Document 0094
 DOCN  M9460094
 TI    Human immunodeficiency virus type 1 RNA expression by four chronically
       infected cell lines indicates multiple mechanisms of latency.
 DT    9404
 AU    Butera ST; Roberts BD; Lam L; Hodge T; Folks TM; Retrovirus Diseases
       Branch, Centers for Disease Control and; Prevention, Atlanta, Georgia
       30333.
 SO    J Virol. 1994 Apr;68(4):2726-30. Unique Identifier : AIDSLINE
       MED/94187114
 AB    Recent information has suggested that posttranscriptional mechanisms,
       whereby human immunodeficiency virus type 1 (HIV-1) RNA exists as
       multiply spliced transcripts without promoting an accumulation of the
       larger messages, are responsible for maintaining a stable state of
       nonproductive viral expression or viral latency. To test the
       universality of these observations, we compared the patterns of viral
       RNA splicing and the frequencies of cells actually harboring HIV-1 RNA
       in four chronically HIV-1-infected cell lines (U1 [promonocytic], ACH-2
       [T lymphocytic], OM-10.1 [promyelocytic], and J1.1 [T lymphocytic]). In
       uninduced U1 and ACH-2 cultures, a high frequency of cells
       (approximately one in six) contained HIV-1 RNA but mainly as multiply
       spliced transcripts, again supporting a posttranscriptional mechanism
       maintaining viral latency. In sharp contrast, only 1 in 50 cells in
       uninduced OM-10.1 and J1.1 cultures contained HIV-1 RNA, indicating a
       primary transcriptional mechanism controlling viral expression in these
       cells. Furthermore, those OM-10.1 and J1.1 cells that did contain viral
       RNA were in a state of productive HIV-1 expression marked by the
       presence of both spliced and unspliced transcripts. Even though the
       total absence of viral RNA in the majority of OM-10.1 and J1.1 cells
       indicated a state of absolute latency, treatment with tumor necrosis
       factor alpha induced transcription of HIV-1 RNA in nearly 100% of the
       cells in all four of the chronically infected cultures. Tumor necrosis
       factor alpha induction of U1, ACH-2, and OM-10.1 cultures resulted in an
       initial accumulation of multiply spliced HIV-1 RNA followed by a
       transition to the larger unspliced viral RNA transcripts. This RNA
       splice transition was less apparent in the J1.1 cell line. These results
       demonstrate that host cell-specific transcriptional and
       posttranscriptional mechanisms are important factors in the control of
       HIV-1 latency.
 DE    Cell Line  Comparative Study  Hematopoietic Stem Cells/MICROBIOLOGY
       Human  HIV-1/GROWTH & DEVELOPMENT/*GENETICS  Monocytes/MICROBIOLOGY
       Polymerase Chain Reaction  Reverse Transcriptase/GENETICS  *RNA Splicing
       RNA, Messenger/*BIOSYNTHESIS  RNA, Viral/*BIOSYNTHESIS
       T-Lymphocytes/MICROBIOLOGY  Virus Latency/*GENETICS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).