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Cheating Viruses: The Rise of Multipartitism

Can emergence of viral cheats decode multipartitism?

by Anindita Mitra
a close up of a virus

Viruses are tiny pirates that can invade our bodies. They need a host to spring to life; without a host, they have no entity. Their genetic material, commonly called the genome, is like a hidden code that permits them to take over other cells. Their codes can be either single-stranded or double-stranded DNA or RNA

Like pirates, viruses hijack our cells and force them to do their bidding. A common trick they use involves clever genome packaging strategies. They pack their genetic material inside a special envelope called a viral capsid. Thus, understanding the techniques of different viral packaging processes is helpful in the discovery of novel antiviral strategies. This makes combating various virus-borne diseases easier.

The ‘Viral’ Trick

Three peculiar viruses are prominent in the viral kingdom: monopartite, segmented, and multipartite. They are named depending on how each of them packs their genetic material inside the capsid.

  1. Monopartite viruses contain all of their genetic information packed into a single strand, much like reading a book from beginning to end.  

      2. Segmented viruses are like a book series, with each segment representing a different volume of instructions.  These segments have unique information for viruses survival and functioning. 

      3.  Multipartite viruses take their genetic material and break it into numerous separate pieces, like a deck of cards. Each card contains essential instructions that the virus requires. Like shuffling cards, these viruses mix and match their genetic segments to create combinations. When they infect a host, they bring along some of these cards, and the host needs to collect and combine them to decipher the full set of instructions. It’s like having a deck of cards that you can rearrange to get different outcomes.

Why do viruses split genomes and become multipartite?

Multipartite viruses have survived the test of evolution and are present in around 20% of all known viral populations. Scientists have proposed different hypotheses for the evolution of multipartitism. 

According to one hypothesis, many group-level advantages benefit multipartitism. When we work in groups, we can complete complex tasks sooner than when doing the job alone. Similarly, viruses divide their genetic material into parts and assign less complex tasks to each segment. Therefore, the whole job of viral reproduction is done in much less time. 

Another hypothesis mentions that a minimum level of conflict exists between different viral genomes, favoring multipartitism due to less competition. 

However, these proposed hypotheses can only partially explain the evolution of multipartitism. There should be high co-infection rates for the group-level benefits to come into play, i.e., around 100 virus particles should infect a host cell. In nature, the co-infection rates are significantly lower—approximately 2 to 13 virus particles infect per host cell. Furthermore, realistic scenarios show that evolutionary conflicts do exist between different viral genomes within populations. 

a close up of a microscope

Source: Science.org

All these findings called for an alternative hypothesis that proposed that multipartitism could evolve through conflict within genomes. This was driven by the emergence of the cheat hypothesis.

What is a cheat?

Cheats are viruses that have developed techniques to outsmart their opponents. Like cheaters in a game, they can manipulate their environment to their advantage. They lack important genes their counterparts possess, but they find ways to cooperate with other cheats during infection and form alliances to compensate for their deficiencies. It’s like a gang of mischievous friends working together to overcome their individual weaknesses and achieve their goals.

There also exist some full cheats, which encode no genes. Often, it takes help from the virus that contains the full-length original genome. This full-length original wild-type-genome-containing virus is called the cooperative virus. The cheats are more competitive and have a higher fitness score than the wild-type cooperative viruses. Therefore, during a co-infection, all the cheats complement each other and eventually lead to the replacement of the original wild-type virus. 

 Cheating is common among different types of viruses, like defective interfering genomes. These are viruses with short viral genomes, which get generated during most viral replication. These genomes arise every time viral replication occurs due to the deletion of genes caused by defects in viral enzymes. 

Does cheating help viruses?

The cheat hypothesis is more reliable than the other existing hypothesis of multipartitism evolution. This is because the cheats can work and collaborate independently with counterparts of their own choice during a co-infection.  Therefore, the cheat hypothesis does not need any group-level benefits for sustenance. Moreover,  in the real world, it is seen that cheats are largely favored among a diverse group of viruses, thus having high fitness scores. 

Cheat hypothesis: winner or loser?

The natural rate of virus co-infection in hosts is much lower. In nature, the development of multipartite viruses with more than two gene segments is complex. Moreover, the development of full cheats poses problems in the test of evolution. Therefore, researchers tested the cheat hypothesis to determine whether cheats successfully developed multipartitism alone or if other factors were also at play. 

Scientists at Yale University in the United States investigated the theoretical validity of the cheat hypothesis. They proposed a game theory model. The researchers observed that cheating can lead to the emergence of multipartitism in viruses even under conditions mimicking reality.

Theoretical observations showed that cheats lacking essential genes can coexist and assort with each other independently during a coinfection. In doing so, they outcompeted and replaced the original cooperative viruses. This results in a population of viruses with fragmented genomes distributed across multiple encapsidated segments. 

The evolution of multipartitism was observed even without group benefits and at levels of coinfection rates commonly found in natural viral infections. The study also demonstrated that cheating can favor the evolution of viruses with more than two genome segments. Furthermore, the analysis supported the hypothesis that higher rates of cheating correlate with increased rates of multipartitism across different virus lineages. 

Well, as the famous saying goes “Life is like a puzzle; without all the pieces, it’s not complete”. The cheat hypothesis follows the same path when explaining the evolution of multipartitism. The rise of a multipartite viral population has been significantly influenced by cheating. Genes evolve based on their existential competition in nature, thus leading to complex biological systems. Cheating is advantageous to viruses as it can provide faster viral replication and unique genome modification benefits. The emergence of cheats also opened the doors for future research endeavors. Future research may look at the factors that lead to coinfection as well as the existence of multiple genes that can produce cheats

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