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BIOCHEMICAL SOCIETY TRANSACTIONS
Structure of Influenza Virus
NICHOLAS G. WRIGLEY and JOHN J. SKEHEL
Divisions of Biophysics and Virology, National Institute for Medical Research,
Mill Hill, London NW7 l A A , U.K.
Electron-microscopic and chemical studies of the influenza virus and its components
have indicated the following.
(1) The virus consists of an RNA genome in association with several types of protein
enclosed within a lipoprotein envelope. In the electron microscope the particles appear
rounded, about lOOnm (1000A) in diameter with a fringe of spikes projecting from the
surface. Occasionally a coiled internal structure is also visible.
(2) All influenza viruses grown in chick-embryo cells contain seven types of polypeptide. These range in moIecular weight from 94000 to 25000 and are present in unequal proportions, e.g. the smallest polypeptide accounts for 30% of the total virus
protein whereas the largest accounts for only 1 %.
l o v 3 x Molecular
Location
weight
94
PI
Internal
83
P2
Internal
65
NA
Envelope glycoprotein (neuraminidare)
H A I Envelope glycoprotein (haemagglutinin)
NP
Nucleoprotein (internal)
I
If
H A 2 Envelope glycoprotein (haemagglutinin)
MP
28
15
M a t r i x p r o t e i n (internal)
Fig. 1. Diagram of the seven polypeptide components of influenzavirus separatedby sodium
dodecyl sulphate-polyacrylamide-gelelectrophoresis
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548th MEETING, BELFAST
(3) The location of the polypeptides of each species within the virus particle is as
follows. (a) Three types of polypeptide are present in the lipoprotein envelope; two are
components of a haemagglutinin and the other is the subunit of a neuraminidase. All
three of these polypeptides are glycosylated. (b) The remaining four non-glycosylated
polypeptides are internal to the lipid bilayer and are invariant in molecular weight from
strain to strain of virus. One of these of molecular weight 53000 is the subunit of the
nucleocapsid and is associated with the virus RNA. The other major internal component
has a molecular weight of 25000 and is called the matrix protein since it appears to fill
the core of the virus particle. Both of these proteins have been shown to be type-specific
antigens. The remaining two polypeptides are the largest in the virion with molecular
weights of 94000 and 83000, but since together they represent less than 2 % of the mass of
the particle details of their structural roles or their function are not presently known.
(4) The size and shape of both the haemagglutinin and the neuraminidase have been
anatysed in some detail. They can be isolated by a variety of procedures which mainly
involve either proteolysis or detergent disruption of purified viruses. The haemagglutinin
has a molecular weight of about 210 000 and contains either two or three of each glycopolypeptide component, HA, and HA2 (Fig. l ) which have apparent molecular weights
of 58000 and 28000 respectively. In the electron microscope it appears as a rod-shaped
molecule about 15nm (150A)long and 5nm (50A)wide and looks triangular when seen
in end view. This latter observation is consistent with the proposition that three molecules of each type of glycopolypeptide are present in the native glycoprotein. The
neuraminidase is a mushroom-shaped molecule and, like the haemagglutinin, aggregates to form rosettes in the absence of detergents. The part of the molecule responsible
for this aggregation appears to be the proximal end of the almost invisible ‘stalk’ which,
together with the ability to aggregate, is lost after protease digestion. The remaining
‘head’ portion is about 8 x 8nm (80x 80A) square and 4nm (40& thick and appears to
consist of four subunits. This is consistent with the estimates of the molecular weight of
the ‘head‘ of about 200000 and of its constituent glycopolypeptides of about 50000.
(5) In the intact virus particle the haemagglutinin and the neuraminidase are present in
variable proportions ranging from 5 :1 to 1 :1 . In the electron microscope they are difficult to distinguish from each other on the virus, but a depleted fringe ofspikes isclearly
seen after selective removal of the haemagglutinin by limited bromelain digestion.
(6) After extensive proteolysis smoothly rounded particles are obtained which are
shorn of their spikes but have the lipid bilayer of the membrane and the internal components intact. In comparison removal of the envelope with detergents leaves rounded but
amorphous-looking cores which also contain the four internal polypeptides.
Assembly and Functions of Viral Membranes
PURNELL W. CHOPPIN
The Rockefeller University, New York, N. Y. 10021, U.S.A.
Several of the major groups of animal viruses are enveloped in a membrane which is
acquired at the surface of the host cell as the virus is assembled during a budding process
from the plasma membrane. Our laboratory has studied the structure, replication and
interactions with cell membranes of two groups of enveloped RNA viruses, myxoviruses
and paramyxoviruses. The myxovirus group consists of the various types of influenza
virus, and the large paramyxovirus group includes parainfluenza viruses, such as SV5,
Sendai, Newcastle-disease, mumps and measles viruses. These viruses cause a wide
variety of diseases of man and animals, ranging from mild respiratory illnesses to
chronic neurological diseases.
In addition to the biological importance of these viruses as etiological agents of
disease, they also serve as models for studies of the structure and assembly of membranes.
Membrane-enclosed viruses have several properties which make them useful for such
studies.
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