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HomeNewsNew Human Genes Controlling HIV Infection Identified By Gladstone Scientists

New Human Genes Controlling HIV Infection Identified By Gladstone Scientists

New Human Genes Controlling HIV – Gladstone Scientists Discovery

Gladstone scientists uncover human genes controlling HIV infection using a large-scale genetic approach.

Viruses can grow only by hijacking their hosts as they are parasites. To sustain the infection, viruses use human proteins to modify and multiply the human cells when it infects a human host. The human host activates defense mechanisms at the same time to fight the infection. At present, most of the viral infection drugs target the virus itself. However, scientists want to develop therapies that are believed less likely to elicit drug resistance like therapies aiming for host proteins instead, or the genes that produce them. For this strategy to be successful, it is crucial to have a detailed understanding of virus-host interactions.

At the Gladstone Institutes, a research team led by Nevan Krogan, Ph.D., Senior Investigator, has been cataloging host proteins that physically bind to virus proteins. The human proteins that the virus uses to infect cells and propagate can be identified by these physical interactions. But how the infection is facilitated by the host proteins working together is not revealed by these interactions.

Krogan and staff scientist David Gordon, Ph.D., along with colleagues at the Mount Sinai School of Medicine, University College Dublin, and at UC San Francisco (UCSF) addressed this gap and have developed a new way to understand how HIV infection in human cells is controlled by the host cells.

Rather than disrupting proteins, this approach involves disrupting host genes. This approach is based on the idea pioneered by Krogan—when you disable the genes in pairs, instead of one by one, you can obtain more information about the proteins they encode and the functions of genes. The team assessed more than 63,000 combinations of human genes associated with HIV infection and they describe a map of the genes controlling HIV infection in human cells.

The vE-MAP

An essential advancement for HIV research in several other ways, the team refers to this map as a viral epistasis map (vE-MAP). A set of genes required for the growth of the virus in human cells, previously unsuspected is uncovered by this map and it can be used to test drugs that disrupt HIV-host interactions or to analyze how different HIV mutants affect host cells.

Krogan said, “The E-MAPs’ principle is that when at once, two genes are disrupted and the impact on the cell is examined, sometimes, we can see the effects that are significantly larger or smaller than predicted from the effect of disrupting one gene.”

The two genes’ functions are related, suggests these unexpected effects. Scientists can find groups of genes with similar patterns of interactions by carrying out these pairwise disruptions across hundreds of genes.

Gordon said, “Thus, you can find all the important genes at once, identifying multiple, distinct networks of genes affecting the process you are studying, instead of finding important genes one at a time.”

AIDS/HIV has no cure so far, even though HIV is one of the best-studied human viruses.  Now through antiretroviral therapy, it is well-controlled. However, in resource-poor countries, antiretroviral therapy is impractical as it is costly. Therefore, the priority is still the search for new means of eradicating or halting the virus.

There were several members of the CNOT family, whose role in HIV biology had never been established before, among the genes that stood out in the vE-MAP. In humans, the authors demonstrated that by suppressing innate immunity in CD4+ T cells, the CNOT complex promotes HIV infection. Krogan said, “The impact of CNOT on innate immunity is a key and in future studies, it will serve as a potential novel therapeutic target.”

Moreover, the vE-MAP uncovered genes that had a great effect when tested together but had little impact when disrupted individually.

For a virus such as HIV/AIDS, which has evolved multiple ways of tapping its hosts’ resources, a promising therapeutic strategy could be combining drugs that target two of these genes at the same time. The vE-MAP approach, could in the future be used to understand novel anti-HIV drugs’ mode of action and to screen them.

Krogan said, “An unprecedented view of how, in human cells, HIV, rewires and hijacks the cellular machinery during infection, is provided by this vE-MAP. To identify and test novel therapies, this will generate many new ideas and avenues.”

Gordon said, “To map out the interface between HIV and human cells, and to uncover new therapeutic avenues, our work is proof-of-principle that the vE-MAP approach is a powerful way. Testing this on other pathogens is our next step.”

New Human Genes Controlling HIV – Gladstone Scientists Discovery – Source

Author : Parthibha HC

Shekhar
Shekhar
Shekhar Suman is the Co-founder of BioTecNika Info Labs Pvt. Ltd. He is an Entrepreneur, Writer, Public Speaker, and a Motivational Coach. In his career, he has mentored more than 100,000+ students toward success in the Biopharma Industry. He heads the BioTecNika Group, which comprises BioTecNika.com, BioTecNika.org, and Rasayanika.com. An avid reader and listener who is passionate about BioSciences. Today Biotecnika is India's largest Biotech Career portal, with over 5 Million subscribers from academia & Industry. It's ranked among the top 50 websites worldwide in the Biology category.
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