|
|
| TR |
TITLE |
AUTHORS |
KEYWORDS |
MATERIALS & METHODS
|
MICROSCOPIC
TECHNIQUES |
SPECIES |
MORPHOLOGY |
CELL
LINE |
| 601 |
HIV-1
Nef mediates post-translational down-regulation and
redistribution of the mannose receptor |
David
J. Vigerust, Brian S. Egan, and Virginia L. Shepherd |
macrophages,
trafficking, HIV-derived proteins |
Transfection of cells for confocal
experiments was performed in 35 mm glass-bottom dishes (MatTek, Ashland, MA). Briefly, 5 105
cells were seeded into each dish and incubated overnight.
|
Confocal
microscopy |
|
|
HeLa |
| Abstract |
| |
Human immunodeficiency virus (HIV) has derived a variety
of means to evade the host immune response. HIV-derived proteins, including Tat, Nef, and Env,
have all been reported to decrease expression of host molecules such as CD4 and major histocompatibility
complex I, which would assist in limiting viral replication. The mannose receptor (MR) on the
surface of macrophages and dendritic cells (DC) has been proposed to function as an effective
antigen-capture molecule, as well as a receptor for entering pathogens such as Mycobacterium
tuberculosis and Pneumocystis carinii. Regulation of this receptor would therefore benefit HIV
in removing an additional arm of the innate immune system. Previous work has shown that MR function
is reduced in alveolar macrophages from HIV-infected patients and that surface MR levels are
decreased by the HIV-derived protein Nef in DC. In addition, several laboratories have shown
that CD4 is removed from the surface of T cells in a manner that might be applicable to decreased
MR surface expression in macrophages. In the current study, we have investigated the role of
Nef in removing MR from the cell surface. We have used a human macrophage cell line stably expressing
the MR as well as human epithelial cells transiently expressing CD4 and a unique CD4/MR chimeric
molecule constructed from the extracellular and transmembrane domains of CD4 and the cytoplasmic
tail portion of the MR. We show that the MR is reduced on the cell surface by 50% in the presence
of Nef and that the MR cytoplasmic tail can confer susceptibility to Nef in the CD4/MR chimera.
These data suggest that the MR is a potential intracellular target of Nef and that this regulation
may represent a mechanism to further cripple the host innate immune system. |
|
|
|
|
