Induction of human immunodeficiency virus type 1 expression in chronically infected cells is associated primarily with a shift in RNA splicing patterns

We have analyzed the kinetics of human immunodeficiency virus type 1 (HIV-1) RNA induction in chronically infected T cells and promonocytes. A substantial amount of spliced mRNAs and assembled virions was found in resting cells. Induction increased the steady-state level of total HIV-1 RNA by 4-fold but increased the level of unspliced transcripts by 25-fold. This increase in unspliced RNA was reflected in the amount of virus seen by electron microscopy. These data suggest a mechanism for the induction of HIV-1 RNA in chronically infected cells involving a shift in splicing greatly favoring the stability of unspliced viral RNA with only a modest increase in total viral RNA. Analysis of the relative abundance of transcript classes is critical to the measurement of HIV-1 viral replication kinetics.

[1]  B. Cullen,et al.  Regulation of HIV‐1 gene expression , 1991, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[2]  D. Chang,et al.  Messenger RNA transport and HIV rev regulation. , 1990, Science.

[3]  M. Reitz,et al.  Structure and expression of tat-, rev-, and nef-specific transcripts of human immunodeficiency virus type 1 in infected lymphocytes and macrophages , 1990, Journal of virology.

[4]  A. Krainer,et al.  Purification and characterization of pre-mRNA splicing factor SF2 from HeLa cells. , 1990, Genes & development.

[5]  D. Baltimore,et al.  Lipopolysaccharide is a potent monocyte/macrophage-specific stimulator of human immunodeficiency virus type 1 expression , 1990, The Journal of experimental medicine.

[6]  D. Baltimore,et al.  Cells nonproductively infected with HIV-1 exhibit an aberrant pattern of viral RNA expression: A molecular model for latency , 1990, Cell.

[7]  P. Sharp,et al.  Regulation by HIV Rev depends upon recognition of splice sites , 1989, Cell.

[8]  I. Chen,et al.  Analysis of rev gene function on human immunodeficiency virus type 1 replication in lymphoid cells by using a quantitative polymerase chain reaction method , 1989, Journal of virology.

[9]  M. Mathews,et al.  HIV-1 Tat protein increases transcriptional initiation and stabilizes elongation , 1989, Cell.

[10]  F. Negro,et al.  Human herpes virus‐6 increases HIV‐1 expression in co‐infected T cells via nuclear factors binding to the HIV‐1 enhancer. , 1989, The EMBO journal.

[11]  D. Baltimore,et al.  Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: evidence for differential gene expression , 1989, Journal of virology.

[12]  B. Cullen,et al.  Regulatory pathways governing HIV-1 replication , 1989, Cell.

[13]  D. Baltimore,et al.  NF-κB: A pleiotropic mediator of inducible and tissue-specific gene control , 1989, Cell.

[14]  M. Emerman,et al.  The rev gene product of the human immunodeficiency virus affects envelope-specific RNA localization , 1989, Cell.

[15]  G. Nabel,et al.  Activation of HIV gene expression during monocyte differentiation by induction of NF-kB , 1989, Nature.

[16]  M. Hammarskjöld,et al.  Regulation of human immunodeficiency virus env expression by the rev gene product , 1989, Journal of virology.

[17]  P. Luciw,et al.  Structure, sequence, and position of the stem-loop in tar determine transcriptional elongation by tat through the HIV-1 long terminal repeat. , 1989, Genes & development.

[18]  J. Justement,et al.  Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[19]  S. Le,et al.  The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA , 1989, Nature.

[20]  T. Copeland,et al.  rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[21]  A. Fauci,et al.  Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone. , 1989, Journal of immunology.

[22]  J. Justement,et al.  Characterization of a promonocyte clone chronically infected with HIV and inducible by 13-phorbol-12-myristate acetate. , 1988, Journal of immunology.

[23]  M. Siekevitz,et al.  Activation of the HIV-1 LTR by T cell mitogens and the trans-activator protein of HTLV-I. , 1987, Science.

[24]  P. Luciw,et al.  Anti-termination of transcription within the long terminal repeat of HIV-1 by tat gene product , 1987, Nature.

[25]  R. Gaynor,et al.  Interactions of cellular proteins involved in the transcriptional regulation of the human immunodeficiency virus. , 1987, The EMBO journal.

[26]  P. Bingham,et al.  Developmental expression of a regulatory gene is programmed at the level of splicing. , 1987, The EMBO journal.

[27]  J. Kaufman,et al.  Phorbol ester enhances human immunodeficiency virus-promoted gene expression and acts on a repeated 10-base-pair functional enhancer element , 1987, Molecular and cellular biology.

[28]  B. Cullen,et al.  Trans-activation of human immunodeficiency virus gene expression is mediated by nuclear events. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[29]  M. Mckeown,et al.  Regulation of sexual differentiation in D. melanogaster via alternative splicing of RNA from the transformer gene , 1987, Cell.

[30]  G. Nabel,et al.  An inducible transcription factor activates expression of human immunodeficiency virus in T cells , 1987, Nature.

[31]  M. Feinberg,et al.  HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA , 1986, Cell.

[32]  R. Tjian,et al.  Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1. , 1986, Science.

[33]  S. Arya,et al.  Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). , 1985, Science.

[34]  J. Sodroski,et al.  Location of the trans-activating region on the genome of human T-cell lymphotropic virus type III. , 1985, Science.

[35]  M. Gonda,et al.  Sequence homology and morphologic similarity of HTLV-III and visna virus, a pathogenic lentivirus. , 1985, Science.

[36]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[37]  B. Nadal-Ginard,et al.  Alternative splicing: a ubiquitous mechanism for the generation of multiple protein isoforms from single genes. , 1987, Annual review of biochemistry.

[38]  S. Leff,et al.  Complex transcriptional units: diversity in gene expression by alternative RNA processing. , 1986, Annual review of biochemistry.