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The role of hydroxylamine derivatives in HIV infection

  • Novel hydroxylamine derivatives such as Bimoclomol and BGP-15 are non-toxic compounds that have wide therapeutic potential in many pathological conditions. They have been shown to elevate stress protein levels when the cell experiences a stress condition [1]. Elevated stress proteins such as the heat shock proteins (HSPs) in-turn exert their cytoprotective effect, overall protecting the cellular environment in harmful conditions. Naturally, HIV infection is regarded as a stress response initiator, and while HSP70 has been shown to provide some protection against HIV infection, HSP90 was found to promote several steps in the viral replication cycle [2, 3]. Additionally, there is a growing amount of evidence suggesting that many viruses; including HIV, require membrane lipid rafts for entry and release [4], it is still unclear whether or not such compounds actually interact with the membrane, but our preliminary experiments hint to such a possibility. Our aim is to analyze the effect of cellular treatment with these novel compounds, and examine the overall effect of heat shock protein induction in the protection against HIV infection. Moreover, the possibility of membrane raft regions alteration by these molecules is to be explored, as such alteration may indeed be a limiting factor to viral entry and release, opening a new door in the field of HIV therapy.

    References


    1. Judit Hargitaia, Hannah Lewisb, Imre Boros et. al. Bimoclomol, a heat shock protein co-inducer, acts by the prolonged activation of heat shock factor-1, Biochemical and Biophysical Research Communications. 2003.
    2. Sergey Iordanskiy, Yuqi Zhao, Paola DiMarzio, et. al. Heat-shock protein 70 exerts opposing effects on Vpr-dependent and Vpr-independent HIV-1 replication in macrophages. Blood, 2004
    3. Low JS, Fassati A., Hsp90: a chaperone for HIV-1, Parasitology, 2014
    4. Catherine S., Adamson, Eric O. Freed. Novel approaches to inhibiting HIV-1 replication. Antiviral Research, 2010

 


 

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