A Single Point Mutation Controls the Cholesterol Dependence of Semliki Forest Virus Entry and Exit

doi:10.1083/jcb.140.1.91

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© The Rockefeller University Press, 0021-9525/1998//91 $5.00
The Journal of Cell Biology, Volume 140, Number 1, , 1998 91-99

Article

A Single Point Mutation Controls the Cholesterol Dependence of Semliki Forest Virus Entry and Exit

Malini Vashishtha, Thomas Phalen, Marianne T. Marquardt, Jae S. Ryu, Alice C. Ng, and Margaret Kielian

Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461

Membrane fusion and budding are key steps in the life cycleof all enveloped viruses. Semliki Forest virus (SFV) is anenveloped alphavirus that requires cellular membrane cholesterolfor both membrane fusion and efficient exit of progeny virusfrom infected cells. We selected an SFV mutant, srf-3, thatwas strikingly independent of cholesterol for growth. This phenotypewas conferred by a single amino acid change in the E1 spikeprotein subunit, proline 226 to serine, that increased thecholesterol independence of both srf-3 fusion and exit. Thesrf-3 mutant emphasizes the relationship between the role ofcholesterol in membrane fusion and virus exit, and most significantly,identifies a novel spike protein region involved in the viruscholesterol requirement.

Abbreviations used in this paper: RT, reverse-transcriptase; SFV, Semliki Forest virus; wt, wild-type.

Address all correspondence to Margaret Kielian, Department ofCell Biology, Albert Einstein College of Medicine, 1300 MorrisPark Avenue, Bronx, New York 10461. Tel.: (718) 430-3638. Fax:(718) 430-8574. E-mail: kielian{at}aecom.yu.edu

Marianne T. Marquardt's current address is Department of Biology, Stern College, New York, NY 10016.

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