Specific Roles for Lipids in Virus Fusion and Exit Examples from the Alphaviruses - Fusion of Biological Membranes and Related Problems - page 446

tion of the virus fusion peptide? A key question is the role of specific lipids
and target membrane bilayer in the formation of the El homotrimer
structure. As part of this, it will be important to determine the potential
structural differences in the homotrimer formed in the presence of a fusion-
permissive membrane versus a fusion-inactive membrane. Increased struc-
tural information on the monomeric and trimeric forms of the El fusion
protein and the availability of virus mutants altered in their lipid require-
ments should point the way to understanding the sites and functions of
lipid-protein interaction. Our understanding of the role of cholesterol in
virus exit should become more mechanistic with advances in our knowl-
edge of virus and spike protein structures, and more molecular analysis of
the virus exit pathway. In addition, it is important for this and other virus
systems to understand the relevance of such lipid requirements to infection
of various types of cells in tissue culture, and to viral infection and patho-
genesis in animal hosts. Ultimately, a better understanding of the function
of particular lipids in virus lifecycles should enable us to design specific
strategies to interfere with their function and thus limit virus replication.
A CKNOWLEDGMENTS . We thank Dr. Sallie Glomb-Reinmund for preparing
Figure 1 and Dr. Marianne Marquardt for preparing Figure 2. The work
from our laboratory described in this review was supported by grants to
M.K. from the National Institutes of Public Health (GM 52929 and GM
57454), the American Cancer Society (RPG-93-013-07-MBC), the Hirschl
Charitable Trust, by the Jack K. and Helen B. Lazar fellowship in Cell
Biology, and by Cancer Center Core Support Grant NIH/NCI P30-
CA13330. D.L.G. was supported by an MSTP training grant from the
National Institutes of Public Health (T32 GM07288).
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