HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Simon, M. Articles by Mirazimi, A. Search for Related Content PubMed PubMed Citation Articles by Simon, M. Articles by Mirazimi, A. Agricola Articles by Simon, M. Articles by Mirazimi, A.

Crimean-Congo hemorrhagic fever virus entry and replication is clathrin-, pH- and cholesterol-dependent

¹ Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden
² Centre for Microbiological Preparedness, Swedish Institute for Infectious Disease Control, S-171 82 Solna, Sweden

Correspondence
Ali Mirazimi
ali.mirazimi{at}smi.se

To date, the entry pathway and replication mechanisms for members of the family Bunyaviridae, and especially for Crimean-Congo hemorrhagic fever virus (CCHFV), are poorly understood. Considering the severity of disease and the widespread geographical occurrence of CCHFV, investigating viral entry is of great value for development of antivirals. In this study, we have shown that knockdown of clathrin by small interfering RNA significantly reduced CCHFV nucleocapsid protein and viral RNA levels, suggesting that CCHFV utilizes clathrin-dependent endocytosis. In contrast, caveolin-1, an important constituent of caveolae endocytosis, is not important in CCHFV infection. Moreover, treatment with drugs that are known to interfere with the formation of clathrin-coated pits (sucrose and chlorpromazine) or endosome acidification (bafilomycin A1 and NH₄Cl) also supported a clathrin-dependent pathway in the entry process of CCHFV. Finally, we demonstrated that cholesterol depletion in the cell plasma membrane significantly inhibited CCHFV infection. In the presence of exogenous cholesterol, this process was reversed, suggesting that cholesterol is important in the life cycle of CCHFV.