In a new study, researchers have developed a new way to understand how host cells control HIV infection in human cells.
They described a map of the genes controlling HIV infection in human cells, which they built by assessing more than 63,000 combinations of human genes linked to HIV infection.
The research was conducted by a team of Gladstone Institutes scientists.
Viruses are parasites. The only way they can grow is by hijacking their hosts.
Although HIV is one of the best-studied human viruses and is now well-controlled by antiretroviral therapy, there is no cure for HIV/AIDS.
Moreover, antiretroviral therapy is costly, which can make it impractical in resource-poor countries. The search for new means of halting or eradicating the virus is, therefore, still a priority.
In the study, the team’s new method entails disrupting host genes rather than proteins.
The map, which the team refers to as a viral epistasis map (vE-MAP), is an essential advance for HIV research in several other ways.
For one thing, it uncovers a previously unsuspected set of genes required for the growth of the virus in human cells.
For another, the vE-MAP can be used to analyze how different HIV mutants affect host cells or to test drugs that disrupt HIV-host interactions.
It would be an overwhelming effort to test all combinations of the over 20,000 protein-coding genes in the human genome. Instead, the scientists focused on genes already suspected to influence HIV biology.
In particular, they used the genes encoding a large number of human proteins that the Krogan lab had previously found to bind to HIV proteins.
In all, they included over 350 genes in their analysis and tested over 63,000 pairwise disruptions.
Among the genes that stood out in the vE-MAP were several members of the CNOT family, whose role in HIV biology had never before been established.
The team says the impact of CNOT on innate immunity is a key, yet previously unrecognized, host pathway critical to HIV infection. It will serve as a potential novel therapeutic target in future studies.
For instance, scientists can now study if targeting the CNOT complex with drugs could be a way to help HIV patients fight the infection more effectively.
Furthermore, the vE-MAP uncovered genes that had little impact when disrupted individually, but a great effect when tested together.
Combining drugs that target two of these genes at the same time might thus be a promising therapeutic strategy, especially for a virus such as HIV/AIDS.
The lead author of the study is Senior Investigator Nevan Krogan, Ph.D.
The study is published in Molecular Cell.
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