2026-09-24T18:10:13Zhttps://iris.unica.it/oai/requestoai:iris.unica.it:11584/2668972022-10-20T09:35:18Zcom_11584_207615com_11584_111066col_11584_265854
Characterization of the human endogenous retrovirus
HERV-‐K(HML-‐6) and HERV-‐K(HML-‐10) sequences and
analysis of their expression
CADEDDU, MARTA
HERVS
HML-10
HML-6
autoimmune diseases
retrovirus endogeni
Settore BIO/19 - Microbiologia Generale
It has been estimated
that
8%
of
human
genome
is
composed
of
sequences
originating
from
exogenous
retroviruses
that
infected
the
germ
line
cells
over
millions
of
years
and
are
termed
human
endogenous
retroviruses
(HERVs).
After
germ
line
infection,
the
retroviral
DNA
was
integrated
into
the
genome
and
transmitted
through
vertical
transmission
in
the
progeny
by
Mendelian
laws.
ERVs
have
been
found
in
all
vertebrates,
indicating
that
the
process
of
endogenization
was
quiet
common,
and
have
been
considered
retroviral
fossil
whose
phylogenetic
analysis
provides
important
information
on
evolution.
During
the
million
of
years
after
their
integration,
ERV
sequences
have
accumulated
abundant
mutations
(deletions,
insertions,
duplications,
and
rearrangements)
that
have
caused
loss
of
virulence,
contributing
to
the
current
composition
of
the
actual
HERV.
Several
studies
suggested
the
ability
of
HERVs
to
significantly
interfere
in
human
biology,
in
both
physiological
and
pathological
scenarios.
However,
despite
a
few
cases
such
as
the
one
of
Syncityn--‐1,
the
HERV
physiological
role
an
their
involvement
in
the
development
of
diseases
such
as
cancer,
autoimmune
diseases,
neuronal
diseases
and
other
disorders
is
still
controversial.
Among
the
most
studied
HERVs
is
the
betaretrovirus
HERV--‐K(HML1--‐10)
clade,
composed
of
10
groups
whose
correlation
with
diseases
has
been
proposed
in
a
number
of
cases.
In
particular,
it
has
been
reported
that
the
env
gene,
termed
HERV--‐K--‐MEL,
is
expressed
in
melanoma
cells
and
not
in
healthy
controls.
In
addition,
it
has
been
demonstrated
that
the
low
copy
number
of
HML--‐10
sequences
within
the
complement
C4
gene
of
the
major
histocompatibility
complex
is
related
to
a
higher
frequency
of
Type
1
Diabetes,
hypothesizing
that
these
elements
could
act
as
antisense
control
or
be
controlled
by
other
HML--‐10
sequences
that
could
be
involved
in
Type
1
Diabetes.
Given
the
many
accumulated
mutations
and
their
high
copy
number,
HERV
studies
have
been
hampered
by
the
lack
of
precise
information
on
their
chromosomal
localization
and
composition.
Recently,
the
use
of
a
novel
bionfomatic
approach
allowed
us
to
precise
identify
a
total
of
3173
sequences
in
5
the
human
genome
assembly
GRCh37/hg19.
Hence
in
the
present
work
we
wanted
to
fully
characterize
two
HERV--‐K
subgroups,
the
HML--‐10
subgroup
that
includes
9
proviruses
with
5
haplotypes,
and
the
HML--‐6
subgroup
that
includes
63
proviruses.
The
HML--‐10
and
HML--‐6
analysis
allowed
to
i)
confirming
their
classification
by
an
innovative
methodology
of
Similarity
image
(Simage)
analysis,
ii)
precisely
defining
the
retroviral
structure
in
each
locus,
iii)
determining
the
presence
of
the
betaretrovirus
feature
in
all
the
identified
sequences;
iv)
assessing
the
putative
time
of
integration
of
each
retroviral
sequence
and
v)
verifying
the
presence
of
some
of
the
sequences
also
in
no--‐
human
primates.
In
addition,
we
assessed
the
expression
of
HML--‐10
and
HML--‐6
sequences
by
analyzing
three
public
RNAseq
databases
comprising
>
30
different
tissues
isolated
from
healthy
individuals
as
well
as
mRNA
from
patients
with
autoimmune
diseases
such
as
Type
1
Diabetes,
Systemic
Lupus
Erythematosus
and
Multiple
Sclerosis.
Data
showed
that
some
HML--‐6
sequences
are
expressed
in
a
number
of
healthy
tissues
while
no
HML--‐10
expression
has
been
specifically
observed
in
these
dataset.
Overall,
these
results
increase
the
knowledge
of
the
composition
of
the
human
genome
and
lay
the
foundation
for
a
better
understanding
of
the
potential
physiological
and
pathological
role
of
HML--‐6
and
HML--‐10
retroviruses.
2016-03-11
info:eu-repo/semantics/doctoralThesis
http://hdl.handle.net/11584/266897
eng
numberofpages:97
info:eu-repo/semantics/openAccess
Università degli Studi di Cagliari
license:Non specificato