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@PHDTHESIS{Mtter:837194,
author = {Mötter, Jessica},
title = {{I}dentifizierung von {I}nteraktionspartnern für {HIV}-1
{N}ef und ihre potentielle {R}elevanz bei der {E}ntwicklung
der {HIV}-assoziierten {D}emenz},
volume = {19},
school = {Universität Düsseldorf},
type = {Dr.},
address = {Jülich},
publisher = {Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag},
reportid = {FZJ-2017-06173},
isbn = {978-3-89336-604-0},
series = {Schriften des Forschungszentrums Jülich. Reihe Gesundheit
/ Health},
pages = {VI, 173 S : Ill., graph. Darst},
year = {2010},
note = {Keine Online-Freischaltung; Universität Düsseldorf,
Diss., 2010},
abstract = {Neuro-Aids as a consequence of infection with human
immundeficiency virus (HIV), becomes increasingly important
due to considerably more efficient anti-AIDS therapies that
result in longer life expectancy. Besides HIV Tat the viral
Nef protein is hypothesized to play a role in development of
Neuro-AIDS. Till today the detailed function of HIV-1 Nef
protein in the development of neurological manifestations of
an HIV infection is not known. Possibly, Nef could
contribute to open the blood-brain barrier by activating
matrix metalloproteinase-9 allowing HIV to enter the central
nervous system. Furthermore, Nef is known to induce
chemokine CCL2/MCP1 expression, which causes infiltration of
the brain by monocytes. It is also known that
oligodendrocytes initiate vacuolar myelopathy. This is
amongst others a disease pattern of HIV associated
neuromanifestations. Thus, for elucidation of HIV associated
neuromanifestations on the molecular level Nef is an
interesting candidate. Aim of the present work was the
identification of new cellular interaction partners for
HIV-1 Nef protein with a potential role in development of
HIV associated dementia (HAD). Knowledge of new brain
specific interaction partners of Nef may lead to a better
understanding of Nef cellular functions. Use of a modern
yeast two-hybrid system yielded succeessful identification
of proteins as so far unknown interaction partners of
membrane associated Nef. A total of 21 proteins, including
17 membrane proteins, were verified as interaction partners
of Nef in the yeast system. Some of them may be relevant for
HIV/HAD. B-cell receptor-associated protein 31 (Bcap31) was
the second most prevalent hit. The interaction of Nef with
Bcap31 could be confirmed with coimmunprecipitation in yeast
cells. Furthermore, colocalization in Neuro2A cells in
structures at plasma membrane succeeded. The glycoprotein
M6B (GPM6B) was the most dominant hit in the screen and its
interaction with Nef was characterized in detail in the
present work. The interaction of Nef with GPM6B could be
verified by coimmunprecipitation from yeast cell extract and
pulldown assays using rat brain. Furthermore, Nef and GPM6B
colocalized in Neuro2A cells and the relevant binding region
in GPM6B could be defined to a 16 amino acid residue region,
which is very similar to the Nef-binding region of human
CD4. Fluorescence measurements resulted in a submicromolar
dissociation constant for this interaction. The results
obtained in the present work deliver important contributions
for a deeper understanding of Nef’s function in HAD.},
keywords = {HIV (gnd) / Gen nef (gnd) / Demenz (gnd)},
cin = {ISB-3},
ddc = {610},
cid = {I:(DE-Juel1)VDB942},
pnm = {899 - ohne Topic (POF3-899)},
pid = {G:(DE-HGF)POF3-899},
typ = {PUB:(DE-HGF)3 / PUB:(DE-HGF)11},
url = {https://juser.fz-juelich.de/record/837194},
}