scholarly journals Heat Shock Protein–Based Therapeutic Strategies Against Human Immunodeficiency Virus Type Infection

1999 ◽  
Vol 7 (1-2) ◽  
pp. 80-90 ◽  
Author(s):  
B. G. Brenner ◽  
M. A. Wainberg
Keyword(s):  
Human Immunodeficiency Virus ◽  
Heat Shock ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Nk Cell ◽  
Viral Proteins ◽  
Therapeutic Strategies ◽  
Life Cycles ◽  
Immunodeficiency Virus ◽  
Hiv 1

Heat shock proteins (hsps) and cyclophilins (CypA) are intracellular chaperone molecules that facilitate protein folding and assembly. These proteins are selectively expressed in cells following exposure to a range of stress stimuli, including viral infection. Hsp species are highly immunogenic, eliciting humoral, cytotoxic T lymphocyte (CTL), and natural killer (NK) cell responses against viruses, tumours, and infectious diseases. This review discusses the roles of stress proteins in immunity and viral life cycles, vis-à-vis the development of Hsp-based therapeutic strategies against human immunodeficiency virus type-1 (HIV-1) infection. Cumulative findings are cited implicating the requirement of CypA in HIV-1 replication and formation of infectious virions. Studies by our group show the upregulated expression of hsp27 and hsp70 during single-cycle HIV infections. These species redistribute to the cell surface following HIV-infection and heat stress, serving as targets for NK and antibody-dependent cellular cytotoxicity. Co-immunoprecipitation and Western blot studies show that hsp27, hsp70, and hsp78 complex with HIV-1 viral proteins intracellularly. Hsp70, hsp56, and CypA are assembled into HIV-1 virions. The ability of hsps to interact with HIV-1 viral proteins, combined with their inherent adjuvant and immunogenic properties, indicates that hsps may serve as vehicles for antigen delivery and the design of vaccines against acquired immunodeficiency syndrome. Infect. Dis. Obstet. Gynecol. 7:80–90, 1999.

scholarly journals Infection with Vpr-Positive Human Immunodeficiency Virus Type 1 Impairs NK Cell Function Indirectly through Cytokine Dysregulation of Infected Target Cells

2008 ◽  
Vol 82 (14) ◽  
pp. 7189-7200 ◽  
Author(s):  
Biswanath Majumder ◽  
Narasimhan J. Venkatachari ◽  
Shaylee O'Leary ◽  
Velpandi Ayyavoo
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cell Function ◽  
Nk Cell ◽  
Target Cells ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection has been implicated in impairing various aspects of NK cell function in viremic condition, and several viral factors contribute to these defects. Here, we evaluated the effect of HIV-1 Vpr on NK cell cytolytic function and cytokine (gamma interferon [IFN-γ]) production in the context of infection and exposure. Our data indicate that NK cells derived from a peripheral blood mononuclear cell culture infected in vitro with HIV-1 vpr(+) virus or exposed to recombinant Vpr protein exhibited reduced target cell killing in conjunction with diminished expression of CD107a and reduced IFN-γ production compared to their Vpr-negative counterparts. This Vpr-induced NK cell defect is in part through differential regulation of interleukin-12 and transforming growth factor β production by the infected target cells and concomitant activation of Smad3 signaling pathway. Collectively, these results illustrate the ability of Vpr to impair NK cell-mediated innate immune functions indirectly by dysregulating multiple cytokines in the infected target cells, thus increasing disease severity and affecting the final outcome in HIV-1 infection.

scholarly journals Effect of retinoic acid on HL-60 cells infected with human immunodeficiency virus type 1

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2480-2488 ◽  
Author(s):  
M Semmel ◽  
A Macho ◽  
D Coulaud ◽  
A Alileche ◽  
S Plaisance ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Retinoic Acid ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Viral Proteins ◽  
Mrna Synthesis ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

Abstract HL-60 cells infected with human immunodeficiency virus type 1 (HIV 1) can be induced to differentiate along the granulocyte pathway by retinoic acid. In these cells, HIV mRNA synthesis is stimulated, but synthesis of viral proteins and virus replication are blocked and HIV- infected cells die after becoming apoptotic and/or vacuolized.

scholarly journals Synergistic Activation of Human Immunodeficiency Virus Type 1 Promoter Activity by NF-κB and Inhibitors of Deacetylases: Potential Perspectives for the Development of Therapeutic Strategies

2002 ◽  
Vol 76 (21) ◽  
pp. 11091-11103 ◽  
Author(s):  
Vincent Quivy ◽  
Emmanuelle Adam ◽  
Yves Collette ◽  
Dominique Demonte ◽  
Alain Chariot ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Trichostatin A ◽  
Therapeutic Strategies ◽  
Inhibitory Protein ◽  
Necrosis Factor Alpha ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The transcription factor NF-κB plays a central role in the human immunodeficiency virus type 1 (HIV-1) activation pathway. HIV-1 transcription is also regulated by protein acetylation, since treatment with deacetylase inhibitors such as trichostatin A (TSA) or sodium butyrate (NaBut) markedly induces HIV-1 transcriptional activity of the long terminal repeat (LTR) promoter. Here, we demonstrate that TSA (NaBut) synergized with both ectopically expressed p50/p65 and tumor necrosis factor alpha/SF2 (TNF)-induced NF-κB to activate the LTR. This was confirmed for LTRs from subtypes A through G of the HIV-1 major group, with a positive correlation between the number of κB sites present in the LTRs and the amplitude of the TNF-TSA synergism. Mechanistically, TSA (NaBut) delayed the cytoplasmic recovery of the inhibitory protein IκBα. This coincided with a prolonged intranuclear presence and DNA binding activity of NF-κB. The physiological relevance of the TNF-TSA (NaBut) synergism was shown on HIV-1 replication in both acutely and latently HIV-infected cell lines. Therefore, our results open new therapeutic strategies aimed at decreasing or eliminating the pool of latently HIV-infected reservoirs by forcing viral expression.

Proteases of HIV-1 and MAV Hydrolyze Specifically Human Apo-Hemopexin

2000 ◽  
Vol 65 (7) ◽  
pp. 1191-1197
Author(s):  
Ivan Kluh ◽  
Věra Černá ◽  
Iva Pichová ◽  
Zdeněk Voburka
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Viral Proteins ◽  
Viral Proteases ◽  
Vector Projection ◽  
Immunodeficiency Virus ◽  
Domain Protein ◽  
Hiv 1

The specificities of HIV-1 (Human Immunodeficiency Virus Type 1) and MAV (Myeloblastosis Associated Virus) proteases have been evaluated for their ability to split two-domain protein human apo-hemopexin. Both proteases hydrolyze only one peptidic bond Leu240-Ser241located in the connecting region between two domains. The ability of viral proteases to cleave Leu-Ser bond was confirmed by cleavage of synthetic octapeptide His-Leu-Val-Leu-Ser-Ala-Leu-Thr-NH2covering the susceptible area of human apo-hemopexin. The results demonstrate that the cleavage of Leu-Ser bond is not due to its location in the interdomain region of apo-hemopexin. The cleavable bond Leu-Ser has never been found either in viral or in non-viral proteins. According to the vector projection method this octapeptide was considered as non-hydrolyzable.

scholarly journals Effect of retinoic acid on HL-60 cells infected with human immunodeficiency virus type 1

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2480-2488
Author(s):  
M Semmel ◽  
A Macho ◽  
D Coulaud ◽  
A Alileche ◽  
S Plaisance ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Retinoic Acid ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Viral Proteins ◽  
Mrna Synthesis ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

HL-60 cells infected with human immunodeficiency virus type 1 (HIV 1) can be induced to differentiate along the granulocyte pathway by retinoic acid. In these cells, HIV mRNA synthesis is stimulated, but synthesis of viral proteins and virus replication are blocked and HIV- infected cells die after becoming apoptotic and/or vacuolized.

scholarly journals Heat Shock Perturbs TRIM5α Restriction of Human Immunodeficiency Virus Type 1

2007 ◽  
Vol 82 (5) ◽  
pp. 2575-2579 ◽  
Author(s):  
Jenny L. Anderson ◽  
Edward M. Campbell ◽  
Anna Figueiredo ◽  
Thomas J. Hope
Keyword(s):  
Human Immunodeficiency Virus ◽  
Heat Shock ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Proteasome Inhibitors ◽  
Target Cells ◽  
Restriction Factors ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT TRIM5α restriction factors protect target cells from retroviruses by blocking infection prior to the accumulation of viral reverse transcription (RT) products. Here, we demonstrate that heat shock perturbed owl monkey TRIMCyp and rhesus TRIM5α-mediated restriction of human immunodeficiency virus type 1 (HIV-1) late RT products and 2-long terminal repeat circles. Heat shock partially rescued HIV-1 infection from TRIMCyp restriction, and this rescue became more profound when combined with the presence of the proteasome inhibitor MG132. This indicates that viral RT products rescued from restriction by either heat shock treatment or the presence of MG132 are on a productive pathway, supporting a model in which TRIM5α proteins restrict retroviruses in multiple phases that are differentially sensitive to heat shock and proteasome inhibitors.

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