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

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.

• Authors: H C Schröder, R Wenger, M Rottmann, W E Müller
• Journal: Biological chemistry Hoppe-Seyler (Biol Chem Hoppe Seyler) Vol. 369 Issue 9 Pg. 985-95 (Sep 1988) ISSN: 0177-3593 [Print] Germany
• PMID: 3228494 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2',5'-Oligoadenylate Synthetase
• Endoribonucleases
• 2-5A-dependent ribonuclease

Topics

• 2',5'-Oligoadenylate Synthetase (metabolism)
• Cell Line
• Cell Nucleus (enzymology)
• Cell Transformation, Viral
• DNA Replication
• Endoribonucleases (metabolism)
• HIV-1 (genetics)
• Humans
• Kinetics
• Nuclear Envelope (enzymology)
• Nucleic Acid Hybridization
• Substrate Specificity
• Virus Replication