Increased poly(ADP-ribose)polymerase activity in cells infected by human immunodeficiency virus type-1.
Poly(ADP-ribose)polymerase is a chromatin-bound enzyme which is activated by free DNA ends and is therefore stimulated by a variety of DNA-damaging agents. The enzyme transfers the ADP moiety of NAD to nuclear proteins to create protein-bound ADP-ribose polymers. Under conditions favouring an accelerated poly(ADP-ribose) polymer formation, the enzyme may exhaust cellular NAD pools. At the same time, or shortly thereafter ATP levels drop and cell viability eventually declines. As a series of chemical and physical agents which may play a role in activating latent HIV-1 infection or favouring HIV-1 replication, have a DNA-damaging activity, we investigated the behaviour of poly(ADP-ribose)polymerase activity in various types of HIV-1-infected cells. The results obtained show that HIV-1-infected cells to possess an increased poly(ADP-ribosol)ating activity together with an accentuated fragmentation of cellular DNA which are associated with the time course of HIV-1 replication. These data give circumstantial support to the hypothesis that a NAD-depdendent cellular suicide response to DNA damage, could play a role in the death of HIV-1 infected cells. In this respect, the impared immunocompetence of HIV-1-infected patients could bear some resemblance to immune attribution that sometimes accompanies some inborn errors affecting DNA precursor metabolism and DNA integrity.
Furlini
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Institute of Microbiology, University of Bologna, Medical School, S. Orsola Hospital, Bologna, Italy.
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La Placa
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D002460:Cell Line; D002470:Cell Survival; D003513:Cycloheximide / Q000494:pharmacology; D004249:DNA Damage; D003609:Dactinomycin / Q000494:pharmacology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology / Q000382:microbiology*; D009243:NAD / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000097:blood / Q000378:metabolism*; D014779:Virus Replication
D009243:NAD; D003609:Dactinomycin; D003513:Cycloheximide; D011065:Poly(ADP-ribose) Polymerases