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These data therefore suggest that raft-association is not obligatory for
the apical transport of influenza virus glycoproteins and that influenza
virus can use other cellular machinery or microdomains to transport
HA and NA to the apical cell surface. Another raft-like lipid micro-
domain may regulate the transport of influenza virus glycoproteins.
M1 is a peripheral membrane protein and plays a central role in
virus assembly and budding.
28
M1 is most abundant in virions and
thought to interact with both inside ribonucleoprotein (RNP) cores
and outside envelope glycoproteins, HA and NA
29-31
(Fig. 2A). When
M1 was expressed alone, only a small amount of M1 associated with
rafts.
17,19,30
However, the amount of M1 isolated from raft membrane
fractions increased significantly by co-expressing HA and NA.
17,19,29,30
M2 is the third integral membrane protein and functions as a proton
ion channel required for virus uncoating.
13
M2 is transported selec-
tively to apical cell membranes, like HA and NA.
32
However, no sig-
nificant association with rafts was shown, unlike HA and NA.
17,19
These data may explain inefficient incorporation of M2 into virions.
19,33
Recently, Carrasco
et al
. showed that nucleoprotein (NP), the major
component of RNP, was also transported to apical cell membranes
and that this apical transport was raft-dependent.
34
Raft-Association of Viral Glycoproteins Promotes
Influenza Virus Replication
As stated above, influenza virus HA has three palmitoylated cystein
residues. These cysteins were shown to be needed for HA raft-
association. However, a recombinant influenza virus having a mutated
HA, where the three cysteins were substituted with other residues,
could be generated by a revere genetics method and was shown to be
viable.
35
This observation may suggest that the raft-associating prop-
erty of HA is not so important for influenza virus replication. To
address this issue, nine recombinant influenza viruses have been gen-
erated whose HA proteins contained a series of alanine substitutions
at their TM domains.
17
All mutated HAs were transported to and
expressed on the cell surface as efficiently as the wild-type (wt) HA,
but they differed in their ability to associate with rafts. Some of them
