Accumulation of transcripts coding for prion protein in human astrocytes during infection with human immunodeficiency virus.
The abnormal isoforms of the normal cellular prion protein (PrP), also termed Scrapie-associated fibril protein, are assumed to be one causative factor of spongiform encephalopathies. The mRNA of PrP contains stem-loop structures which are very similar to the human immunodeficiency virus-1 (HIV-1) cis-acting sequence TAR within the LTR; both structures contain the pentanucleotide CUGGG in the loop, and the uridine- and adenine-bulge in the stem. In this study, using purified HIV-encoded trans-activator, Tat, and HIV-1 TAR-RNA or PrP-mRNA containing the stem-loop structure, we demonstrate by use of gel-retardation and filter binding assays that Tat binds to TAR- and PrP-RNA with the dissociation constants of 2.9 or 37.0 nM, respectively, at a molar ratio of 0.7 mol of Tat to 1 mol of RNA fragment. The Tat-RNA (TAR or PrP) complexes bind to protein(s) in the nuclear matrix, isolated from human astrocytes (glial fibrillary acidic protein positive brain cells). Infection of astrocytes with HIV-1 resulted in an increased level of PrP mRNA. The data presented led us to assume that certain sequences in the PrP mRNA might be targets for proteins acting in trans.
Institut für Physiologische Chemie, Universität Mainz, Germany.
W E
WE
Müller
K
K
Pfeifer
J
J
Forrest
P G
PG
Rytik
V F
VF
Eremin
S A
SA
Popov
H C
HC
Schröder
D001253:Astrocytes / Q000378:metabolism* / Q000382:microbiology; D001483:Base Sequence; D001667:Binding, Competitive; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D015696:Gene Products, tat / Q000378:metabolism / Q000502:physiology; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D018620:PrPSc Proteins; D011328:Prions / Q000235:genetics* / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D014158:Transcription, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D018620:PrPSc Proteins; D011328:Prions; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus