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LETTER TO THE EDITOR
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Mutation in RNA viruses: A challenge to effective vaccine development


 Department of Community Medicine, Dr. D. Y. Patil Medical College, Pune, Maharashtra, India

Date of Submission16-Apr-2022
Date of Decision18-May-2022
Date of Acceptance19-May-2022
Date of Web Publication19-Jul-2022

Correspondence Address:
Kavita N Thakur,
Qtr. No. 102, Major Qtrs. R and D E Colony, Vishrantwadi, Pune - 401 115, Maharashtra
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mjdrdypu.mjdrdypu_315_22



How to cite this URL:
Thakur KN, Borah N, Gangurde S, Rathod H. Mutation in RNA viruses: A challenge to effective vaccine development. Med J DY Patil Vidyapeeth [Epub ahead of print] [cited 2022 Nov 30]. Available from: https://www.mjdrdypv.org/preprintarticle.asp?id=351331



The acronym 'VIRUS' in the language of computers stands for – Vital Information Resources Under Siege. We use anti-virus software to safeguard personal documents and to get rid of the virus. Along the same lines, when a microbe or a virus becomes a cause of public health concern then the disease detectives (epidemiologists) use resources to obtain vital information regarding the modus operandi of viruses and recommendations are suggested.

Mutations are essential to evolution. In general, the word 'mutation' evokes fear and much can be sensed from people's perturbation when the news about a new variant being born circulates. In movies, 'mutation' has been linked to devilish alien-looking characters that are ready to consume life and leave the surroundings futile. In reality, mutations are a boringly monotonous aspect of viruses.

Ribonucleic acid (RNA) viruses' replication kit is error-prone due to its RNA polymerase enzyme that lacks the function of proofreading. Therefore, RNA viruses mutate with a very high frequency equal to one mutation per copy of the genome. During every copying cycle, their genomes will accumulate mutations.[1],[2],[3] Mutations can be beneficial, neutral, and deleterious to virus survival [Figure 1]. These cycles can occur in different time frames and may lead to the generation of a diverse virus population within a single infected host. The virus's function is affected by most mutations and is removed by natural selection. Hence, unless selectively advantageous, it will not spread to high frequencies. This explains the birth of new variants.
Figure 1: Mutations in RNA viruses

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The recent pandemic of coronavirus disease 2019 (COVID-19) has been the perfect example of RNA virus mutation. Since December 2020, many COVID-19 variants have come to light with origin from different geographical territories viz. Alpha, Beta, Gamma, and Delta with variable transmissibility.[3],[4],[5]

Severe Acute Respiratory Syndrome Coronavirus 2 is a single-stranded RNA virus having low genome stability, making it more prone to mutation accumulation.

Can we rely completely on vaccines for highly mutating RNA viruses?

Let us take the influenza virus, Hepatitis C virus (HCV), and HIV virus as reference examples.

Vaccines are a powerful tool in the fight against viral variants but they are having a tough time in the arena. Immune responses generated by the vaccine can be less effective against the highly mutating RNA viruses. This scenario is synonymous with flu shots being updated every year. Much can be attributed to Antigenic Drift.[6] The virus “drifts” away from its ancestral strain when mutations accumulate in future generations of the virus. Scientists are attempting to forecast which alterations to presently circulating flu viruses are most likely to occur. They develop a vaccination that will protect them against the virus that has been foretold. The flu vaccine can be effective when the forecast is accurate. Occasionally, the forecast is off and the vaccination fails to protect against disease.

The high genetic variability of the HCV can be attributed to the lack of proofreading function of the NS5B polymerase and the presence of two hypervariable regions in the E2 envelope glycoprotein. HCV mutates nearly one nucleotide per replication cycle. To date around seven major genotypes and many subtypes have been isolated and distinguished phylogenetically. Several HCV vaccine candidates have been produced in recent years, targeting different HCV antigens or using alternative delivery mechanisms, however viral diversity and adaptability are important obstacles to vaccine development.[7]

For a variety of reasons, the acquired immune deficiency syndrome causing human immunodeficiency virus (HIV) virus is very genetically variable. It can duplicate itself billions of times per day.[8] It frequently makes errors while making rapid-fire duplicates of itself, resulting in alterations in its genetic code. The more beneficial the alterations are to the virus's survival, the more likely it will replicate. The potential of HIV to recombine and produce novel variants within an individual is another source of HIV diversity. When a host cell is infected with two different types of HIV, this is what happens. Elements from the two viruses may merge to form a new virus that's a unique blend of the two parents.

The fast progression of HIV has far-reaching ramifications. Anti-HIV drug resistance can develop fast with HIV. It is also difficult to tailor a vaccination to a virus that changes rapidly. Several prospective HIV vaccines have been produced so far, but none have done well enough in clinical trials to warrant approval.


  Conclusion Top


Viruses have a natural tendency to mutate to evolve. Viral genome diversity, which is ultimately defined by mutation rates, has a significant impact on the design of antiviral tactics. Considering this aspect of viruses, developing a vaccine that will protect against all variants of the virus becomes difficult. Rather than focusing solely on the curative modality; integrating promotive, preventive, and curative approaches to combat virus outbreaks in the population will protect the available resources.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Fleischmann WR Jr. Viral genetics. In: Baron S, editor. Medical Microbiology. 4th ed. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 43. Available from: https://www.ncbi.nlm.nih.gov/books/NBK8439/.  Back to cited text no. 1
    
2.
Sanjuán R, Domingo-Clap P. Mechanisms of viral mutation. Cell Mol Life Sci 2016;73:4433-48.  Back to cited text no. 2
    
3.
Duffy S. Why are RNA virus mutation rates so damn high? PLoS Biol 2018;16:e3000003.  Back to cited text no. 3
    
4.
Banerjee A, Mossman K, Grandvaux N. Molecular determinants of SARS-CoV-2 variants. Trends Microbiol 2021;29:871-3.  Back to cited text no. 4
    
5.
Gaurav A, Al-Nema M. Polymerases of coronaviruses: Structure, function, and inhibitors. Viral Polymerases 2019:271-300.  Back to cited text no. 5
    
6.
Centre of Disease Control. Influenza (Flu): How Flu viruses can change. CDC (2021 Sept. 21). Available from: https://www.cdc.gov/flu/about/viruses/change.htm. [Last accessed on 2022 Mar 18].  Back to cited text no. 6
    
7.
Ansaldi F, Orsi A, Schicchi L, Bruzzone B, Icardi G. Hepatitis C virus in the new era: perspectives in epidemiology, prevention, diagnostics and predictors of response to therapy. World J Gastroenterol 2014;20:9633-52.  Back to cited text no. 7
    
8.
Andrews SM, Rowland-Jones S. Recent advances in understanding HIV evolution. F1000Res 2017;6:597. doi: 10.12688/f1000research.10876.1.  Back to cited text no. 8
    


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