Increased poly(ADP-ribose)polymerase activity in cells infected by human immunodeficiency virus type-1

Microbiologica. 1991 Apr;14(2):141-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Survival
  • Cycloheximide / pharmacology
  • DNA Damage
  • Dactinomycin / pharmacology
  • HIV-1 / physiology*
  • Humans
  • Lymphocytes / enzymology
  • Lymphocytes / microbiology*
  • NAD / metabolism
  • Poly(ADP-ribose) Polymerases / blood
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Virus Replication

Substances

  • NAD
  • Dactinomycin
  • Cycloheximide
  • Poly(ADP-ribose) Polymerases