Scientists identify a new way to reactivate latent HIV -
A new study published in Science
A team of scientists from the Gladstone Institute identified a new way of latent HIV is revealed, which could help overcome one of the biggest obstacles to finding a cure for HIV infection. They found that increased random activity, or noise associated with HIV gene expression without increasing the average level of expression of the genes can reactivate latent HIV. Their results were published today in the journal Science .
When HIV infects an immune cell, it inserts its genetic material into the DNA of the infected cell. In most cases, the machinery of the immune cell makes copies of the viral genetic material, a process known as transcription name. This eventually leads to the production or expression of all the components needed to make more viruses. New viruses are released from the infected cell and the spread of infection to other cells of the immune system in the body.
In some cases, however, expression of HIV enters a holding pattern and the virus enters a latent state within the infected cells of the immune system. This means that a small percentage of HIV hides in infected cells, beyond the reach of even the most effective drugs. Consequently, we can not completely eliminate HIV from the body, and people infected with HIV are taking antiretroviral (ARV) drugs for the rest of their lives.
"Understanding how to reactivate latent HIV is one of the great challenges we must overcome to find a cure for HIV," said Leor Weinberger, PhD, research associate at the Gladstone Institute of Virology and . immunology and senior author of the study Roy Dar, PhD, lead author of the study, added: "If we can show the virus itself, we can then use ARVs to eliminate it. this so-called 'shock and kill' approach is very promising, but to date there has unfortunately shown limited success. "
one of latency properties that makes it so difficult to address is it is the random nature or stochastic-in. random fluctuations in transcription are inevitable and a general aspect of life in a single cell and lead to "noise" around the average level of gene expression. HIV happens to have the expression of the unusually noisy gene. Scientists have identified compounds that can activate HIV activating transcription, but these compounds are not very effective, in part because of the noisiness of HIV transcription.
In this study, the team tested the idea of cons-intuitive as compounds that increase the noise in gene expression could work together with transcription activators to increase the overall level of reactivation HIV. The concept borrows from other areas of science like chemistry, where theoretical arguments have long argued that the increase in fluctuations can increase the efficiency of the reactions.
First, they screened a library of 10 compounds using a specialized cell line that produces a green fluorescent protein (GFP) when gene expression is activated. The team identified 85 small molecules that increased noise without changing the average levels of expression of the GFP gene. They then combined these newly identified audio amplifiers with transcriptional activators known in a cell line that serves as a model for HIV latency.
They found that while the noise activators may not cause reactivation of their own, 75 percent of them could in synergy with activators and increase viral reactivation compared to only activator . Indeed, some noise amplifiers doubled reactivation levels when combined with activators. In addition, they found a direct correlation between improved noise and the degree of synergy reactivation; more noise, the greater the effect on reactivation. For the first time, these results show that the noise of expression and reactivation of latent HIV are directly related, and to identify new candidates for the "shock and kill" approach to treatment of latent HIV infection .
strategies to reverse the HIV latency will probably require several cycles of treatment, and these new results suggest that noise enhancing compounds may allow each treatment cycle is more efficient to contract HIV prove. additional screens for improving noise activity may identify compounds that synergize with even better and are more effective activators for the reactivation of the virus to eliminate it for good.
" the implications for the use of noise also extend well beyond reactivation of HIV, since the random cellular activity contributes to a wide range of processes, persistent antibiotics to cancer metastasis, "said Dr. Weinberger . "Thus, this approach could represent a new tool for drug discovery across multiple domains."
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