AGE OF VIRUS
Down To Earth|November 16, 2020
The much-scorned, dreaded biological entities are also the highly misunderstood beings
SNIGDHA DAS, BANJOT KAUR AND ISHAN KUKRETI

ONCE UPON a time, just as life was taking shape on Earth, there was a free-roaming cell. It was fiercely independent. As time passed, it developed an intimate relationship with another of its kind, which predated LUCA—the last universal cellular ancestor. In the beginning, the relationship was symbiotic. But over the period, as the forefather of LUCA embarked on a journey to acquire complex traits, the primitive roamer opted for a simpler, parasitic life. So much so, that one by one it started renouncing its genes, essential for supporting life, until it was left with a few strands and became indistinguishable from the nonliving. Eventually it was unable to replicate independently and accepted the fate of an obligate intracellular parasite—a virus.

Some scientists would like to narrate this story, of the origin of virus, a little differently. They would like to start from the forefather of LUCA that possessed mobile genetic elements—pieces of genetic material capable of moving around within a genome. This characteristic continues to be part of the modern cell; in fact, in humans about 50 per cent of the genome is thought to be mobile elements. At some point, some of the genome of this primordial cell—forefather of LUCA—acquired a few structural proteins and gained the ability to exit the cell and spread as an infectious agent, or a virus.

Both the narrations are based on the assumption that cells existed before viruses. What if it’s the other way round? Some scientists postulate a scenario in which viruses existed in a pre-cellular world as self-replicating genetic elements—RNS (ribonucleic acid) or DNA (deoxyribonucleic acid) molecules. Over time these units, became more organised, complex and even synthesised proteins required for the formation of their shell, known as capsid.

In that case, viruses may have existed before their hosts in any of the three domains of life form—bacteria and archaea (groups of primitive prokaryotes that do not have a true nucleus or membrane-bound organelles but exhibit distinct characteristics) or multicellular eukaryotes, which include humans.

What if viruses co-evolved with these domains or super-kingdoms? What is evolution of life is actually the story of virus-host co-evolution? Last year, writing in Nature Reviews Microbiology, some scientists have proposed that new groups of viruses have repeatedly emerged at all stages of the evolution of life, often through the displacement of ancestral structural and genome replication genes. (See ‘Theories on origin of virus’.)

Such questions, theories and their variants continue to confound scientists even as they are engaged in the biggest war of our times—the ongoing pandemic caused by SARS-COV-2 continues unabated for about a year now, killing 1.26 million people worldwide and with no definitive cure in sight. In fact, our knowledge of viruses have not evolved much in the past 11,000 years, since these smallest and simplest biological entities carried out their first mass killing in history.

That was the time when our nomadic ancestors had taken up farming and were adjusting to settled life. Rodents, that are natural carriers of several viruses, were becoming part of their immediate ecosystems due to easy availability of grains. (It might be an evolutionary milestone for them as well.) A virus usually prefers limiting itself to the population of a particular species. But somewhere during this frequent interaction with rodents, one poxvirus crossed the species barrier and jumped to humans. It was a landmark event, but with lethal consequences. The pox virus caused smallpox, one of the deadliest viral infections in humans. Over the subsequent years, the virus travelled with humans across the globe killing millions. Fatality was very high as we didn’t have immunity against this “novel”

Ebola

Endemic areas

West Africa

Scare factor A rare but severe, illness with a case fatality rate of over 50 per cent

Yellow fever virus

Endemic areas

Africa, Central and South America

Scare factor

Acute haemorrhagic disease transmitted by infected mosquitoes. The “yellow” refers to the jaundice that affects some patients pathogen. In 1980, following an historic global campaign of surveillance and vaccination, the World Health Assembly declared that smallpox has been eradicated—the only infectious disease against which this distinction has been achieved—but nobody knows for sure whether the virus has ceased to exist.

Millions of years of evolution has caused spectacular changes in our life, but what remains a constant is the occurrence of diseases. And viruses cause most of them, at least the ones that kill the most. Over 150 million people have been killed by diseases caused by viruses in the last one century. Yet we did not acknowledge its existence until the late 19th century. In fact, in 1796 when Edward Jenner created the world’s first vaccine to cure smallpox, he had no idea about the existence of virus

What’s strange is that the first evidence of the existence of viruses came while studying plant diseases, not diseases in humans. In 1857, the Netherlands witnessed a strange contagious disease, affecting up to 80 per cent of the tobacco crops. It took over 20 years for scientists to start studying it. In 1879, plant pathologist Adolf Mayer named it the “mosaic disease of tobacco”.

But he was not able to identify the pathogen as there was no instrument to spot it. That was the first hint that a new and extremely tiny pathogen, much smaller than the microscopic bacteria, could be causing the disease. Then scientists used to employ filtering methods to identify bacteria, but the new pathogen slipped out of these filters.

In 1889, over three decades after studies began on mosaic disease, Dutch microbiologist and botanist Martinus W Beijerinck published his findings, which say the disease agent needed growing leaves to multiply or to infect other plants. Second, when he checked newly infected leaves, he found that with fresh infections the disease agent did not lose its disease-causing power. His conclusion was: the agent could grow on leaves but could not reproduce without them. He named this agent as “contagium vivum fluidum”, or a “contagious, living fluid”. He also gave it a nickname, “virus”. Thus, tobacco mosaic became the first virus to be discovered.

Half a century later in the 1940s, American biochemist, virologist Wendell M Stanley created a crystallised sample of the tobacco mosaic virus that could be seen using X-rays. In 1941, with advancement of the electron microscope, we for the first time saw a virus; the tobacco mosaic virus was rod-shaped, with just five genes and protein. A few years later, Stanley shared the Nobel Prize in Chemistry for creating the crystallised sample. “The way we use ‘virus’ today, he was the first one to bring that term to us in a modern context, and I would give him credit for the beginning of virology,” says plant virologist Karen-Beth Scholthof of Texas A&M University, US.

In humans, the virus causing yellow fever was the first one to be described. After pioneering work in Cuba by epidemiologist Carlos Finlay in 1881, who hypothesised that mosquitoes transmitted the disease, US Army physician Walter Reed in 1901 confirmed how the disease spreads and said that it was caused by a filterable agent found in the blood of infected patients. It took another quarter of a century for scientists to understand that “filterable agent” and isolate the virus. However, the doubt over the existence of virus continued for long. Even during the Spanish Flu (1918- 20), the deadliest pandemic of recent century that killed an estimated 50 million people, the medical fraternity believed that it was caused by bacteria.

VICTIM OF MYOPIA

The major roadblock in understanding virus has been scientific myopia. Scientists for long dismissed it as an arrangement of materials because of its small size and simple structure. Poliovirus has a diameter of 25 to 30 nanometers (nm), roughly 10,000 times smaller than a grain of salt, and has one RNS strand. Larger spherically shaped influenza virus is of 80 nm in diameter, with eight RNS strands. A typical brick-shaped poxvirus may be 200 nm wide and 300 nm long and has a double stranded DNA genome.

To be termed alive an entity must have a few non-negotiable properties. It must have the capacity to grow, reproduce, have internal homeostasis or the ability to maintain a relatively stable internal state that persists despite changes in the world outside, and the ability to perform various metabolic processes. Viruses do not have these properties. They do reproduce but they need host cells for replication.

But usurping the host’s metabolic capacity to produce a new generation of virions, essentially virus particles, which go through the next cycle of reproduction, is a smart strategy. What if this is a way living for viruses?

One can understand this only by untangling the lineage of a virus. But it’s not easy. Since viruses are nothing more than a few short strands of RNS or DNA wrapped in a soft protein shell, they cannot leave behind physical fossils. But viruses do leave a footprint—sometime they transfer their own genes to the host cells while replicating. These genetic codes preserve information from millions of years ago. But Gustavo CaetanoAnollés, who is an expert in the field of evolutionary and comparative genomics and teaches bioinformatics at the University of Illinois at Urbana-Champaign, US, says sequences that encode viral genomes are subject to rapid change. Their high mutation rates can obscure deep evolutionary signals. He and his colleagues have thus been trying to retrace virus’ footprints by analysing folds on its protein shell or capsid.

Caetano-Anollés says these protein folds are better markers of ancient events because their three-dimensional structures can be maintained even as the sequences that code for them begin to change. Using computational methods, he and his colleagues have analysed all of the known folds in 5,080 organisms representing every branch of the tree of life, including 3,460 viruses. They have identified 442 protein folds that are shared between cells and viruses, and 66 that are unique to viruses. Their finding shows that the genomes of viruses harbour an abundance of well characterised virus-specific genes and encode numerous protein structures that carry significantly deep evolutionary information about a pervasive virus-to-cell genetic transfer of cellular innovations. Thus, viruses should be considered drivers of cellular evolution rather than minimalistic genetic parasites. They have played and continue to play major roles in the evolution of the living world, the researchers write in the August 3, 2020 issue of ArcHIVes of Virology.

Zika

Endemic areas

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