Biology Reference
In-Depth Information
and sphingolipids.
19
When affinity of HA or NA with rafts was low-
ered by mutagenesis, the virus contained a reduced amount of HA
and NA, respectively.
17,36
A decrease in the number of HA spikes in a
nonraft HA virus was compensated for by an increase in the number
of NA spikes that associated with rafts.
17
Considering these data
together, we can illustrate the assembly process of influenza virus as
follows (Fig. 2B). Envelope glycoproteins associate with rafts at the
Golgi apparatus.
17,47
This association seems to be required for NA to
gain maximum enzyme activity and be efficiently transported to the
cell surface.
36
During cell surface transport, both HA and NA are
concentrated in the microdomain rafts, whereas M2 ion channel pro-
teins are largely excluded from the rafts.
17,19
At the plasma membrane,
CTs of HA and NA concentrated in the microdomain rafts function
as docks for M1,
29,30
which is the major driving force of virus bud-
ding.
28
Consequently, these raft regions act as the assembly sites of
budding viruses.
23
M1 proteins are thought to interact with both CTs of
glycoproteins and NP, a major constituent of RNP cores. M1 can thus
drag RNP cores into the assembly sites. The intrinsic raft-associating
property of NP may also contribute to transport of RNPs to assembly
sites.
34
Dragged RNP cores further promote the budding process.
Finally, the budding viruses are enveloped with the raft-containing
membranes with tightly packed viral glycoproteins that allow the
viruses to initiate the next round of infections efficiently.
17
Concluding Remarks
Lipid molecules of biological membranes have been thought to func-
tion as a simple solvent of membrane proteins. Now, it is recognized
that these molecules form multi-functional microdomains. The possi-
bility that these microdomains function in an important way to allow
concentration of selected biological components within membranes
has made them an attractive focus of study for many cell biologists,
immunologists, and virologists. Lipid microdomain rafts are generally
isolated as detergent-insoluble membrane fractions. However, direct
evidence of the existence of these microdomains in living cells has
been difficult to obtain, raising some skepticism as to their existence.
48
