Inhibition of HIV-1 replication by cyclopentenone prostaglandins in acutely infected human cells. Evidence for a transcriptional block.

Rozera, Carmela; Carattoli, Alessandra; Marco, Alessandra De; Amici, Carla; Giorgi, Colomba; Santoro, M.

doi:10.1172/jci118609

Cited by 70 publications

(62 citation statements)

References 39 publications

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“…4). These results suggest that inhibition of NF-B activation could be responsible for the recently described block of HIV-1 mRNA transcription by cyclopentenone PGs (13).…”

Section: Resultssupporting

confidence: 59%

“…Because NF-B activates immunoregulatory and viral genes (3,4), inhibition of NF-B could be one of the mechanisms involved in the immunosuppressive and antiviral activity of PGs. Inhibition of NF-B activation and of the expression of B-controlled HIV-LTR reporter genes is particularly relevant in view of the recently described block of HIV-1 mRNA transcription by cyclopentenone PGs, which results in a dramatic inhibition of HIV replication in acutely infected cells (13).…”

Section: Resultsmentioning

confidence: 99%

“…11). In HIV-1-infected cells, cyclopentenone PGs were recently shown to act by selectively blocking HIV-1 mRNA transcription (13). In negative strand RNA viruses, the antiviral activity is mediated by selective inhibition of viral protein synthesis and maturation, which has been associated with the turning on of an intracellular defense response and induction of heat shock protein synthesis (14,15).…”

mentioning

confidence: 99%

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Inhibition of nuclear factor κB by prostaglandin A₁: An effect associated with heat shock transcription factor activation

Rossi

Elia

Santoro

1997

Proc. Natl. Acad. Sci. U.S.A.

181

104

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“…4). These results suggest that inhibition of NF-B activation could be responsible for the recently described block of HIV-1 mRNA transcription by cyclopentenone PGs (13).…”

Section: Resultssupporting

confidence: 59%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Inhibition of nuclear factor κB by prostaglandin A₁: An effect associated with heat shock transcription factor activation

Rossi

Elia

Santoro

1997

Proc. Natl. Acad. Sci. U.S.A.

181

104

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“…A single PGA 1 treatment soon after virus infection causes, instead, a dramatic reduction in HIV-1 mRNA levels, which lasts up to 48Ϫ 72 h after infection. The block of viral RNA expression by PGA 1 is reversible and, unless treatment is repeated, HIV-1 RNA starts accumulating in PGA 1 -treated cells to return to control levels by 72Ϫ96 h after infection [9]. We have now shown that, in addition to the previously reported effect on HIV-1 mRNA transcription, PGA 1 also inhibits HIV-1 protein synthesis.…”

Section: Discussionsupporting

confidence: 55%

“…In the case of HIV-1, we have shown that a single PGA 1 treatment started soon after virus adsorption causes a dramatic reduction in HIV-1 RNA levels for a period of 48Ϫ72 h after infection. The block of viral RNA expression by PGA 1 is reversible and, unless treatment is repeated, HIV-1 RNA starts accumulating in PGA 1 -treated cells to return to control levels by 96 h after infection [9]. Since a single PGA 1 treatment was still effective in reducing HIV-1 production at 4Ϫ5 days after infection, we investigated whether PGA 1 could be also affecting viral protein synthesis.…”

Section: Resultsmentioning

confidence: 99%

Induction of the heat‐shock response by antiviral prostaglandins in human cells infected with human immunodeficiency virus type 1

Marco

Carattoli²,

Rozera³

et al. 1998

European Journal of Biochemistry

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Cyclopentenone prostaglandins inhibit the replication of several DNA and RNA viruses, including retroviruses. The antiviral activity has been associated with the induction of a 70-kDa heat-shock protein (HSP70), via activation of the heat-shock transcription factor (HSF) in infected cells. In the present study we investigated the effect of prostaglandin A 1 (PGA 1 ) on the regulation of HSP70 gene expression as well as on viral RNA and protein synthesis in CEM-SS cells during acute infection with human immunodeficiency virus type 1 (HIV-1). We report that HIV-1 infection does not alter HSF activation by PGA 1 , whereas it causes an increase in intracellular HSP70 mRNA levels, as a result of enhanced HSP70 mRNA stability. We also show that, as reported in studies of different virus/host cell models, PGA 1 inhibits HIV-1 replication by acting at multiple levels during HIV-1 infection. In addition to the previously reported block of HIV-1 mRNA transcription, PGA 1 was also found to inhibit viral protein synthesis. These results, together with the fact that prostaglandins are used clinically in the treatment of several diseases, open new perspectives in the search for novel antiretroviral drugs.Keywords : antiviral ; heat-shock factor ; heat-shock protein; human immunodeficiency virus; prostaglandin.Prostaglandins (PGs) function as intracellular signal mediators, participating in the regulation of a variety of physiological and pathological processes in eukaryotes, including inflammation and the febrile response [1], cell proliferation and differentiation [2], cytoprotection [3] and the immune response [4]. Starting from the observation that prostaglandins of the A type inhibit Sendai virus replication in cultured monkey cells [5], it is now well established that prostaglandins containing an A,β-unsaturated carbonyl group in the cyclopentane ring structure (cyclopentenone prostaglandins) possess potent antiviral activity against a wide variety of DNA and RNA viruses (reviewed in [6]). In the case of retroviruses, prostaglandins of the A and J types have been shown to inhibit the replication of human immunodeficiency virus-type 1 (HIV-1) in chronically infected human macrophages, and in a variety of acutely infected human cell lines [7Ϫ9].Even though in the last decade major advances have been made in the identification of the cellular and viral targets of cyclopentenone prostaglandins, the mechanism of their antiviral activity has not yet been completely elucidated. Cyclopentenone prostaglandins appear to function differently from any other known antiviral agent, acting at multiple levels during the virus Correspondence to

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

Brenner

Wainberg

1999

Infect. Dis. Obstet. Gynecol.

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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.

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Inhibition of HIV-1 replication by cyclopentenone prostaglandins in acutely infected human cells. Evidence for a transcriptional block.

Cited by 70 publications

References 39 publications

Inhibition of nuclear factor κB by prostaglandin A₁: An effect associated with heat shock transcription factor activation

Inhibition of nuclear factor κB by prostaglandin A₁: An effect associated with heat shock transcription factor activation

Induction of the heat‐shock response by antiviral prostaglandins in human cells infected with human immunodeficiency virus type 1

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

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Inhibition of HIV-1 replication by cyclopentenone prostaglandins in acutely infected human cells. Evidence for a transcriptional block.

Cited by 70 publications

References 39 publications

Inhibition of nuclear factor κB by prostaglandin A1: An effect associated with heat shock transcription factor activation

Inhibition of nuclear factor κB by prostaglandin A1: An effect associated with heat shock transcription factor activation

Induction of the heat‐shock response by antiviral prostaglandins in human cells infected with human immunodeficiency virus type 1

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

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Product

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Inhibition of nuclear factor κB by prostaglandin A₁: An effect associated with heat shock transcription factor activation

Inhibition of nuclear factor κB by prostaglandin A₁: An effect associated with heat shock transcription factor activation