Alteration of nuclear (2'-5')oligoriboadenylate synthetase and nuclease activities preceding replication of human immunodeficiency virus in H9 cells.
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.
Schröder
H C
HC
Institut für Physiologische Chemie, Universität Mainz.
Wenger
R
R
Rottmann
M
M
Müller
W E
WE
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology*; D002472:Cell Transformation, Viral; D004261:DNA Replication; D004722:Endoribonucleases / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D009685:Nuclear Envelope / Q000201:enzymology; D009693:Nucleic Acid Hybridization; D013379:Substrate Specificity; D014779:Virus Replication
D015088:2',5'-Oligoadenylate Synthetase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease