High levels of 2',5'-oligoadenylate synthetase and 2',5'-oligoadenylate-dependent endonuclease in human trophoblast.
Human placenta contains a high level of 2',5'-oligoadenylate (2-5A) synthetase activity of the 100-kD form of the enzyme. About 20% of the placental 2-5A synthetase activity was found to be cytosolic, whereas the remaining 80% was released by 0.5 M KCl in the presence of detergent. Most of the enzyme activity was localized in trophoblast cells, which also contain a high level of 2-5A-dependent RNase L activity. The purified trophoblast 100-kD 2-5A synthetase was shown to be activated by human immunodeficiency virus type 1 (HIV-1) 5' RNA 1-311 and 1-707, which both contain the TAR and primer binding site (PBS) structured regions. These two HIV-1 RNAs activated human trophoblast 2-5A synthetase at the same level as poly(I).poly (C), a standard highly efficient activator of the enzyme, and at the same optimal concentration. On the contrary, HIV-1 RNA 311-618, a poorly structured region missing TAR and PBS, was shown to be a poor activator of the enzyme. The specific cellular location of the 2-5A synthetase and its efficient activation by HIV 5' RNA favors the idea that the trophoblast 2-5A system negatively controls HIV replication in trophoblasts.
Zhang
G Y
GY
INSERM U. 245, Paris, France.
Beltchev
B
B
Fournier
A
A
Zhang
Y H
YH
Malassiné
A
A
Bisbal
C
C
Ehresmann
B
B
Ehresmann
C
C
Darlix
J L
JL
Thang
M N
MN
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism*; D004722:Endoribonucleases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000635:transmission; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D012367:RNA, Viral / Q000494:pharmacology; D014327:Trophoblasts / Q000201:enzymology* / Q000382:microbiology*; D014779:Virus Replication
D012367:RNA, Viral; D015088:2',5'-Oligoadenylate Synthetase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease