HIV armor against cellular defense factors

During a viral infection, our cells produce immunity mediators called interferons, which trigger the production of cellular factors to fight pathogens. A new mechanism for overcoming cellular defenses has been identified: virus (A virus is a biological entity that requires a host cell to use…) immunodeficiency virus (HIV-1) contains chemical changes genome (The genome is the entire genetic material of an individual or a person…) called methylation. They protect the viral genome and delay its degradation by ISG20 nuclease, one of the cellular defense factors. This discovery was published in the journal Study of nucleic acids acting on these modifications of the viral genome opens up the possibility of better control of infection.

Representation of the role of HIV-1 RNA 2’O-methylation in protection against antiviral activity of ISG20. Methylation in HIV-1 RNA promotes viral replication by limiting recognition and degradation of the viral genome by ISG20.
© Priscilla El Kazzi

Despite the development of highly effective antiretroviral therapy, human immunodeficiency virus (HIV-1) remains a challenge. health (Health is a state of complete physical, mental and social well-being and…) primary audience. Its pathogenesis is especially associated with the ability to create persistent infection in cells immune system (The body’s immune system is a coordinated set of elements…) avoiding certain antiviral mechanisms of innate immunity. In this work, a new mechanism that allows HIV-1 to escape from a factor antiviral (Antiviral means a molecule that disrupts the replication cycle of one or more…) was determined. This mechanism triggers modifications of the viral genome called methylation at the 2’OH nucleotide group of the RNA genome on the viral side. On the cell side, ISG20 is a cellular factor, a nuclease capable of degrading interfering foreign RNAs.

Experiments were conducted in vitro showed that the ISG20 nuclease efficiently degrades RNA by mimicking the unmodified HIV-1 genome. However, methylation of the viral genome protects it from any degradation. To demonstrate that resistance to nuclease action favors the virus in the cell, cell lines were infected with viruses whose genomes are more or less rich in methylations.

These experiments showed that viruses with low methylation genomes increase sensitivity to the antiviral factor ISG20. We knew that the genomes of certain viruses, including HIV-1, could be modified to pass (The Passer breed was created by the French zoologist Mathurin Jacques…) ignored by sentinel cell RNA helicases (RIG-I, MDA5). This study shows that, in addition, this modification of the viral genome renders the virus resistant to the antiviral effects of ISG20, thereby enabling infection.

Although it remains to be demonstrated whether this viral evasion mode is a mechanism shared by all RNA-genome viruses, this work reveals a new mechanism that allows viruses to evade early detection by the immune system. These results will provide an opportunity to initiate projects for the development of strategies aimed at stimulating the natural capacity of cells to protect against pathogenic agents.

To know more:
Internal RNA 2’O-methylation in the HIV-1 genome antagonizes ISG20 nuclease-mediated antiviral activity.
El Kazzi, Priscilla; Rabah, Nadia; Chamontin, Celia; Colt, Lina; Ferron, Francois; Debart, Francois; duck (Ducks are waterfowl with a distinctive beak, domesticated or not….), Bruno; Miss Dorothea; Coutard, Bruno; Nisole, Sebastien; Decroly, Etienne.
Nucleic Acids Research, November 2022.

Architecture and function of biological macromolecules – AFMB (CNRS/University of Aix-Marseille)
163, avenue (A boulevard is a big city road. It’s basically planted with trees and a…) Luminy. 13288 Marseille CEDEX 09.

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