Therapeutic and prophylactic activity of itraconazole against human rhinovirus infection in a murine model

Aeri Shim, Jae Hyoung Song, Bo Eun Kwon, Jeong Jun Lee, Jae Hee Ahn, Yeon Jeong Kim, Ki Jong Rhee, Sun Young Chang, Younggil Cha, Yong Soo Lee, Mi Na Kweon, Kwi Sung Park, Dong Eun Kim, Sungchan Cho, Hyun Jong Cho, Hyun Jeong Ko

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12 Citations (Scopus)

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.

Original languageEnglish
Article number23110
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Mar 15

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Rhinovirus
Itraconazole
Infection
Bronchoalveolar Lavage Fluid
Therapeutics
Antiviral Agents
Cholesterol
Cell Membrane
Nasal Sprays
Common Cold
Lung
Chemokines
Granulocytes
Monocytes
Vaccines
Cell Count
Cytokines
Inflammation

All Science Journal Classification (ASJC) codes

  • General

Cite this

Shim, A., Song, J. H., Kwon, B. E., Lee, J. J., Ahn, J. H., Kim, Y. J., ... Ko, H. J. (2016). Therapeutic and prophylactic activity of itraconazole against human rhinovirus infection in a murine model. Scientific reports, 6, [23110]. https://doi.org/10.1038/srep23110
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. / Therapeutic and prophylactic activity of itraconazole against human rhinovirus infection in a murine model. In: Scientific reports. 2016 ; Vol. 6.
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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.",
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Shim, A, Song, JH, Kwon, BE, Lee, JJ, Ahn, JH, Kim, YJ, Rhee, KJ, Chang, SY, Cha, Y, Lee, YS, Kweon, MN, Park, KS, Kim, DE, Cho, S, Cho, HJ & Ko, HJ 2016, 'Therapeutic and prophylactic activity of itraconazole against human rhinovirus infection in a murine model', Scientific reports, vol. 6, 23110. https://doi.org/10.1038/srep23110

Therapeutic and prophylactic activity of itraconazole against human rhinovirus infection in a murine model. / 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.

In: Scientific reports, Vol. 6, 23110, 15.03.2016.

Research output: Contribution to journalArticle

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T1 - Therapeutic and prophylactic activity of itraconazole against human rhinovirus infection in a murine model

AU - Shim, Aeri

AU - Song, Jae Hyoung

AU - Kwon, Bo Eun

AU - Lee, Jeong Jun

AU - Ahn, Jae Hee

AU - Kim, Yeon Jeong

AU - Rhee, Ki Jong

AU - Chang, Sun Young

AU - Cha, Younggil

AU - Lee, Yong Soo

AU - Kweon, Mi Na

AU - Park, Kwi Sung

AU - Kim, Dong Eun

AU - Cho, Sungchan

AU - Cho, Hyun Jong

AU - Ko, Hyun Jeong

PY - 2016/3/15

Y1 - 2016/3/15

N2 - 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.

AB - 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.

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