The cellular entry of Hantaan virus (HTN) occurs through interactions with β3 integrins as cellular receptors. However, the process of HTN infection following attachment to the cell surface is not well understood. Our data indicate that overexpression of a dominant-negative mutant dynamin inhibits HTN internalization and that compounds that block clathrin- but not caveolae-dependent endocytosis also reduce HTN infectivity. In addition, we show that HTN colocalizes with the clathrin heavy chain but not with caveolae. At the early phase of infection HTN colocalizes with EEA-1, an early endosome marker, and later, HTN colocalizes with LAMP-1, a lysosome marker. Cells treated with lysosomotropic agents are largely resistant to infection, suggesting that a low-pH-dependent step is required for HTN infection. These findings demonstrate that HTN enters cells via the clathrin-coated pit pathway and uses low-pH-dependent intracellular compartments for infectious entry.
Bibliographical noteFunding Information:
This work was supported by a grant from KOSEF (R01-1999-00143). We thank S. Schmid , Harald Stenmark, and the Developmental Stud ies Hybridoma Bank at the University of Iowa for the generous gift of cell lines and antibod ies.
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