Cell Host & Microbe,
Journal Year:
2018,
Volume and Issue:
24(3), P. 447 - 460.e11
Published: Aug. 16, 2018
Human
cytomegalovirus
(HCMV)
is
an
important
pathogen
with
multiple
immune
evasion
strategies,
including
virally
facilitated
degradation
of
host
antiviral
restriction
factors.
Here,
we
describe
a
multiplexed
approach
to
discover
proteins
innate
function
on
the
basis
active
by
proteasome
or
lysosome
during
early-phase
HCMV
infection.
Using
three
orthogonal
proteomic/transcriptomic
screens
quantify
protein
degradation,
high
confidence
identified
35
enriched
in
A
final
screen
employed
comprehensive
panel
viral
mutants
predict
genes
that
target
>250
human
proteins.
This
revealed
helicase-like
transcription
factor
(HLTF),
DNA
helicase
repair,
potently
inhibits
early
gene
expression
but
rapidly
degraded
The
functionally
unknown
UL145
facilitates
HLTF
recruiting
Cullin4
E3
ligase
complex.
Our
and
data
will
enable
further
identifications
pathways
targeted
other
viruses.
Nature Communications,
Journal Year:
2018,
Volume and Issue:
9(1)
Published: May 11, 2018
The
type
I
interferon
(IFN)
system
plays
an
important
role
in
controlling
herpesvirus
infections,
but
it
is
unclear
which
IFN-mediated
effectors
interfere
with
replication.
Here
we
report
that
human
myxovirus
resistance
protein
B
(MxB,
also
designated
Mx2)
a
potent
restriction
factor
the
context
of
IFN.
We
demonstrate
ectopic
MxB
expression
restricts
range
herpesviruses
from
Alphaherpesvirinae
and
Gammaherpesvirinae,
including
herpes
simplex
virus
1
2
(HSV-1
HSV-2),
Kaposi's
sarcoma-associated
(KSHV).
HSV-1
HSV-2
requires
GTPase
function,
contrast
to
lentiviruses.
inhibits
delivery
incoming
DNA
nucleus
appearance
empty
capsids,
not
capsid
cytoplasm
or
tegument
dissociation
capsid.
Our
study
identifies
as
pan-herpesvirus
blocks
uncoating
viral
The Journal of Experimental Medicine,
Journal Year:
2018,
Volume and Issue:
215(9), P. 2289 - 2310
Published: Aug. 1, 2018
Patients
with
epidermodysplasia
verruciformis
(EV)
and
biallelic
null
mutations
of
TMC6
(encoding
EVER1)
or
TMC8
(EVER2)
are
selectively
prone
to
disseminated
skin
lesions
due
keratinocyte-tropic
human
β-papillomaviruses
(β-HPVs),
which
lack
E5
E8.
We
describe
EV
patients
homozygous
for
the
CIB1
gene
encoding
calcium-
integrin-binding
protein-1
(CIB1).
is
strongly
expressed
in
cultured
keratinocytes
controls
but
not
those
patients.
forms
a
complex
EVER1
EVER2,
proteins
EVER1-
EVER2-deficient
cells.
The
known
functions
EVER2
dependent
on
CIB1,
deficiency
does
impair
keratinocyte
adhesion
migration.
In
keratinocytes,
protein
interacts
HPV
E8
encoded
by
α-HPV16
γ-HPV4,
respectively,
suggesting
that
this
acts
as
restriction
factor
against
HPVs.
Collectively,
these
findings
suggest
disruption
CIB1–EVER1–EVER2-dependent
keratinocyte-intrinsic
immunity
underlies
selective
susceptibility
β-HPVs
Cell Host & Microbe,
Journal Year:
2018,
Volume and Issue:
24(3), P. 447 - 460.e11
Published: Aug. 16, 2018
Human
cytomegalovirus
(HCMV)
is
an
important
pathogen
with
multiple
immune
evasion
strategies,
including
virally
facilitated
degradation
of
host
antiviral
restriction
factors.
Here,
we
describe
a
multiplexed
approach
to
discover
proteins
innate
function
on
the
basis
active
by
proteasome
or
lysosome
during
early-phase
HCMV
infection.
Using
three
orthogonal
proteomic/transcriptomic
screens
quantify
protein
degradation,
high
confidence
identified
35
enriched
in
A
final
screen
employed
comprehensive
panel
viral
mutants
predict
genes
that
target
>250
human
proteins.
This
revealed
helicase-like
transcription
factor
(HLTF),
DNA
helicase
repair,
potently
inhibits
early
gene
expression
but
rapidly
degraded
The
functionally
unknown
UL145
facilitates
HLTF
recruiting
Cullin4
E3
ligase
complex.
Our
and
data
will
enable
further
identifications
pathways
targeted
other
viruses.
