Extrachromosomal human immunodeficiency virus type 1 sequences are methylated in latently infected U937 cells

Virology. 1992 Jun;188(2):451-8. doi: 10.1016/0042-6822(92)90498-e.


Long-term human immunodeficiency virus type 1 (HIV-1) infection of the human monocytic cell line U937 resulted in a progressive loss of infectivity that was correlated with the accumulation of stable, extrachromosomal forms of viral DNA. Viral latency was also characterized by reduced levels of HIV-1 transcription. The structure and activity of extrachromosomal viral DNA (E-DNA) in a fully latent U937 cell line was investigated by molecular cloning and DNA transfection. The resulting 18-kb E-DNA clone was composed of an intact HIV-1 sequence flanked by 7 kb of host sequence to one side and 1 kb of host DNA to the other side. This configuration is the result of retroviral integration into a highly repetitive element of the Alu family. Transfection of the E-DNA clone resulted in the production of infectious virus, indicating that viral latency was not the result of mutations in the HIV-1 genome. Analysis of CCGG sites revealed extensive de novo methylation of viral sequences present within E-DNA. These results suggest that modification of extrachromosomal viral DNA sequences is a mechanism for HIV-1 latency in long-term infected U937 cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cloning, Molecular
  • DNA, Viral / genetics*
  • Extrachromosomal Inheritance
  • Gene Expression Regulation, Viral
  • HIV Long Terminal Repeat
  • HIV-1 / genetics*
  • Humans
  • In Vitro Techniques
  • Methylation
  • Molecular Sequence Data
  • Monocytes / microbiology*
  • Restriction Mapping
  • Tumor Cells, Cultured
  • Virus Replication*


  • DNA, Viral