Scientists have identified a new way
to reactivate latent HIV, which could help overcome one of the biggest
obstacles to finding a cure for the deadly virus. Researchers at the
Gladstone Institutes found that increasing the random activity, or
noise, associated with HIV gene expression – without increasing the
average level of gene expression – can reactivate latent HIV.
When HIV infects an immune cell, it
inserts its genetic material into the DNA of the infected cell. In most
cases, the immune cell’s machinery makes copies of the viral genetic
material, a process known as transcription. This eventually leads to the
production – or expression – of all the components needed to make more
viruses. The new viruses are released from the infected cell and spread
the infection to other immune cells in the body. In some cases, however,
HIV expression goes into a holding pattern and the virus enters a
latent state within the infected immune cell. This means that a small
percentage of HIV hides in infected cells, beyond the reach of even the
most potent drugs.
So we cannot completely eliminate
HIV from the body, and people with HIV infection have to take
antiretroviral drugs (ARVs) for the rest of their lives, researchers
said.
‘Understanding how to reactivate
latent HIV is one of the major challenges we must overcome in order to
find a cure for HIV,’ said Leor Weinberger, senior author of the study. One of the properties of latency that makes it so difficult to address is that it is random in nature.
Random fluctuations in transcription
are unavoidable and a general aspect of life at the single-cell level
and lead to ‘noise’ around the average level of gene expression. The
team tested the counter-intuitive notion that compounds that increase
noise in gene expression could work together with transcriptional
activators to increase overall levels of HIV reactivation.
First, they screened a library of
1,600 compounds using a specialised 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 average GFP gene expression levels. They then combined these
newly identified noise enhancers with known transcription activators in a
cell line that serves as a model for HIV latency. They
found that while the noise enhancers could not cause reactivation on
their own, 75 per cent of them could synergise with activators
Source: PTI
http://www.thehealthsite.com/news/cure-for-hiv-on-the-cards-scientists-discover-a-way-to-kill-hidden-hiv-virus/
