The cytopathic effect of human immunodeficiency virus is independent of high levels of unintegrated viral DNA accumulated in response to superinfection of cells.

Abstract

Large quantities of genome-sized viral DNA are detected in the nucleoplasm of CD4+ T cells infected with human immunodeficiency virus type 1 (HIV-1). This unintegrated HIV DNA is in the form of both circular and linear species. Accumulation of such DNA occurs gradually during a 5 day HIV infection and is correlated with the proportion of cells involved in the production of HIV proteins. To pinpoint the stage in a synchronized HIV infection during which accumulation of HIV DNA occurs, high titres of HIV were employed to infect CEM cells to infect the majority of cells by the input virus. By this latter infection, more than 95% of cells became producers of HIV proteins at 48 h post-infection (p.i.) concomitantly with the development of the c.p.e. of HIV, manifested by formation of syncytia and induction of cell death by apoptosis. Addition of azidothymidine (AZT) or neutralizing anti-gp120 monoclonal antibodies at 8 h p.i. did not alter the course of virus infection nor the amount of virus produced at 48 h p.i. but the accumulation of unintegrated HIV DNA was drastically reduced. These results indicate that viral DNA accumulates as a result of superinfection of cells late in the virus cycle. The development of the c.p.e. of HIV was inhibited in the presence of neutralizing antibodies, whereas in the presence of AZT the accumulation of unintegrated HIV DNA was completely blocked without apparent effect on the c.p.e. These observations indicate that the c.p.e. of the HIV infection, which is manifested by syncytium formation and apoptosis, does not require superinfection of cells or accumulation of unintegrated viral DNA.