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Successful Discovery of Protein that Helps HIV Stay Silent
Date : 2023-07-10
Throughout antiretroviral therapy, HIV quietly hides in the CD4+ T lymphocyte reservoir. CD4+ T lymphocytes are a type of white blood cell that play a role in activating the immune system to fight infection.
The existence of these viral sanctuaries explains why antiretroviral therapy must be continued throughout a patient's lifetime in order to prevent viral replication. According to the World Health Organization, more than 38 million people worldwide were living with HIV by the end of 2021.
In the journal Cell Reports, a research team led by Professor of Medicine Petronela Ancuta and her doctoral student Debashree Chatterjee showed for the first time that a protein called the aryl hydrocarbon receptor (AhR) plays a crucial role in the latency of this virus.
"In our study, we found that AhR, a transcription factor that regulates the expression of certain genes, has an antiviral effect on a patient's CD4+ T cells," Ancuta said. “To help HIV remain silent in reservoir cells, this molecule had an effect on the expression of HIC1, another transcription factor known to suppress HIV replication."
To demonstrate this, the scientists knocked down the expression of AhR using the CRISPR/Cas9 system. They also used drugs that induce or block AhR activation. By neutralizing AhR activity by these two methods, the team observed viral growth occurring in CD4+ T cells from HIV-infected and antiretroviral-treated individuals.
Therefore, the study's first authors, Ancuta and Chatterjee, and colleagues recommend the use of drugs that inhibit AhR activity as a "shock and kill" type of elimination strategy. Once reactivated in the presence of an AhR inhibitor (shock phase), HIV-infected cells are seen by the immune system and can be targeted and killed.
In certain types of cancerous tumors, the AhR pathway is activated by molecules from the environment, such as cigarette smoke, pollutants, or ligands from the gut microbiota and cellular metabolism. The resulting anti-inflammatory activity prevents an adequate antitumor immune response.
"Drugs that block AhR have been used against cancer in clinical trials," said Ancuta, a researcher at the UdeM Teaching Hospital Research Center (CRCHUM). "In further research, we hope to test these inhibitors to see if we can eliminate HIV or substantially reduce the size of the viral reservoir in HIV-infected people who are taking antiretroviral therapy."
To better understand the molecular mechanisms behind this viral latency, Ancuta will continue to collaborate with Carine Van Lint, an HIV transcriptionist at the Free University of Brussels, and Jean-Pierre Routy, professor of medicine at McGill University, to validate this new therapeutic target.
"Today, we have successfully demonstrated in patient cells how this AhR pathway is activated," Ancuta said. "With the help of state-of-the-art technologies such as spatial transcriptomics, we hope to further characterize it specifically in the tissues of people living with HIV. This will allow us to validate this therapeutic target in the context of HIV."
EOMES Protein: Unraveling the Mysteries of Cellular Development
Date : 2024-04-27
In\r\nthe intricate world of cellular development, there are numerous proteins that\r\nplay crucial roles in shaping the destiny of cells. One such protein that has\r\ngarnered significant attention from researchers is EOMES (Eomesodermin). EOMES\r\nis a transcription factor that regulates gene expression and is involved in\r\nvarious cellular processes, including embryonic development, immune response,\r\nand cancer progression. In this blog post, we will delve into the fascinating\r\nworld of EOMES protein and explore its functions, mechanisms, and potential\r\nimplications in human health.
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First\r\ndiscovered in the early 1990s, EOMES was\r\ninitially identified as a critical factor in the development of mesoderm and\r\nendoderm, two of the three primary germ layers in early embryonic development.\r\nIt was found to be essential for the formation of various organs and tissues,\r\nincluding the heart, liver, and pancreas. Further studies revealed that EOMES\r\nacts as a master regulator of cell fate determination, directing the\r\ndifferentiation of stem cells into specific cell types.
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One\r\nof the key mechanisms through which EOMES exerts its influence is by binding to\r\nspecific DNA sequences called enhancers and promoters. By binding to these\r\nregulatory regions, EOMES can either activate or repress the expression of\r\ntarget genes, thereby controlling the fate and function of cells. This ability\r\nto modulate gene expression makes EOMES a crucial player in the intricate dance\r\nof cellular development.
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In\r\naddition to its role in embryonic development, EOMES has also been implicated\r\nin the immune response. It is known to be involved in the differentiation and\r\nfunction of various immune cells, including natural killer (NK) cells and\r\ncytotoxic T lymphocytes (CTLs). EOMES helps these cells acquire their\r\nspecialized functions, such as killing infected or cancerous cells, by\r\nregulating the expression of genes involved in cytotoxicity and immune\r\nsurveillance.
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Interestingly,\r\nrecent studies have also linked EOMES to cancer progression. Aberrant\r\nexpression of EOMES has been observed in various types of cancer,\r\nincluding colorectal, breast, and lung cancer. In some cases, high levels of\r\nEOMES have been associated with poor prognosis and increased metastasis. The\r\nexact mechanisms through which EOMES promotes cancer progression are still\r\nbeing unraveled, but it is believed to be involved in regulating cell\r\nproliferation, invasion, and resistance to therapy.
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Given\r\nits diverse functions and implications in human health, EOMES has become an\r\nattractive target for therapeutic interventions. Researchers are exploring\r\nvarious strategies to modulate EOMES activity, with the aim of developing novel\r\ntreatments for diseases such as cancer and autoimmune disorders. For example,\r\nsmall molecules that can selectively inhibit or activate EOMES could\r\npotentially be used to manipulate immune cell function or disrupt cancer cell\r\ngrowth.
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Furthermore,\r\nunderstanding the intricate regulatory networks involving EOMES could provide\r\nvaluable insights into the mechanisms underlying cellular development and\r\ndisease progression. By deciphering the complex interactions between EOMES and\r\nits target genes, researchers can gain a deeper understanding of how cells\r\nacquire their specialized functions and how dysregulation of these processes\r\ncan lead to disease.
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In\r\nconclusion, EOMES protein is a fascinating molecule that plays a critical role\r\nin cellular development, immune response, and cancer progression. Its ability\r\nto regulate gene expression and direct cell fate determination makes it a key\r\nplayer in shaping the destiny of cells. Further research into the mechanisms\r\nand functions of EOMES could pave the way for novel therapeutic interventions\r\nand provide valuable insights into the intricate world of cellular biology.