HIV-1 extrachromosomal 2-LTR circular DNA is long-lived in human macrophages

Abstract

HIV-1 extrachromosomal 2-LTR circles (cc2LTR) are rapidly lost in dividing cell populations and, therefore, might be interpreted as representing new infection and ongoing viral replication. However, recent work demonstrated that cc2LTR persist in infected, growth-arrested T cell lines beyond their predicted half-life as previously determined in dividing cell populations. In this study, the evaluation of the stability of cc2LTR was extended to include primary human macrophages, a natural, non-dividing target of HIV-1. By quantitative real-time PCR, cc2LTR were found to persist out to 21 days post-infection in macrophages infected with both integrase competent and integrase- defective, recombinant HIV-1, whereas in activated CD4(+) T lymphocytes, they rapidly decreased over time. This persistence was associated with persistent, low level expression of the indicator gene, luciferase. These data suggest that the presence of HIV-1 cc2LTR in the PBMC of HIV-1-infected patients on suppressive HAART could be due either to ongoing generation of newly infected dividing cells, or persistence of circles in non-dividing cell populations where they appear to be stable. Furthermore, exrachromosomal circular DNA in this cell population could be a source of persisent viral protein expression.