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microdomains, where lipid molecules reside in lo phase or lo-like phase. 3
Simons and Ikonen showed that these microdomains incorporate spe-
cific membrane proteins, such as glycosyl-phosphatidyl-inositol (GPI)-
anchored proteins and doubly acylated tyrosine kinases of the Src family,
and that they play crucial roles in membrane functions, such as mem-
brane trafficking and signal transduction. 2 It was postulated that these
microdomains move around the plane of cell membranes accommodat-
ing selected membrane proteins and that they function as communica-
tion centers of membrane proteins; hence, these microdomains were
termed as moving platforms or functional rafts. 2 Because of the dynamic
properties and the small size of the microdomains, it has been difficult
to obtain direct evidence of their existence in living cells. However, data
from a fluorescence resonance energy transfer technique and a cross-
linking method strongly suggested that lipid microdomains do exist in
living cells. 5-7 When studying these raft microdomains, it should be kept
in mind that they are dynamic structures that continuously change in
terms of size, shape, and proteins incorporated.
Lipid Rafts and Viruses
Viruses are obligate parasites of living organisms and their replication
is absolutely dependent on the host cell machinery. It is now widely
accepted that membrane lipids can control protein transport and reg-
ulate interaction of intracellular, extracellular, and membrane pro-
teins by forming dynamic lipid microdomains. These properties of
membrane lipids are thought to be fundamental for eukaryotic cells,
and many cellular and viral membrane proteins appear to serve the
function of specifying interactions with membrane lipids. Viruses
that have been shown to use lipid microdomains are listed in Table 1.
The number of such viruses is increasing, and ultimately most
enveloped viruses might be included in this list. 8-12 It will be impor-
tant to learn how these viruses use lipid microdomains in their repli-
cation cycles. Influenza A virus (influenza virus) is the best-studied
example of the use of lipid rafts by a virus. In this review we discuss
how influenza virus uses lipid microdomain rafts to promote its
replication cycles.
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