Viral mutation: Frequently asked questions

Simply put, a mutation is a change in the DNA sequence of an organism. Mutations can occur due to an error in cell division, or it can occur due to exposure to certain chemicals, ionizing radiations, and viral infections.

Every time a living cell divides, it has to copy all of its genetic material (DNA) into the new cell. DNA (deoxyribonucleic acid) codes for everything that happens in our body. It determines your skin colour and the colour of our eyes and how strong your immune system is.

Now, the process of replication is not perfect and is prone to errors, even a single change in the code for a gene can cause the gene to express in a different way - say produce a different protein - or completely stop expressing. If the protein plays an important role in certain metabolic pathway or plays some important function in the body, then the mutation may affect a phenotypic change (which will be noticed physically). For example, in sickle cell anaemia, a single mutation causes a gene to produce a different protein and hence manifest in the form of the sickle cell disease.

Fortunately, most organisms (though not all) have a proofreading mechanism to prevent these mutations or neutralise them if they occur. 

Also, the mutation may not be big enough to change the function of the gene. Even if it is, there is this, various organisms (including humans) have a pair of the same gene. Sometimes a mutation has to be present in both the genes of the pair to be able to be expressed, otherwise, it will just stay latent (will not express) and the person would be otherwise alright but a carrier of the said mutation. The mutation that causes beta-thalassaemia is one such mutation. 

If a mutation occurs in the germline cells - sperm or ova - it can be transferred to the next generation. However, a mutation in any other cell of the body does not pass to the next generation. 

Read more: Immunity to COVID-19 what would it mean 

A virus can become either less or more virulent when it mutates. All organisms try to keep mutations rate low, as the chances of a harmful mutation increase if they are several mutations per generation. However, studies show that the more unfavourable environment an organism is put in, the more likely is it to favour mutation since there is a chance that there will be a beneficial mutation.

RNA viruses especially have an edge over mutation since they code for their own replication machinery so they can to a level optimise mutation to keep up their fitness levels in various environments. This is why RNA viruses can quickly jump hosts (like animals to humans) and evade immune response or get resistant to previously effective drugs.

A mutation can also change the target cell a virus attacks. However, in case of RNA viruses with a small genome, there is a high chance that the mutations accumulate over time and start to reduce the pathogenicity of the virus, to an extent that the virus may just disappear from a population completely.

Read more: Why does SARS-COV-2 attack lungs

Researchers say that the rate of mutations in RNA viruses (even though high) is still kept under the level where it can become lethal to the virus - a concept that is called error threshold. This keeps the virus viable even under selection pressure.

According to an article published in a peer-reviewed journal National Science Reviews, the SARS-COV-2 virus has already evolved into two major types. The ancestral less virulent S type and the modified more virulent L type. 

As per the study, the L-type SARS-COV-2 was present in about 70% of the cases in Wuhan, the rest being the S type. However, after January 2020, the frequency of L type decreased in China (where this study was done). Since there is less pressure on the S-type virus, it has become more prevalent now.

Another study done in China suggested that there are at least 30 different mutations in SARS-COV-2 already. In lab studies, some of these types of SARS-COV-2 have shown the capacity to produce 270 times more viral load than normal. The study is still in the pre-print phase and has not yet been peer-reviewed. 

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This is probably the most common question that a lot of us wonder about and is likely coming from the seasonal nature of flu. However, there isn’t enough evidence so far to say that a change in weather can cause a virus to mutate. 

The reason that influenza virus infections are seen mostly in winters is attributed to the summer holidays in schools (since flu mostly affects children). The fact that people tend to remain indoors in winters in close proximity to each other is also considered to be a driving factor for flu season. Flu has also been seen in the tropics, which are much warmer than the cold temperatures it is believed to spread in. Flu outbreaks have also been seen in summers in some areas, indicating that cold weather may have nothing to do with flu season.

According to a study published in the journal Clinical Microbiology and Infection, suppression of immunity in winters due to lack of vitamin D in humans may be another cause of the seasonal nature of respiratory viral infections.

Read more: COVID-19 myths and facts

Studies show that most likely this would not be the case. A virus, especially RNA virus can have several mutations within a single host. However, in most cases, these mutations somehow have an adverse effect on the ability of the virus to replicate or infect new cells. Such variants are then removed through the process of natural selection. 

Even if mutations are so frequent in RNA viruses, a mutation is only selected if it somehow giving an advantage to the virus. Also, there are several traits of a virus - including its virulence and ability to transmit from one host to another - that needs to be conserved to keep up its ability to survive. These traits are usually coded by more than one genes and hence are less likely to change. It is really rare to see a virus change its transmission mode in a short time. 

Previously, a single sudden mutation in the influenza virus - called an antigenic shift - was what had caused flu outbreaks. However, even in flu, the chances of these shifts is really low. Usually, flu viruses mutate in a more gradual manner, accumulating tiny mutations over time - antigenic drift. Antigenic drift is the reason why we have new flu strains every year for which new flu vaccines are made yearly.

Quite opposite to this, a viral mutation - if it is deleterious enough - may just stop the epidemic completely in its tracks.

Read more: Epidemic vs pandemic what do they mean

Viral strains are genetically different variants of the same virus that are formed as a result of mutations in the original virus. A new strain of the virus may be less infectious than the other or it may have a mechanism to evade the host’s immune system. If a new strain is unrecognizable by the host immune system then it is likely that it can infect a person who had been infected (and treated) by the original strain.

This happens frequently in the influenza virus. Dengue virus also has four different serotypes. A serotype is different from a strain; the former refers to a group of organisms in a species which have the same type and number of antigens. A strain, on the other hand, has both phenotypic and genotypic changes. 

Infection with one serovar of dengue virus can protect you from the infection with the other three serovars up until a few months, but after that, you can get dengue infection from other strains. In fact, the first infection leaves the person more susceptible to a serious second infection from the dengue virus because of the existing antibodies that create inflammation. 

Read more: Can you get COVID-19 twice?

It is entirely possible that a person can get infected with multiple strains of the same virus at a time. In fact, in the case of influenza virus, this type of infection is one of the causes of the development of new strains of the virus. Say, a person is infected with two different types of influenza virus, the new strain would have pieces of genetic material from both the strains of the virus. The new strain might then spread quickly. 

Studies show that the swine flu pandemic (which started in Mexico in 2009) was caused due to this type of strain. The swine flu casing strain was a mix of four different types of flu virus including swine flu, human flu and bird flu.

Viruses are not really living in the true sense of the word. They are nucleic acids (DNA/RNA) wrapped in a protein coating. Viruses also contain some lipids and other substances. Only when a virus enters a living cell can it replicate and make progenies.

Though they are non-living outside a host, as per the Centers for Disease Control and Prevention, USA, certain disinfectants including ethyl and isopropyl alcohol in a concentration of 60-80% can inactivate a lot of viruses. 

Read more: Best disinfectants and clearer to kill coronavirus

Another way to eliminate or eradicate a virus is by improving the immunity of the population against a particular virus. However, for immunity to develop, you have to be first infected or vaccinated against it. 

In the case of SARS, a combination of contact tracing, robust testing and other public health measures are believed to be the cause of the disappearance of the SARS causing virus. Since the chain of transmission was broken (which is being tried for SARS-COV-2 too), the virus could not spread more and just vanished. 

However, experts suggest that SARS still remains a threat as it exists in the wild and there is a chance that the SARS causing virus may mutate and show up in humans once again. Again, even if the SARS virus is hiding somewhere and it somehow mutates, there is a chance that the mutation may not be advantageous to the virus. 

Read more: What is herd immunity and can it work in case of COVID-19?

Drug resistance holds significant clinical relevance when it comes to pathogenic microbes, especially for viruses that tend to mutate quickly. Most antiviral drugs target some step in the replication of the virus. In case proper treatment is taken and the drug is successful in eliminating the virus from a population, then it may not have a chance to develop drug resistance. However, if the virus is not removed completely from the body, it will have an evolutionary pressure to evade the effects of said drugs and become resistant to it. 

Also, studies show that the viral population in some cases may synchronize its replication in such a way that new generations emerge when the drug concentration is lowest in the body. The process is called drug resistance by synchronization. 

Again, specific mutations occur when there is a need for them and not every mutation is a drug-resistance mutation. 

Read more: WHO solidarity trial to find a treatment for COVID-19

A preprint study done in India suggested that the SARS-COV-2 present in India has somehow evolved a bit differently from the strains present in other parts of the world. It has a unique mutation on its spikes which acts as a target for host antiviral-RNA called hsa-miR-27b. As per the study, this hsa-miR-27b can inhibit the replication of HIV and it is possible that this is the reason why anti-HIV drugs are being successful in India, while there are contradictory reports about this drug from around the world. The study further said that the same could be possible for the benefits of antimalarial drugs in India.

However, the study is preliminary and is not even peer-reviewed yet. In any case, more studies will be needed to say anything for sure.

Read more: Is hydroxychloroquine really effective against COVID-19

 A vaccine can be monovalent - providing protection against a single strain of a virus - or it can be multivalent - providing protection against multiple strains of the virus. For example, the measles vaccine is a monovalent vaccine while the polio vaccine is polyvalent.

Influenza vaccines that are developed every year provide resistance against all the strains of the virus circulating in the world in the said year. The flu shot this year (2019) was a quadrivalent vaccine - it had four strains of the virus. 

Polyvalent vaccines have antigens from multiple strains. When exposed to those antigens (through the vaccine) our immune system produces antibodies against them, protecting us from the target microbes in a natural setting.

Read more: Vaccine candidates for COVID-19

Every organism mutates when put under evolutionary pressure to do so - when there is a need to evolve to survive. Viruses that have DNA as their genetic material do not mutate as quickly, in fact, their mutation rate is quite slow -  1 mutation after a few hundred or a few thousand copies. 

However, RNA viruses, like coronaviruses and influenza virus mutate quite rapidly - it could be one mutation per copy of the genome. The major reason for this is the lack of proofreading in the process of RNA copying - which is present in DNA copying process. When the proofreading can’t happen, the mutations persist and are carried to the next generation. 

Viruses can also mutate from damage to the nucleic acid due to the presence of a physical or chemical change, certain host enzymes and the inability to correct errors post replication.

Usually, the mutations that do not affect the ability of the virus to infect the host cells persist in a population.

Studies show that SARS-COV-2 has a proofreading mechanism in its replication process, which has kept a lot of its genome conserved so far.