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Comprehensive analysis of LANA interacting proteins essential for viral genome tethering and persistence.
[primary effusion lymphoma]
Kaposi
's
sarcoma
associated
herpesvirus
is
tightly
linked
to
multiple
human
malignancies
including
Kaposi
's
sarcoma
(
KS
)
,
Primary
Effusion
Lymphoma
(
PEL
)
and
Multicentric
Castleman
's
Disease
(
MCD
)
.
KSHV
like
other
herpesviruses
establishes
life-
long
latency
in
the
infected
host
by
persisting
as
chromatin
and
tethering
to
host
chromatin
through
the
virally
encoded
protein
Latency
Associated
Nuclear
Antigen
(
LANA
)
.
LANA
,
a
multifunctional
protein
,
is
capable
of
binding
to
a
large
number
of
cellular
proteins
responsible
for
transcriptional
regulation
of
various
cellular
and
viral
pathways
involved
in
blocking
cell
death
and
promoting
cell
proliferation
.
This
leads
to
enhanced
cell
division
and
replication
of
the
viral
genome
,
which
segregates
faithfully
in
the
dividing
tumor
cells
.
The
mechanism
of
genome
segregation
is
well
known
and
the
binding
of
LANA
to
nucleosomal
proteins
,
throughout
the
cell
cycle
,
suggests
that
these
interactions
play
an
important
role
in
efficient
segregation
.
Various
biochemical
methods
have
identified
a
large
number
of
LANA
binding
proteins
,
including
histone
H
2
A
/
H
2
B
,
histone
H
1
,
MeCP
2
,
DEK
,
CENP-F
,
NuMA
,
Bub
1
,
HP
-
1
,
and
Brd
4
.
These
nucleosomal
proteins
may
have
various
functions
in
tethering
of
the
viral
genome
during
specific
phases
of
the
viral
life
cycle
.
Therefore
,
we
performed
a
comprehensive
analysis
of
their
interaction
with
LANA
using
a
number
of
different
assays
.
We
show
that
LANA
binds
to
core
nucleosomal
histones
and
also
associates
with
other
host
chromatin
proteins
including
histone
H
1
and
high
mobility
group
proteins
(
HMGs
)
.
We
used
various
biochemical
assays
including
co
-immunoprecipitation
and
in
-vivo
localization
by
split
GFP
and
fluorescence
resonance
energy
transfer
(
FRET
)
to
demonstrate
their
association
.
Diseases
Validation
Diseases presenting
"virally encoded protein"
symptom
primary effusion lymphoma
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