(Yet Another) Factor That Controls HIV Latency

[Inchlingblue]

June 26, 2009

Scientists at the Gladstone Institutes of Virology and Immunology (GIVI) have found another clue that may lead to eradication of HIV from infected patients who have been on antiretroviral therapy. A real cure for HIV has been elusive because the virus can "hide" in a latent form in resting CD4-T cells. By understanding this "latency" effect, researchers can identify ways to reactivate the virus and enable complete clearance by current or future therapies.

Researchers in the laboratory of GIVI Associate Director Eric Verdin, MD have found that methylation of cytosine in the DNA of infected cells is associated with HIV latency and that inhibition of DNA methylation causes the reactivation of latent HIV. These observations offer a potential new strategy for inhibiting HIV latency and reactivating the virus. The discovery was reported in the current edition of PLoS Pathogens.

"While HIV-1 latency is likely to be a multifactorial process, we have shown that inhibiting the methylation of the provirus contributes to an almost complete reactivation of latent HIV-1," said lead author Steven E. Kauder.

The research team, which also included scientists from the University of Utah and Stockholm's Karolinska Institute, developed in vitro models of HIV-1 latency in T cells that harbor a full-length HIV genome. The provirus in the cell lines also encoded a fluorescent marker to illuminate HIV-1 transcriptional activity.

In addition to finding that DNA methylation is a mechanism of latency, the scientists also discovered that a host protein, called methlyl-CpG binding domain protein 2 (MBD2) binds to the methylated HIV DNA and is an important mediator of latency.

"Interfering with methylation greatly potentiates the reactivation of HIV," Kauder said. In this study, the researchers found that the drug 5-aza-2'deoxycytidine (aza-CdR) can inhibit HIV methylation and cause the virus to reactivate.

"Combined with other areas of our investigation into HIV latency, this research provides important new knowledge about the process and opens many new pathways for future study," said Dr. Verdin, senior author of the study.

LINKS:

http://www.scientistlive.com/European-Science-News/Biotechnology/Factor_that_controls_HIV_latency/22764/

http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000495

[brazilianman]

Waking up dormant HIV

www.eurekalert.org/pub.../asfb-wud031609.php

[brazilianman]

Synergistic activation of HIV-1 expression by deacetylase inhibitors and prostratin: implications for treatment of latent infection.


http://www.ncbi.nlm.nih.gov/pubmed/19564922?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=2&log$=relatedarticles&logdbfrom=pubmed

[Inchlingblue]

Waking up dormant HIV

www.eurekalert.org/pub.../asfb-wud031609.php

This link does not go to the article, do you have another one that does?

[newt]

This is, like, so old (like, erm, 1991) - research dept press officers really shouldn't recycle redoing of old science to get an article - matt

[Inchlingblue]

This is, like, so old (like, erm, 1991) - research dept press officers really shouldn't recycle redoing of old science to get an article - matt

I've come across articles that trumpet something as new only to find out it was not, it's very frustrating. I'm curious, what is it specifically that is old here, the finding that methylation of cytosine is associated with HIV latency? Or the role of the host protein MBD2?

[elf]

Protease inhibitors will be drugs of choice for killing the virus in the woken-up cells,
but first they have to find the way how to wake them up  (that is, the virus inside of them)