OAS1 p46 Sensor locating the hidden place of RNA viruses

Husna, Amity University Kolkata

How can RNA viruses be detected in a cell?

Some species of RNA viruses have the ability to cover themselves, hide inside a cell, and create copies of themselves. Positive-strand RNA viruses like the SARS-CoV-2 virus, flaviviruses (West Nile and Zika), as well as picornaviruses (cause polio and some heart and brain inflammation) can avoid detection by a cell’s immune system till they multiply and increase in numbers. 

After invading a cell, these types of viruses take over part of an intracellular membrane and modify the organelle, which they use as a shelter for replicating themselves. In this way, their viral products are shielded from detection by the host cell’s innate immune sensors. However, a “detective enzyme” might be able to locate them and find their whereabouts. This is because a slight variation in RNA virus’ genomic code could give the capacity to produce a sensor by some people’s cells.

Recent Research (2021): 

A new study has found that an enzyme could specifically target the hiding spots of these RNA viruses. The enzyme, known as oligoadenylate synthetase 1 is a variant of the enzyme oligoadenylate synthetase 1 p46 isoform protein (OAS1 p46). Sensors that belong to the OAS family are prompted by interferon to find out RNA viruses or to locate their hidden place. This strategy to locate these viruses helps the cell to defend themselves against the attack.

Although many researchers have demonstrated the importance of OAS proteins to activate an enzyme that has the ability to cleave viral RNA and block numerous viruses from replicating, very little information is present about how individual OAS proteins could carry out the antiviral activity.

OAS1 p46 protein’s role: 

1. Usually, most of the sensors present in the cell for detecting RNA viruses can position themselves to detect viruses only within the cytosol that is between the nucleus and the outer membrane of the cell. During infection, they could sense the viral RNA which gets accumulated in the cytosol only.
2. However, in contrast, the OAS1 p46 protein isoform positions itself on the endomembrane system (the endoplasmic reticulum and the Golgi apparatus).
3. In addition, the OAS1 p46 isoform gives itself a biochemical tune-up known as prenylation, which in this case, gives this protein the ability to traffic to various membranes. 
4. Amino acids are present at the tail end of the protein which gives additional help to this isoform and also improves its antiviral activity.
5. Moreover, sensors get easy access to the viral replication sites due to the localization of the OAS1 p46 isoform in these membranes. As a result, there’s a stronger antiviral activity against the RNA viruses that use this tactic of hiding in a membrane and rapidly multiply themselves.

Significance of the study: 

1. The virological analysis shows that the OAS1 p46 isoform can combat multiple positive-strand RNA viruses including flavivirus, picornavirus, and SARS-CoV-2.
2. Lab samples from patients affected by COVID-19 were examined by the scientists and it was found that the G allele that produces OAS1p46 protein can protect from severe COVID-19. 
3. They identified a single nucleotide variant in the oligoadenylate synthetase 1 gene which could even predict the severity of COVID-19.

To summarise this study, targeting innate RNA sensors that are localized in the endomembrane system is vital for the antiviral action of OAS1 against those dangerous viruses which replicate themselves and evade the immune system. The results also suggest that SARS-CoV-2 replication could be controlled in the early stages of infection via the actions of the OAS1-p46 isoform. Hence, it is an important factor in reducing the severity of COVID-19 disease.

Also read: Modest eruptions may cascade into a catastrophic disaster

Reference: Medicine, U. of W. S. of. (n.d.). Sensor spies hideouts for ​virus replication inside cell membranes. Retrieved August 17, 2021, from https://phys.org/news/2021-08-sensor-spies-hideouts-virus-replication.html

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Author’s info: Husna is a final year student of BTech Biotechnology at Amity University Kolkata. She is a research enthusiast in Immunology and Immunotherapy but she has a keen interest in various other Bioscience subjects as well. She is constantly focused on improving her knowledge and laboratory skills through various internships. She is a Scientific content writer who has knowledge in diverse backgrounds of Biotechnology.