Hantaan virus enters cells by clathrin-dependent receptor-mediated endocytosis.
The cellular entry of Hantaan virus (HTN) occurs through interactions with beta(3) 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.
Jin
Mirim
M
Division of Life Science and Graduate School of Biotechnology, Korea University, 1, 5-ka, Anam-Dong, Sungbuk-Gu, Seoul 136-701, Korea.
Park
Junghyun
J
Lee
Sungwook
S
Park
Boyoun
B
Shin
Jinwook
J
Song
Ki-Joon
KJ
Ahn
Tae-In
TI
Hwang
Sue-Yun
SY
Ahn
Byung-Yoon
BY
Ahn
Kwangseog
K
D000818:Animals; D021941:Caveolae / Q000502:physiology*; D002522:Chlorocebus aethiops; D002966:Clathrin / Q000378:metabolism*; D034281:Dynamins; D004705:Endocytosis / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000502:physiology; D018063:Hantaan virus / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014709:Vero Cells
D002966:Clathrin; D011956:Receptors, Cell Surface; D020558:GTP Phosphohydrolases; D034281:Dynamins