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Characterization of the interferon- and virus-inducible Mx promoter
97 CHARACTERIZATION
OF THE INTERFERON- AND VIRUS-INDUCIBLE
Hubert Hug, Luigi Bazzigher’, Weissmann.
llnstitut
lnstitut
fi.ir lmmunoiogie
The interferon that selectively
Maria Costas,
(IFN)-regulated
of influenza
over at least 55 kb of DNA.
non-coding
sequence
maximal
by IFN-a/8
virus.
is about
Zurich,
Zurich
of 14 exons,
and the first exon, comprising
of the promoter
140 bp upstream
is present in the Mx promoter
promoters
characterized
to date.
Newcastle
disease virus (NDV) as by IFN.
the Mx gene by virus is detectable
The Mx gene consists
to the IFN response.
PuGAAANt-2GA~PyPy
that this induction
CH-8093
CH-8028
a
by an intron of >30 kb from the second exon,
The 5’ boundary
At least two distinct regions contribute
possibility
Zgrich,
Zurich,
The Mx promoter
of 29 bp, are separated
the initiation codon.
induction
1, Un~versit~t
Universitat
and Charles
Mx gene of the mouse encodes the 72 kD nuclear Mx protein
inhibits the replication
distributed
which contains
Markus Aebi, Peter Staeheli*
fijr Moiekularbiologie und Virologie,
Mx PROMOTER
Surprisingly,
of the transcription A consensus
for
initiation
site.
sequence of the type
as well as in all other IFN-inducible
the Mx promoter
In cells with blocked
is induced
IFN.
other viruses besides NDV act as inducers of IFN-res~nsive
as efficiently
protein synthesis,
as early as 90 min after infection,
occurs via virus-induced
region required
virtually
excluding
We are now testing
by
induction
of
the
whether
genes.
98 ANTIe~IC ISOLATED
AND MOLECU~ FROM AN INFECTED
V~IATION INDIVIDUAL
IN SU~POPU~TIONS OF INFLUENZA IN DIFFERENT HOST CELLS
VIRUSES
JACQUELINE M. KATZ. MAOLIANG WANG, JAMES C PAULSON* AND ROBERT G. WEBSTER Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, 332 North Lauderdale, P.O. Box 318, Memphis, TN 38101 and *Department of Biological Chemistry, UCLA School of Medicine, Los Angeles, CA 90024. Influenza viruses grown in embryonated chicken eggs frequently possess antigenically and structurally distinguishable hemagglutinin (HA) compared to To investigate virus from the same source grown in mammalian cell culture. the extent of variation in the virus population which can be isolated from a single infected individual, viruses were isolated at limiting dilution from an original throat wash sample in eggs or mammalian MDCK cells, and the and receptor-binding properties of their HA molecules antigenic, structural The HA of virus clones isolated in MDCK cells were were determined. In contrast, viruses from the same antigenically and structurally identical. of three antigenic and structurally source isolated in eggs, consisted Amino acid substitutions in the HA of egg-grown distinct subpopulations. variants were clustered around the receptor-binding site of the molecule. One egg-grown variant population, possessing a single amino acid substitution altered receptor-binding properties as in antigenic site A, displayed to inhibition by non-immune horse serum and a indicated by resistance sialic acid (SA) 2,3Gal as well as SA 2,6Gal capacity to hemagglutinate The HA of another egg-grown variant, although derivatized erythrocytes. structurally identical to HA of virus grown in MDCK cells, was nevertheless Therefore, the contribution of other influenza gene antigenically distinct. The products such as the matrix and neuraminidase is under investigation. isolation in eggs of antigenic and receptor-binding variants from a single highlights the need for care in the selection of the infected individual, most appropriate virus for epidemiological and vaccine purposes.
52
OF THE INTERFERON- AND VIRUS-INDUCIBLE
Hubert Hug, Luigi Bazzigher’, Weissmann.
llnstitut
lnstitut
fi.ir lmmunoiogie
The interferon that selectively
Maria Costas,
(IFN)-regulated
of influenza
over at least 55 kb of DNA.
non-coding
sequence
maximal
by IFN-a/8
virus.
is about
Zurich,
Zurich
of 14 exons,
and the first exon, comprising
of the promoter
140 bp upstream
is present in the Mx promoter
promoters
characterized
to date.
Newcastle
disease virus (NDV) as by IFN.
the Mx gene by virus is detectable
The Mx gene consists
to the IFN response.
PuGAAANt-2GA~PyPy
that this induction
CH-8093
CH-8028
a
by an intron of >30 kb from the second exon,
The 5’ boundary
At least two distinct regions contribute
possibility
Zgrich,
Zurich,
The Mx promoter
of 29 bp, are separated
the initiation codon.
induction
1, Un~versit~t
Universitat
and Charles
Mx gene of the mouse encodes the 72 kD nuclear Mx protein
inhibits the replication
distributed
which contains
Markus Aebi, Peter Staeheli*
fijr Moiekularbiologie und Virologie,
Mx PROMOTER
Surprisingly,
of the transcription A consensus
for
initiation
site.
sequence of the type
as well as in all other IFN-inducible
the Mx promoter
In cells with blocked
is induced
IFN.
other viruses besides NDV act as inducers of IFN-res~nsive
as efficiently
protein synthesis,
as early as 90 min after infection,
occurs via virus-induced
region required
virtually
excluding
We are now testing
by
induction
of
the
whether
genes.
98 ANTIe~IC ISOLATED
AND MOLECU~ FROM AN INFECTED
V~IATION INDIVIDUAL
IN SU~POPU~TIONS OF INFLUENZA IN DIFFERENT HOST CELLS
VIRUSES
JACQUELINE M. KATZ. MAOLIANG WANG, JAMES C PAULSON* AND ROBERT G. WEBSTER Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, 332 North Lauderdale, P.O. Box 318, Memphis, TN 38101 and *Department of Biological Chemistry, UCLA School of Medicine, Los Angeles, CA 90024. Influenza viruses grown in embryonated chicken eggs frequently possess antigenically and structurally distinguishable hemagglutinin (HA) compared to To investigate virus from the same source grown in mammalian cell culture. the extent of variation in the virus population which can be isolated from a single infected individual, viruses were isolated at limiting dilution from an original throat wash sample in eggs or mammalian MDCK cells, and the and receptor-binding properties of their HA molecules antigenic, structural The HA of virus clones isolated in MDCK cells were were determined. In contrast, viruses from the same antigenically and structurally identical. of three antigenic and structurally source isolated in eggs, consisted Amino acid substitutions in the HA of egg-grown distinct subpopulations. variants were clustered around the receptor-binding site of the molecule. One egg-grown variant population, possessing a single amino acid substitution altered receptor-binding properties as in antigenic site A, displayed to inhibition by non-immune horse serum and a indicated by resistance sialic acid (SA) 2,3Gal as well as SA 2,6Gal capacity to hemagglutinate The HA of another egg-grown variant, although derivatized erythrocytes. structurally identical to HA of virus grown in MDCK cells, was nevertheless Therefore, the contribution of other influenza gene antigenically distinct. The products such as the matrix and neuraminidase is under investigation. isolation in eggs of antigenic and receptor-binding variants from a single highlights the need for care in the selection of the infected individual, most appropriate virus for epidemiological and vaccine purposes.
52