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H. saimiri tyrosine-kinase interacting protein inhibits Tat function: a prototypic strategy for restricting HIV-1-induced cytopathic effects in immune cells.
Virology. 2006 Sep 01; 352(2):253-67.V

Abstract

Herpesvirus saimiri (HVS)-transformed human T cells become permissive for X4 and R5 strains of human immunodeficiency virus type 1 (HIV-1), evidence that HVS-encoded proteins associated with T cell transformation enhance HIV-1 replication. Analyzing the contribution of transformation-associated bicistronic HVS open reading frames (ORF) to HIV-1 replication revealed expression of the second ORF saimiri transformation-associated protein type C (StpC) conferred the permissive phenotype to T cells. In contrast, expression of the first HVS ORF tyrosine-kinase interacting protein (Tip) in the absence of StpC enhanced restriction of HIV-1 replication in T cell lines and peripheral blood mononuclear cells. Understanding the mechanism whereby Tip enhanced restriction of HIV-1 replication may uncover unique pathways that could be targeted therapeutically. Here we report that Tip restricts HIV-1 replication in a monocyte-derived cell line and restricts reactivation of replication of HIV-1 in a T cell line harboring provirus. In this report, we begin to unravel the molecular underpinnings of Tip-mediated restriction. Tip mediates both lymphocyte-cell-specific kinase (Lck)-dependent and -independent effects on HIV-1 replication. We also provide evidence that Tip-mediated restriction is in part due to inhibition of Tat transactivation of the HIV-1 long terminal repeat (LTR). Expression of Tip in T cells increased activation of Stat1 and Stat3, as well as activation of protein kinase RNA-dependent (PKR/p68) and interferon-gamma production. Taken together, these results provide evidence that Tip restricts HIV-1 replication and reactivation by inhibiting HIV-1 transcription while inducing an intercellular antiviral state. We propose that genetically engineered vectors driving Tip expression could provide a prototypic strategy for restricting HIV-1 replication and reactivation in diverse cell lineages.

Authors+Show Affiliations

Department of Microbiology and Immunology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16780912

Citation

Raymond, Andrea D., et al. "H. Saimiri Tyrosine-kinase Interacting Protein Inhibits Tat Function: a Prototypic Strategy for Restricting HIV-1-induced Cytopathic Effects in Immune Cells." Virology, vol. 352, no. 2, 2006, pp. 253-67.
Raymond AD, Hasham M, Tsygankov AY, et al. H. saimiri tyrosine-kinase interacting protein inhibits Tat function: a prototypic strategy for restricting HIV-1-induced cytopathic effects in immune cells. Virology. 2006;352(2):253-67.
Raymond, A. D., Hasham, M., Tsygankov, A. Y., & Henderson, E. E. (2006). H. saimiri tyrosine-kinase interacting protein inhibits Tat function: a prototypic strategy for restricting HIV-1-induced cytopathic effects in immune cells. Virology, 352(2), 253-67.
Raymond AD, et al. H. Saimiri Tyrosine-kinase Interacting Protein Inhibits Tat Function: a Prototypic Strategy for Restricting HIV-1-induced Cytopathic Effects in Immune Cells. Virology. 2006 Sep 1;352(2):253-67. PubMed PMID: 16780912.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - H. saimiri tyrosine-kinase interacting protein inhibits Tat function: a prototypic strategy for restricting HIV-1-induced cytopathic effects in immune cells. AU - Raymond,Andrea D, AU - Hasham,Muneer, AU - Tsygankov,Alexander Y, AU - Henderson,Earl E, Y1 - 2006/06/15/ PY - 2005/11/30/received PY - 2006/02/09/revised PY - 2006/04/11/accepted PY - 2006/6/20/pubmed PY - 2006/10/6/medline PY - 2006/6/20/entrez SP - 253 EP - 67 JF - Virology JO - Virology VL - 352 IS - 2 N2 - Herpesvirus saimiri (HVS)-transformed human T cells become permissive for X4 and R5 strains of human immunodeficiency virus type 1 (HIV-1), evidence that HVS-encoded proteins associated with T cell transformation enhance HIV-1 replication. Analyzing the contribution of transformation-associated bicistronic HVS open reading frames (ORF) to HIV-1 replication revealed expression of the second ORF saimiri transformation-associated protein type C (StpC) conferred the permissive phenotype to T cells. In contrast, expression of the first HVS ORF tyrosine-kinase interacting protein (Tip) in the absence of StpC enhanced restriction of HIV-1 replication in T cell lines and peripheral blood mononuclear cells. Understanding the mechanism whereby Tip enhanced restriction of HIV-1 replication may uncover unique pathways that could be targeted therapeutically. Here we report that Tip restricts HIV-1 replication in a monocyte-derived cell line and restricts reactivation of replication of HIV-1 in a T cell line harboring provirus. In this report, we begin to unravel the molecular underpinnings of Tip-mediated restriction. Tip mediates both lymphocyte-cell-specific kinase (Lck)-dependent and -independent effects on HIV-1 replication. We also provide evidence that Tip-mediated restriction is in part due to inhibition of Tat transactivation of the HIV-1 long terminal repeat (LTR). Expression of Tip in T cells increased activation of Stat1 and Stat3, as well as activation of protein kinase RNA-dependent (PKR/p68) and interferon-gamma production. Taken together, these results provide evidence that Tip restricts HIV-1 replication and reactivation by inhibiting HIV-1 transcription while inducing an intercellular antiviral state. We propose that genetically engineered vectors driving Tip expression could provide a prototypic strategy for restricting HIV-1 replication and reactivation in diverse cell lineages. SN - 0042-6822 UR - https://www.unboundmedicine.com/medline/citation/16780912/H__saimiri_tyrosine_kinase_interacting_protein_inhibits_Tat_function:_a_prototypic_strategy_for_restricting_HIV_1_induced_cytopathic_effects_in_immune_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(06)00265-0 DB - PRIME DP - Unbound Medicine ER -