Negative regulation of human immune deficiency virus replication in monocytes. Distinctions between restricted and latent expression in THP-1 cells

Abstract

In THP-1 monocytoid cells infected with HIV, viral expression can be regulated in several ways: (a) latency (no viral expression); (b) restricted expression (chronic low-level viral expression with little or no detectable virus released); and (c) continuous production. In cells with restricted HIV expression, nuclear factor(s) were found that blocked tat-associated DNA binding complex formation, suggesting that initiation of transcription was negatively regulated. Also, viral particles were seen budding into and accumulating within intracytoplasmic vacuoles with little virus released, suggesting multiple levels of regulation. These cells with restricted expression had no detectable viral antigens on the cell surface and were not lysed by IL-2-activated large granular lymphocytes. However, they could cause viral-mediated T cell cytolysis in cell-cell assays, suggesting viral transmission through cell contact. In addition, cells with latent HIV were identified and could still produce infectious virus after 5-azacytidine exposure 10 mo later. LPS and other treatments could increase viral production in cells with restricted but not latent expression, suggesting they occur by distinct mechanisms. These infected cells provide a reservoir for viral transmission to uninfected T cells that itself is not detected by immune surveillance mechanisms.