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BIOGRAPHY:
Dr. López received her Ph.D. in Virology from the National
Autonomous University of Mexico in 1986. From 1989 to 1993, she was
Assistant Professor of Molecular Biology at the Center for Research on
Genetic Engineering and Biotechnology in Cuernavaca, Mexico. From 1992
to 1993 she was a Fogarty Fellow in the Biology Department of the
California Institute of Technology. In 1994 she received the National
Science Award from the Mexican Academy of Sciences, in 2001 UNESCO's
Carlos J. Finlay Prize for Microbiology, in 2002 the Biennial Prize in
Gastrointestinal Diseases from the Fundación Mexicana para la
Salud, and in 2004 the National University of Mexico awarded her the
second "Sor Juana Ines de la Cruz" Medal, which honors the University's
most outstanding female scientist. She is currently Professor of the
Genetics and Molecular Physiology Department of the Institute of
Biotechnology, National Autonomous University of Mexico. Her
HHMI-funded project involves the molecular characterization of the
interactions of rotavirus with its host cell.
RESEARCH ABSTRACT SUMMARY:
Rotavirus Enters the Cell Through a Non-Clathrin–,
Non-Caveolin–Dependent Mechanism
Rotaviruses are the single most important cause of severe diarrhea
in the young of many animal species. While we have recently learned
much about the viral and cellular proteins involved in the initial
attachment of rotaviruses to their host cells, the mechanism through
which these viruses reach the cell cytoplasm is poorly understood.
Here, we report our studies on the effect on rotavirus cell infection
of drugs and dominant negative mutations known to impair
clathrin-mediated endocytosis and caveolae-mediated endocytosis.
Rotaviruses were able to enter cells in the presence of compounds that
inhibit the clathrin-mediated endocytosis, as well as cells overexpressing a dominant negative form of Eps15, a protein crucial
for the assembly of clathrin coats. We also found that rotavirus was
able to infect cells in which uptake by caveolae was blocked;
furthermore, treatment with the cholesterol-binding agents nystatin and
filipin, as well as transfection of cells with dominant negative
caveolin-1 and caveolin-3 mutations, or with a short interfering siRNA
to caveolin-1, which silenced the expression of this protein, had no
effect on rotavirus infection. Interestingly, cells treated with
methyl-betacyclodextrin, a drug that sequesters cholesterol from
membranes, and cells expressing a dominant negative mutation of the
large GTPase dynamin, a protein known to function in several membrane
scission events, were not infected by rotavirus, indicating that
cholesterol and dynamin play a role in the entry of rotaviruses. Taken
together, our results suggest that rotaviruses infect cells by a
recently described non-clathrin–, non-caveolin–dependent pathway. The roles of cholesterol and dynamin during viral entry are currently under
investigation.
Photo: Kent Kallberg, Kallberg Studios
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