Pamodināt HIV un izdzīt no šūnām
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02.08.2015
Viena no atklājuma līdzautoriem Satjī Dandekara no Kalifornijas universitātes Devisā (ASV) teikusi, ka izstrādātājiem ir izdevies atrast brīnišķīgu kandidātu uz HIV modinātāja lomu un līdzekli tā sekojošai iznīcināšanai. Pats svarīgākais, viņa uzsvēra, ka preparāts PEP005 jau apstiprināts lietošanai un tiek izmantots medicīniskajā praksē.
Kā atzīmē zinātnieki, salīdzinoši nesen izdevies noskaidrot, ka imūndeficīta vīrusu var uzveikt divos veidos ar šoka terapiju, vīrusu iznīcinot līdz brīdim, kad tas paguvis ierakties organisma šūnās, vai iemācīties to pamodināt no miega un tad iznīcināt ar to pašu šoka triecienu. Raksta autori atklājuši, ka šo uzdevumu spēs veikt divu zāļu kombinācija pretvēža preparāts PEP005, ko izmanto agrīnu keratozes formu ārstēšanai, un viela JQ1, vīriešu kontacepcijas līdzeklis. Dandekaas un viņas kolēģu eksperiments pierādīja, ka šo vielu maisījums inficētajās šūnās iedarbina īpašas signalizācijas ķēdes, kas dezinformē vīrusu, liek tam sākt dalīties un izkļūt ārpusē. Vīrusa daļu ražošana vidēji palielinājās 15 reizes pat visvairāk nomāktajās HIV populācijās.
Zinātnieki tomēr uzsver, ka viņu panākums vēl nenozīmē pilnīgu uzvaru pār HIV. Lai tas notiktu, ir jāatrisina problēmas otrā daļa, tas ir, jāizstrādā līdzekļi, ar kuriem veikt šoka terapiju. Tās visdrīzāk varētu būt izmantojamās ARV vakcīnas, kas organismam palīdz imūnsistēmā atpazīt un iznīcināt vīrusa daļiņas un ar to inficētās šūnas.
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Source 1: "Synergistic Reactivation of Latent HIV Expression by Ingenol-3-Angelate, PEP005, Targeted NF-kB Signaling in Combination with JQ1 Induced p-TEFb Activation" | Published: July 30, 2015 | Read full article at http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005066 |
Abstract
Although anti-retroviral therapy (ART) is highly effective in suppressing HIV replication, it fails to eradicate the virus from HIV-infected individuals. Stable latent HIV reservoirs are rapidly established early after HIV infection. Therefore, effective strategies for eradication of the HIV reservoirs are urgently needed. We report that ingenol-3-angelate (PEP005), the only active component in a previously FDA approved drug (PICATO) for the topical treatment of precancerous actinic keratosis, can effectively reactivate latent HIV in vitro and ex vivo with relatively low cellular toxicity. Biochemical analysis showed that PEP005 reactivated latent HIV through the induction of the pS643/S676-PKCδ/θ-IκBα/ε-NF-κB signaling pathway. Importantly, PEP005 alone was sufficient to induce expression of fully elongated and processed HIV RNAs in primary CD4+ T cells from HIV infected individuals receiving suppressive ART. Furthermore, PEP005 and the P-TEFb agonist, JQ1, exhibited synergism in reactivation of latent HIV with a combined effect that is 7.5-fold higher than the effect of PEP005 alone. Conversely, PEP005 suppressed HIV infection of primary CD4+ T cells through down-modulation of cell surface expression of HIV co-receptors. This anti-cancer compound is a potential candidate for advancing HIV eradication strategies.
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Source 2: "HIV/AIDS: Scientists Find FDA-Approved Compound Could Flush Out Latent HIV In The Hopes Of Curing Disease" | http://www.hngn.com/articles/114661/20150731/hiv-aids-scientists-find-fda-approved-compound-flush-out-latent.htm |
Patients with HIV sometimes have to stop taking HAART medications due to the toxic effects. The treatment also doesn't completely eradicate latent HIV. This new study, however, is giving some hope a cure could be finally on its way. Researchers from the University of California Davis may have found a compound that could help in "flushing out" HIV completely from a person's system.
Patients with HIV usually undergo highly active anti-retroviral therapy (HAART) to manage their condition and many have benefited from this over the years. However, because HIV's mechanism includes an inactive virus, HAART cannot completely cure and remove the disease.
HAART treatments are also occasionally stopped because of possible long-term risks to toxic substances in medications. So when this happens, the latent virus that have not been detected by the treatments sometimes resurface.
For years, experts have been doing research on how flushing out HIV can serve as a better alternative for HAART. The process for this has been termed as "shock and kill." Finding the right mix of compounds for this, however, has proven to be a huge challenge, but the latest findings may finally bring answers.
"We are excited to have identified an outstanding candidate for HIV reactivation and eradication that is already approved and is being used in patients," said lead author Satya Dandekar of the university's Department of Medical Microbiology and Immunology, according to Medical Express. "This molecule has great potential to advance into translational and clinical studies."
The compound molecule, PEP005, is found in a cancer drug called PICATO, which has been approved by the FDA and is used by many patients already. The compound can work to target latent HIV in the body. What's more, it has only minor side effects and low toxicity, according to Mail Online.
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