Alteration of nuclear (2'-5')oligoriboadenylate synthetase and nuclease activities preceding replication of human immunodeficiency virus in H9 cells.

Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.

Alteration of nuclear (2'-5')oligoriboadenylate synthetase and nuclease activities preceding replication of human immunodeficiency virus in H9 cells.

Biol Chem Hoppe Seyler. 1988 Sep;369(9):985-95. Unique Identifier : AIDSLINE MED/89149964
Schroder HC; Wenger R; Rottmann M; Muller WE; Institut fur Physiologische Chemie, Universitat Mainz.

Abstract: After infection of the respective target cells with the human immunodeficiency virus (HIV-1) viral progeny is produced only after a short temporary delay of some days, depending on cell type. After this period of time a sudden onset of HIV-1 protein synthesis with a dramatic increase in virus release occurs. (2'-5')Oligoriboadenylates [(2'-5')A], capable to activate a latent ribonuclease (RNase L) degrading both mRNA and rRNA, are known mediators involved in the early response of cells to virus infection. Here we show that the (2'-5')A-synthesizing (2'-5')A synthetase, which is inducible by interferon and activated by double-stranded RNA, as well as a (2'-5')A nuclease (2',3'-exoribonuclease) are associated with the nuclear matrix of uninfected and infected H9 cells, also in the absence of interferon. Infection of H9 cells with HIV-1 was found to cause a strong (7.7-fold) enhancement of (2'-5')A synthetase activity and a smaller (2-fold) increase of 2',3'-exoribonuclease activity. Simultaneously the concentration of synthesized (2'-5')A increased 5 to 10 times in isolated nuclei. After incubation for 2 to 3 days both enzyme activities reached a maximum and then dropped below their initial values. Concomitantly a drastic increase in virus production occurred, as judged by reverse transcriptase activity in the culture fluid. These results suggest that the (nuclear matrix-associated) (2'-5')A system might be important during the initial stage of HIV infection, also by destructing matrix-bound viral messengers.

Keywords: Cell Line Cell Nucleus/*ENZYMOLOGY *Cell Transformation, Viral *DNA Replication Endoribonucleases/*METABOLISM Human HIV-1/*GENETICS Kinetics Nuclear Membrane/ENZYMOLOGY Nucleic Acid Hybridization Substrate Specificity Support, Non-U.S. Gov't Virus Replication 2',5'-Oligoadenylate Synthetase/*METABOLISM JOURNAL ARTICLE

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