Genetic changes associated with distinct patterns of HIV type 1 persistence in chronically infected cell lines

Three persistently infected cell lines (H61, M61, and U61) were established by infection with an HIV-1 isolate (s61) of two T cell lines, H9 and MT-4, and the promonocytic U937-2. In H61, 35% of cells expressed viral antigens yielding low virus titers and a majority of mature particles. M61 showed viral expression in every cell but with the frequent generation of immature particles. In U61, 1% of cells displayed viral expression, which increased after cell activation, indicating a latent infection. Nucleotide sequences of the complete provirus from the persistent cell lines revealed extremely high mutation rates in accessory genes and non-coding regions from 1.1 to 2.8 x 10(-2), whereas in structural genes they ranged from 3.2 to 9.8 x 10(-3). Ten nonsynonymous mutations were shared by all persistent proviruses including five strong amino acid changes in the env gene (related to the NSI phenotype) and in vpr and tat genes; other alterations were in accessory genes and two in the USF and c-Myb motifs in LTR. Truncated vpr and vpu proteins were found specifically in H61 and in vif in M61. This comprehensive study disclosed the role of the cell on the HIV-1 persistence pattern as well as common and specific mutations in the virus.