Restricted expression of HIV1 in human astrocytes: molecular basis for viral persistence in the CNS.
Besides macrophages and microglial cells, cells of astroglial origin are thought to be targets of HIV1 in the brain. HIV1 infection of astroglial cells results in restricted production of the virus. To analyse the molecular basis of this restricted infection phenotype, we established a chronically HIV1-infected low-producer astrocytoma cell line. These cells show only low levels of mRNA encoding structural proteins, due to a cell-determined blockage in the Rev/RRE regulatory axis. The low-producer state could not be overcome by treatment with known stimulators of virus expression such as phorbol ester, (12-O-tetradecanoylphorbol-13-acetate), tumour necrosis factor alpha or sodium butyrate. This indicates that the molecular mechanisms involved in restricting virus production in astroglial cells differ from those in latently infected T cells and monocytes.
Kleinschmidt
A
A
GSF-Institute of Molecular Virology, Oberschleissheim, Germany.
Neumann
M
M
Möller
C
C
Erfle
V
V
Brack-Werner
R
R
D001253:Astrocytes / Q000821:virology*; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002460:Cell Line; D002490:Central Nervous System / Q000821:virology; D015870:Gene Expression / Q000187:drug effects; D015693:Gene Products, nef / Q000096:biosynthesis; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus
D002087:Butyrates; D015693:Gene Products, nef; D016655:HIV Core Protein p24; D012333:RNA, Messenger; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D054311:nef Gene Products, Human Immunodeficiency Virus; D020148:Butyric Acid; D013755:Tetradecanoylphorbol Acetate