Heat shock protein-based therapeutic strategies against human immunodeficiency virus type 1 infection

Brenner, Bluma G.; Wainberg, Mark A.

doi:10.1002/(sici)1098-0997(1999)7:1/2<80::aid-idog15>3.0.co;2-m

Cited by 21 publications

(12 citation statements)

References 71 publications

(5 reference statements)

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“…These properties led to the use of HSPs as adjuvants in vaccine development [40]. Several studies indicated that HIV-1 induces the synthesis of some HSPs such as Hsp27 or Hsp70 [41], [42]. Hsp70 is found in virions and might interfere with Vpr functions [42], [43], [44], [45], [46].…”

Section: Introductionmentioning

confidence: 99%

Hyperthermia Stimulates HIV-1 Replication

et al. 2012

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HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42–45°C) and Heat Shock Proteins (HSPs) modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38–40°C) on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C) increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.

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Section: Introductionmentioning

confidence: 99%

Hyperthermia Stimulates HIV-1 Replication

et al. 2012

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“…All other proteins detected in the autoradiogram were unaffected by the infection, and identified by MS as host ATP binding proteins (Appendix S1). We suspected that the 70 kDa protein may be the inducible form of Hsp70, Hsp70i, based on previous reports by others describing induction of the protein following DENV infection (21–25). Western blot analysis with antibodies to Hsp70i confirmed this conclusion (Figs.…”

Section: Resultsmentioning

confidence: 99%

“…These include the stress inducible Hsp70i (also called Hsp72, Hsp70–1, and HspA1A/HspA1B ) as well as the constitutively active form, Hsc70 (19). Hsp70i is present at low levels in unstressed cells; however, expression levels rapidly increase in response to cellular stresses such as heat shock or in response to certain viral infections (21–25). Previous studies have shown that siRNA knockdown of Hsp70 results in decreased DENV RNA copy numbers in supernatants and decreased intracellular DENV load (17).…”

Section: Introductionmentioning

confidence: 99%

An inducible heat shock protein 70 small molecule inhibitor demonstrates anti-dengue virus activity, validating Hsp70 as a host antiviral target

et al. 2016

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An estimated three billion people are at risk of Dengue virus (DENV) infection worldwide and there are currently no approved therapeutic interventions for DENV infection. Due to the relatively small size of the DENV genome, DENV is reliant on host factors throughout the viral life cycle. The inducible form of Heat Shock Protein 70 (Hsp70i) has been implicated as a host factor in DENV pathogenesis, however the complete role remains to be elucidated. Here we further illustrate the importance of Hsp70i in dengue virus pathogenesis and describe the antiviral activity of the allosteric small molecule inhibitor that is selective for Hsp70i, called HS-72. In monocytes, Hsp70i is expressed at low levels preceding DENV infection, but Hsp70i expression is induced upon DENV infection. Targeting Hsp70i with HS-72, results in a dose dependent reduction in DENV infected monocytes, while cell viability was maintained. HS-72 works to reduce DENV infection by inhibiting the entry stage of the viral life cycle, through disrupting the association of Hsp70i with the DENV receptor complex. This work highlights Hsp70i as an antiviral target and HS-72 as a potential anti-DENV therapeutic agent.

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“…The HIV-1 viral protein R (Vpr) plays an important role in viral pathogenesis related in part to its capacity to induce G2 cell cycle arrest and T cell apoptosis [123][124][125][126][127]. In fact, a multicopy suppressor screen in fission yeast using Vpr identified Hsp70 as a suppressor of Vprinduced cell cycle arrest.…”

Section: Hsp70 Action During the Replication Of Mammalian Virusesmentioning

confidence: 99%

Hsp70 Molecular Chaperones: Emerging Roles in Human Disease and Identification of Small Molecule Modulators

Brodsky

Chiosis²

2006

CTMC

188

196

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Molecular chaperones are best known for their ability to aid in the solubilization of mis-folded proteins, and as a result play essential roles in protein folding, degradation, and transport. However, many molecular chaperones also play essential roles in signal transduction cascades. For example, Hsp70 molecular chaperones are a highly conserved, abundant class of chaperones that are found in every species and in nearly every cellular compartment in eukaryotes. In addition to their well-established roles in facilitating protein folding and in the targeting of proteins to organelles and to proteolytic machines, Hsp70s are anti-apoptotic and inhibition of Hsp70 function in some cases is sufficient to induce tumor cell death. Hsp70 function is also vital for the replication of viruses. Based on these data, small molecule Hsp70 modulators might, in principle, be used for the treatment of specific cancers, infections, and protein conformational diseases. In this review, we summarize the structural and functional characteristics of Hsp70 chaperones, and then discuss their roles in cellular physiology. Finally, we will review the recent discovery of small molecules that alter Hsp70 expression and function.

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Heat shock protein-based therapeutic strategies against human immunodeficiency virus type 1 infection

Cited by 21 publications

References 71 publications

Hyperthermia Stimulates HIV-1 Replication

Hyperthermia Stimulates HIV-1 Replication

An inducible heat shock protein 70 small molecule inhibitor demonstrates anti-dengue virus activity, validating Hsp70 as a host antiviral target

Hsp70 Molecular Chaperones: Emerging Roles in Human Disease and Identification of Small Molecule Modulators

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