Cho, Sungchan Cho, Hyun-Jong Ko, Hyun-Jeong |
| description | Human rhinovirus (HRV) is the most common viral infectious agent in humans and is the predominant cause of the common cold. There is a need for appropriate vaccines or therapeutic agents to treat HRV infection. In this study, we investigated whether itraconazole (ICZ) can protect cells from HRV-induced cytotoxicity. Replication of HRV1B was reduced by ICZ treatment in the lungs of HRV1B- as compared to vehicle-treated mice. The numbers of immune cells, including granulocytes and monocytes, were reduced in bronchoalveolar lavage fluid (BALF) by ICZ administration after HRV1B infection, corresponding to decreased pro-inflammatory cytokine and chemokine levels in BALF. A histological analysis of lung tissue showed that ICZ suppressed inflammation caused by HRV1B infection. Interestingly, pretreatment of mice with ICZ in the form of a nasal spray had potent prophylactic antiviral activity. Cholesterol accumulation in the plasma membrane was observed upon HRV infection; ICZ blocked cholesterol trafficking to the plasma membrane, as well as resulted in its accumulation in subcellular compartments near the nucleus. These findings suggest that ICZ is a potential antiviral agent for the treatment of HRV infection, which can be adopted preventatively as well as therapeutically. |
| doi_str_mv | 10.1038/srep23110 |
| format | Article |
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There is a need for appropriate vaccines or therapeutic agents to treat HRV infection. In this study, we investigated whether itraconazole (ICZ) can protect cells from HRV-induced cytotoxicity. Replication of HRV1B was reduced by ICZ treatment in the lungs of HRV1B- as compared to vehicle-treated mice. The numbers of immune cells, including granulocytes and monocytes, were reduced in bronchoalveolar lavage fluid (BALF) by ICZ administration after HRV1B infection, corresponding to decreased pro-inflammatory cytokine and chemokine levels in BALF. A histological analysis of lung tissue showed that ICZ suppressed inflammation caused by HRV1B infection. Interestingly, pretreatment of mice with ICZ in the form of a nasal spray had potent prophylactic antiviral activity. Cholesterol accumulation in the plasma membrane was observed upon HRV infection; ICZ blocked cholesterol trafficking to the plasma membrane, as well as resulted in its accumulation in subcellular compartments near the nucleus. These findings suggest that ICZ is a potential antiviral agent for the treatment of HRV infection, which can be adopted preventatively as well as therapeutically.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep23110</identifier><identifier>PMID: 26976677</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/106 ; 13/31 ; 45/77 ; 631/250/255/2514 ; 631/326/596/1296 ; 64/60 ; Alveoli ; Animal models ; Animals ; Antifungal agents ; Antiviral activity ; Antiviral Agents - pharmacology ; Antiviral Agents - therapeutic use ; Bronchoalveolar Lavage Fluid - chemistry ; Bronchoalveolar Lavage Fluid - cytology ; Bronchus ; Cell Membrane - metabolism ; Cholesterol ; Cholesterol - metabolism ; Common cold ; Cytokines - metabolism ; Cytotoxicity ; Female ; Humanities and Social Sciences ; Infections ; Inflammation ; Itraconazole ; Itraconazole - pharmacology ; Itraconazole - therapeutic use ; Leukocytes (granulocytic) ; Lung - virology ; Membrane trafficking ; Mice, Inbred BALB C ; Monocytes ; multidisciplinary ; Nuclei ; Picornaviridae Infections - drug therapy ; Picornaviridae Infections - prevention & control ; Picornaviridae Infections - virology ; Rhinovirus ; Rhinovirus - drug effects ; Rhinovirus - physiology ; Rodents ; Science ; Virus Replication</subject><ispartof>Scientific reports, 2016-03, Vol.6 (1), p.23110-23110, Article 23110</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Mar 2016</rights><rights>Copyright © 2016, Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-c14425abf4b382b66ac8bfdedb672fed53343dd84fca1198617d7255c783090f3</citedby><cites>FETCH-LOGICAL-c438t-c14425abf4b382b66ac8bfdedb672fed53343dd84fca1198617d7255c783090f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791555/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791555/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,41099,42168,51554,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26976677$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shim, Aeri</creatorcontrib><creatorcontrib>Song, Jae-Hyoung</creatorcontrib><creatorcontrib>Kwon, Bo-Eun</creatorcontrib><creatorcontrib>Lee, Jeong-Jun</creatorcontrib><creatorcontrib>Ahn, Jae-Hee</creatorcontrib><creatorcontrib>Kim, Yeon-Jeong</creatorcontrib><creatorcontrib>Rhee, Ki-Jong</creatorcontrib><creatorcontrib>Chang, Sun-Young</creatorcontrib><creatorcontrib>Cha, Younggil</creatorcontrib><creatorcontrib>Lee, Yong-Soo</creatorcontrib><creatorcontrib>Kweon, Mi-Na</creatorcontrib><creatorcontrib>Park, Kwi Sung</creatorcontrib><creatorcontrib>Kim, Dong-Eun</creatorcontrib><creatorcontrib>Cho, Sungchan</creatorcontrib><creatorcontrib>Cho, Hyun-Jong</creatorcontrib><creatorcontrib>Ko, Hyun-Jeong</creatorcontrib><title>Therapeutic and prophylactic activity of itraconazole against human rhinovirus infection in a murine model</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Human rhinovirus (HRV) is the most common viral infectious agent in humans and is the predominant cause of the common cold. There is a need for appropriate vaccines or therapeutic agents to treat HRV infection. In this study, we investigated whether itraconazole (ICZ) can protect cells from HRV-induced cytotoxicity. Replication of HRV1B was reduced by ICZ treatment in the lungs of HRV1B- as compared to vehicle-treated mice. The numbers of immune cells, including granulocytes and monocytes, were reduced in bronchoalveolar lavage fluid (BALF) by ICZ administration after HRV1B infection, corresponding to decreased pro-inflammatory cytokine and chemokine levels in BALF. A histological analysis of lung tissue showed that ICZ suppressed inflammation caused by HRV1B infection. Interestingly, pretreatment of mice with ICZ in the form of a nasal spray had potent prophylactic antiviral activity. Cholesterol accumulation in the plasma membrane was observed upon HRV infection; ICZ blocked cholesterol trafficking to the plasma membrane, as well as resulted in its accumulation in subcellular compartments near the nucleus. These findings suggest that ICZ is a potential antiviral agent for the treatment of HRV infection, which can be adopted preventatively as well as therapeutically.</description><subject>13/106</subject><subject>13/31</subject><subject>45/77</subject><subject>631/250/255/2514</subject><subject>631/326/596/1296</subject><subject>64/60</subject><subject>Alveoli</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antifungal agents</subject><subject>Antiviral activity</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Bronchoalveolar Lavage Fluid - chemistry</subject><subject>Bronchoalveolar Lavage Fluid - cytology</subject><subject>Bronchus</subject><subject>Cell Membrane - metabolism</subject><subject>Cholesterol</subject><subject>Cholesterol - metabolism</subject><subject>Common cold</subject><subject>Cytokines - metabolism</subject><subject>Cytotoxicity</subject><subject>Female</subject><subject>Humanities and Social Sciences</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Itraconazole</subject><subject>Itraconazole - 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drug effects</topic><topic>Rhinovirus - physiology</topic><topic>Rodents</topic><topic>Science</topic><topic>Virus Replication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shim, Aeri</creatorcontrib><creatorcontrib>Song, Jae-Hyoung</creatorcontrib><creatorcontrib>Kwon, Bo-Eun</creatorcontrib><creatorcontrib>Lee, Jeong-Jun</creatorcontrib><creatorcontrib>Ahn, Jae-Hee</creatorcontrib><creatorcontrib>Kim, Yeon-Jeong</creatorcontrib><creatorcontrib>Rhee, Ki-Jong</creatorcontrib><creatorcontrib>Chang, Sun-Young</creatorcontrib><creatorcontrib>Cha, Younggil</creatorcontrib><creatorcontrib>Lee, Yong-Soo</creatorcontrib><creatorcontrib>Kweon, Mi-Na</creatorcontrib><creatorcontrib>Park, Kwi Sung</creatorcontrib><creatorcontrib>Kim, Dong-Eun</creatorcontrib><creatorcontrib>Cho, Sungchan</creatorcontrib><creatorcontrib>Cho, Hyun-Jong</creatorcontrib><creatorcontrib>Ko, Hyun-Jeong</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shim, Aeri</au><au>Song, Jae-Hyoung</au><au>Kwon, Bo-Eun</au><au>Lee, Jeong-Jun</au><au>Ahn, Jae-Hee</au><au>Kim, Yeon-Jeong</au><au>Rhee, Ki-Jong</au><au>Chang, Sun-Young</au><au>Cha, Younggil</au><au>Lee, Yong-Soo</au><au>Kweon, Mi-Na</au><au>Park, Kwi Sung</au><au>Kim, Dong-Eun</au><au>Cho, Sungchan</au><au>Cho, Hyun-Jong</au><au>Ko, Hyun-Jeong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Therapeutic and prophylactic activity of itraconazole against human rhinovirus infection in a murine model</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-03-15</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>23110</spage><epage>23110</epage><pages>23110-23110</pages><artnum>23110</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Human rhinovirus (HRV) is the most common viral infectious agent in humans and is the predominant cause of the common cold. There is a need for appropriate vaccines or therapeutic agents to treat HRV infection. In this study, we investigated whether itraconazole (ICZ) can protect cells from HRV-induced cytotoxicity. Replication of HRV1B was reduced by ICZ treatment in the lungs of HRV1B- as compared to vehicle-treated mice. The numbers of immune cells, including granulocytes and monocytes, were reduced in bronchoalveolar lavage fluid (BALF) by ICZ administration after HRV1B infection, corresponding to decreased pro-inflammatory cytokine and chemokine levels in BALF. A histological analysis of lung tissue showed that ICZ suppressed inflammation caused by HRV1B infection. Interestingly, pretreatment of mice with ICZ in the form of a nasal spray had potent prophylactic antiviral activity. Cholesterol accumulation in the plasma membrane was observed upon HRV infection; ICZ blocked cholesterol trafficking to the plasma membrane, as well as resulted in its accumulation in subcellular compartments near the nucleus. These findings suggest that ICZ is a potential antiviral agent for the treatment of HRV infection, which can be adopted preventatively as well as therapeutically.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26976677</pmid><doi>10.1038/srep23110</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/106 13/31 45/77 631/250/255/2514 631/326/596/1296 64/60 Alveoli Animal models Animals Antifungal agents Antiviral activity Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Bronchoalveolar Lavage Fluid - chemistry Bronchoalveolar Lavage Fluid - cytology Bronchus Cell Membrane - metabolism Cholesterol Cholesterol - metabolism Common cold Cytokines - metabolism Cytotoxicity Female Humanities and Social Sciences Infections Inflammation Itraconazole Itraconazole - pharmacology Itraconazole - therapeutic use Leukocytes (granulocytic) Lung - virology Membrane trafficking Mice, Inbred BALB C Monocytes multidisciplinary Nuclei Picornaviridae Infections - drug therapy Picornaviridae Infections - prevention & control Picornaviridae Infections - virology Rhinovirus Rhinovirus - drug effects Rhinovirus - physiology Rodents Science Virus Replication |
| title | Therapeutic and prophylactic activity of itraconazole against human rhinovirus infection in a murine model |
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