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

• Published in: Scientific reports Vol. 6; no. 1; p. 23110
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.03.2016; Nature Publishing Group
• 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
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep23110

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.