Voidaanko HIV-latenssi eliminoida?

Tätä tutkitaan.
p53 on genomin suojelija, the Guardian of Genome. Miten se suhtautuu retrovirusuhkaan, joka voi muuttaa genomia ja pystyttää genomisen latenssin?
https://www.ncbi.nlm.nih.gov/pubmed/27527606

Virol J. 2016 Aug 16;13(1):141. doi: 10.1186/s12985-016-0595-2.

Highly activated p53 contributes to selectively increased apoptosis of latently HIV-1 infected cells upon treatment of anticancer drugs.

Shin Y¹, Lim H¹, Choi BS¹, Kim KC¹, Kang C¹, Bae YS², Yoon CH³.

Abstract

BACKGROUND:

Despite the successful inhibition of human immunodeficiency virus type 1 (HIV-1) replication by combination antiretroviral therapy, cells latently infected with HIV-1 remaining in patients are a major obstacle for eradication of HIV-1 infection. The tumor suppressor factor p53 is activated by HIV-1 infection, and restricts HIV-1 replication. However, a therapeutic strategy based on p53 activity has not been considered for elimination of latently infected cells.

METHODS:

Apoptotic cells were analyzed using flow cytometry with anti-annexin A5-FITC Ab and PI staining upon treatment of anticancer drugs. The expression and activation of p53 and apoptotic molecules in latently HIV-1-infected T cells were compared using Western blot analysis. The role of p53 in the anticancer drug treatment-induced apoptosis of cells latently infected with HIV-1 was determined by knock-down experiment using siRNA against p53.

RESULTS:

Upon treatment with 5-fluorouracil (5-FU), apoptosis was increased in latently infected ACH2 cells encoding competent p53 compared with uninfected parent A3.01 cells, while the apoptosis of latently infected p53 null J1.1 cells was less than that of uninfected cells. Treatment with 5-FU increased the levels of cleaved caspase-3 and PARP in ACH2 cells compared with uninfected and latently infected p53 null J1.1 cells. The levels of expression and activation of p53 were higher in both latently infected ACH2 and NCHA2 cells than in uninfected cells. Furthermore, the activation levels of p53 in both cells were further increased upon 5-FU treatment. Consistent with p53 status, apoptosis was markedly increased in ACH2 and NCHA2 cells compared with uninfected and latently infected J1.1 cells upon treatment with other anticancer drugs such as doxorubicin and etoposide. Inhibition of p53 in cells with latent HIV-1 infection diminished apoptosis upon 5-FU treatment.

CONCLUSION:

Evidence described here indicate that when treated with anticancer drugs, apoptosis of cells with latent HIV-1 infection was increased via the p53 activation pathway and may provide information for application of anticancer drugs to selectively eliminate HIV-1 reservoirs.

Muistiin 29.12. 2016  
Kommntti: p53 rakenteeltaan on hyvin vaativa molekyyli, iso proteiini, ja sen hyvä muodostuminen geneettisen edellytyksen ollessa normaali, vaattii myös hyvää yleiskunta ja riittävää energian ja proteiinin saamsita.  Se kuuluu kehon luonnollisen immuniteetin aseisiin tarkoituksena varsinkin genomisen integriteetin säilyttäminen.  p53 selektiivistä  aktivointia ei kaiketi ole tarkoituksella vielä käytetty terapiassa  HIV- latenssin eliminoimiseen, vaikka se luonnollisesti on toiminut niissä  tapauksissa joissa latenssi on eliminoitunut jos sellaista on tapahtunut.  Henkilöitten taholta minimaalisin  vaatimus on reinfektion välttö.