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

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.