Therapeutic and prophylactic activity of itraconazole against humanrhinovirus infection in a murine model
| Autor: | Ki Jong Rhee, Yeon-Jeong Kim, Mi-Na Kweon, Aeri Shim, Jae Hyoung Song, Kwi Sung Park, Dong-Eun Kim, Yong-Soo Lee, Hyun-Jeong Ko, Younggil Cha, Bo Eun Kwon, Jeong-Jun Lee, Sungchan Cho, Hyun-Jong Cho, Sun Young Chang, Jae Hee Ahn |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Chemokine Rhinovirus medicine.medical_treatment 030106 microbiology Inflammation Pharmacology Virus Replication medicine.disease_cause Antiviral Agents Article 03 medical and health sciences Immune system medicine Animals Cytotoxicity Lung Mice Inbred BALB C Picornaviridae Infections Multidisciplinary medicine.diagnostic_test biology Cell Membrane Cholesterol 030104 developmental biology Bronchoalveolar lavage Cytokine Viral replication Immunology biology.protein Cytokines Female Itraconazole medicine.symptom Bronchoalveolar Lavage Fluid |
| Zdroj: | SCIENTIFIC REPORTS(6) Scientific Reports |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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