Control of human immunodeficiency virus replication by the tat, rev, nef and protease genes.

Immediately after infection, human immunodeficiency virus directs the synthesis of three regulatory proteins tat, rev and nef that together allow the synthesis of the structural proteins of the virus after a delay of several hours. Viral mRNA production is controlled by the tat gene, which appears to stimulate elongation by RNA polymerase II, and the rev gene, which allows the accumulation of unspliced or partially spliced mRNAs in the cytoplasm. The nef gene is dispensible for virus growth but may limit virus spread by downregulating the levels of cellular surface proteins such as the CD4 receptor. Virus maturation also depends critically on the protease gene which allows the orderly rearrangement of the viral core structures in newly budded virions as well as the vpu and vif genes which allow efficient production of mature envelope glycoprotein.

[1]  K. Cook,et al.  Specific binding of HIV-1 recombinant Rev protein to the Rev-responsive element in vitro , 1989, Nature.

[2]  H. Kräusslich Human immunodeficiency virus proteinase dimer as component of the viral polyprotein prevents particle assembly and viral infectivity. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[3]  T. Klimkait,et al.  The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release , 1990, Journal of virology.

[4]  L. Ratner,et al.  Human immunodeficiency virus type 1 negative factor is a transcriptional silencer. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J. Sodroski,et al.  A second post-transcriptional trans-activator gene required for HTLV-III replication , 1986, Nature.

[6]  A. Chambers,et al.  A nuclear translational block imposed by the HIV-1 U3 region is relieved by the Tat-TAR interaction , 1990, Cell.

[7]  B. Peterlin,et al.  Human immunodeficiency virus type 1 Tat does not transactivate mature trans-acting responsive region RNA species in the nucleus or cytoplasm of primate cells , 1991, Journal of virology.

[8]  J. Zack,et al.  Characterization and expression of novel singly spliced RNA species of human immunodeficiency virus type 1 , 1990, Journal of virology.

[9]  D. Baltimore,et al.  A human cell factor is essential for HIV‐1 Rev action. , 1990, The EMBO journal.

[10]  N. Sarver,et al.  Genetic characterization of human immunodeficiency virus type 1 nef gene products translated in vitro and expressed in mammalian cells , 1991, Journal of virology.

[11]  Brian W. Metcalf,et al.  Inhibition of HIV-1 protease in infected T-lymphocytes by synthetic peptide analogues , 1990, Nature.

[12]  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.

[13]  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.

[14]  Michael R. Green,et al.  Activation of transcription by HIV-1 Tat protein tethered to nascent RNA through another protein , 1990, Nature.

[15]  Michael R. Green,et al.  Sequence-specific RNA binding by the HIV-1 Rev protein , 1989, Nature.

[16]  Bryan R. Cullen,et al.  HIV-1 structural gene expression requires binding of the rev trans-activator to its RNA target sequence , 1990, Cell.

[17]  M. Singh,et al.  HIV‐1 tat protein stimulates transcription by binding to a U‐rich bulge in the stem of the TAR RNA structure. , 1990, The EMBO journal.

[18]  B. Guy,et al.  A specific inhibitor of cysteine proteases impairs a Vif-dependent modification of human immunodeficiency virus type 1 Env protein , 1991, Journal of virology.

[19]  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.

[20]  J. Garcia,et al.  Serine phosphorylation-independent downregulation of cell-surface CD4 by nef , 1991, Nature.

[21]  R. Desrosiers,et al.  Importance of the nef gene for maintenance of high virus loads and for development of AIDS , 1991, Cell.

[22]  F. Arenzana‐Seisdedos,et al.  HIV enhancer activity perpetuated by NF-κB induction on infection of monocytes , 1991, Nature.

[23]  T. Okamoto,et al.  Transcriptional activation from the long-terminal repeat of human immunodeficiency virus in vitro. , 1990, Virology.

[24]  C. Cheng‐Mayer,et al.  Differential effects of nef on HIV replication: implications for viral pathogenesis in the host. , 1989, Science.

[25]  A. Israël,et al.  Processing of the precursor of NF-κB by the HIV-1 protease during acute infection , 1991, Nature.

[26]  M. Malim,et al.  Nef protein of human immunodeficiency virus type 1: evidence against its role as a transcriptional inhibitor. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[27]  P. Sharp,et al.  Identification and characterization of a HeLa nuclear protein that specifically binds to the trans-activation-response (TAR) element of human immunodeficiency virus. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[28]  J. Sodroski,et al.  Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat. , 1985, Science.

[29]  E. Fenyö,et al.  Cloning and functional analysis of multiply spliced mRNA species of human immunodeficiency virus type 1 , 1990, Journal of virology.

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

[31]  P. Luciw,et al.  Cellular factors regulate transactivation of human immunodeficiency virus type 1 , 1991, Journal of virology.

[32]  B. Crise,et al.  CD4 is retained in the endoplasmic reticulum by the human immunodeficiency virus type 1 glycoprotein precursor , 1990, Journal of virology.

[33]  B. Berkhout,et al.  TAR-independent activation of the HIV-1 LTR: Evidence that Tat requires specific regions of the promoter , 1990, Cell.

[34]  M. Rosenberg,et al.  Rev-dependent expression of human immunodeficiency virus type 1 gp160 in Drosophila melanogaster cells , 1990, Molecular and cellular biology.

[35]  G. Englund,et al.  A novel HIV-1 isolate containing alterations affecting the NF-κB element , 1991 .

[36]  A Wlodawer,et al.  X-ray crystallographic structure of a complex between a synthetic protease of human immunodeficiency virus 1 and a substrate-based hydroxyethylamine inhibitor. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[37]  I. Ernberg,et al.  HIV-1 regulator of virion expression (Rev) protein binds to an RNA stem-loop structure located within the Rev response element region , 1990, Cell.

[38]  E. Dayton,et al.  Functional analysis of CAR, the target sequence for the Rev protein of HIV-1. , 1989, Science.

[39]  B. Peterlin,et al.  Trans-activation by HIV-1 Tat via a heterologous RNA binding protein , 1990, Cell.

[40]  D M Crothers,et al.  Fragments of the HIV-1 Tat protein specifically bind TAR RNA. , 1990, Science.

[41]  B. Berkhout,et al.  Characterization of a human TAR RNA-binding protein that activates the HIV-1 LTR. , 1991, Science.

[42]  M. Mathews,et al.  Synergy between HIV-1 Tat and adenovirus E1A is principally due to stabilization of transcriptional elongation. , 1990, Genes & development.

[43]  Phillip A. Sharp,et al.  HIV-1 Tat protein trans-activates transcription in vitro , 1990, Cell.

[44]  B. Berkhout,et al.  Tat trans-activates the human immunodeficiency virus through a nascent RNA target , 1989, Cell.

[45]  M. Katze,et al.  The integrity of the stem structure of human immunodeficiency virus type 1 Tat-responsive sequence of RNA is required for interaction with the interferon-induced 68,000-Mr protein kinase , 1991, Journal of virology.