1968 Virology_ Coronaviruses.pdf

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NATURE,
VOL.
220.
NOVEMBER
16.
1968
but not 50s subunits is t,he same as in wild t,ype strains.
In other words, it is the
30s
subunits and other com-
ponents necessary for initiation and not the
708
ribosome which affect mRNA synthesis.
GENE
CONTROL
Histones-Animal and Vegetable
from our Molecular Biology Correspondent
other of isoleucine for valine; in addition lys-20 is
not methylated in the pea protein. Apart from this
astonishing evolutionary conservation of sequence-
a phenomenon altogether unique among the yery
considerable number of known sequences in a range of
proteins of the most diverse functions-this result
points ineluctably to some highly specific and precisely
defined biochemical function for the histone.
VIROLOGY
THE biochemical world has long been divided on the
question of whether the histones are actively involved
in suppression and activation of genes, or whether thcy
exist as essentially passive-a<nd thcreforc, according to
one view, slightly dreary-packaging materials. Among
the indications that the role of the histones is not
purely passive are the many observations of the
enzymic modification of certain of their side chains
under circumstances which suggest that this may
somehow be involved in the control of transcription
of the DNA. The attachment of acetyl groups to the
N-termini of two of the histones, and of methyl and
phosphoryl groups to side chains of others, has been
demonstrated. Allfrey and his co-workers found that
whereas some of these modifying groups remain more
or less permanently bound, others are metabolically
active, in the sense that a radioactive precursor is
rapidly incorporated a t thcsc points.
Gershey, Vidali and Allfrey
(J.
Biol.
Chem.,
243,
5018; 1968) have now found, from experiments in-
volving pulse-labelling of calf thymus nuclei with
'%-acetate, that the histone component f2al exhibits
this type of rapid turnover. Moreover, proteolytic
digestion of the histone and separation of the fragments
led to the identification of the label in a single E-acetyl-
lysine residue. This is therefore the metabolically
active site. Rapid labelling also occurs in the arginine-
rich fraction,
f 3 .
Meanwhile, in
E. L.
Smith's laboratory in Los
Angeles, the latter protein (also termed histone-IV
in another system of nomenclature) has been completely
sequenced, and the modified side chain located. This
work, reported a t the autumn meeting of the National
Academy of Sciences, must surely be expected to
stimulate a wide resurgence of interest in the histone
field. The protein has 102 residues, the rapidly
labelled site being lys-16. I n the protein, as
isolated,
this residue is acetylated in half the molecules. There
is also a fully methylated lysine a t position 20, the
remaining nine lysincs being unmodified. The sequence
shows some curious features-in particular a marked
polarization of chargc, such that the N-terminal end
contains a predominance of the positive group.9, and
the other end most of the negative and hydrophobic
side chains. This suggests that the attachment to
DNA may primarily involve one end of the molccule,
perhaps leaving the other free to engage in some
function which is as yet unknown.
Thc same workers (Delange, Fambrough, Smith and
Bonner) also prepared the corresponding histone
fraction from pca secdlings-an operation involving
germination of no less than 20 tons of seeds-and now
have the substantially complete sequence. An early
report, in which the first 19 residues from the C-terminal
end were found to be identical in the pea and calf
thymus proteins, is borne out. Indeed, it appears
that the chains are identical in length, and differ only
by two replacements, one of arginine for lysine, the
A
NEW
group of viruses with the name of coronaviruses
has been recognized by an informal group of virologists
who have sent their conclusions to
Nature.
(They are
J.
D.
Almeida;
D.
M. Berry; C.
H.
Cunningham;
D. Hamre;
M.
S. Hofstad;
L.
Mallucci;
K.
McIntosh;
D.
A.
J.
Tyrrell.)
They point out that with negative staining, avian
infectious bronchitis virus has a characteristic electron
microscopic appearance resembling, but distinct from,
that of myxoviruses. Particles are more or less rounded
in profile; although there is a certain amount of poly-
morphism, there is also a characteristic "fringe" of pro-
jections 200
A
long, which are rounded or petal shaped,
rather than sharp or pointed, as in the myxoviruses.
This appearance, recalling the solar corona, is s h a r d
by mouse hepatitis virus and several viruses recently
recovered from man, namely strain B814, 229E and
several others. These viruses also share a number of
other properties as indicated in the table. (Anyone
interested in the data on which the table is based may
obtain a short bibliography on application to Dr
D.
A.
J.
Tyrrell a t the Common Cold Research Unit,
Salisbury, Wiltshire.)
PROPERTIES
O F
THESE
VIRCSES
Avian
infectious Mouse
Humnn
bronchitis hepatitis strains
Size. Filtration
80-1 20 m p
89
mp
Electron microscopy* 80-120 rnp 100 m p
80--160
mp
Charactcristia surface structure
Essential lipid (ether lability)
Apparent ribonucleic acid content
(unsusceptibility to DNA inhibitors)
Dcnsity of infectious unit
1.18
?
1.19
Replication in cytoplasmic vesicles
4-
*
Negative contrast
technique-projections
are included in
the diameter
of
the particlc.
+
+
+
+
+
+
+
+
+
+
+
Some other relevant properties should bc mentioned.
There is an antigenic relationship between the human
and murinc strains, but none has been detected between
avian strains and the others. A haemagglutinin has
been detccted by certain workers using avian infectious
bronchitis virus and also antigens separable from the
virus particle, but these have so far not been recorded
for the human or murine strains.
I n the opinion of the eight virologists thcse viruses
are members of a previously unrecognized group which
they suggest should be called the coronaviruses, to
recall the characteristic appearance by which these
viruses are identified in the elecbron microscope.
These suggestions have been received by members of
the Myxovirus Study Group (chairman, Professor
A.
P.
Waterson) under the International Committee for the
Nomenclature of Viruses (ICNV). Thc suggestions
were found acceptable and are now t o be considered by
the Vertebrate Virus Committee of the ICNV.

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