If there are words that for almost nobody suggest anything positive, surely one of them must be “virus”. To utter this word today is to evoke the great enemy that managed to subjugate humanity in a matter of months. But now more than ever, it is worth remembering that not only can viruses be beneficial, but some also count among our allies in the advancement of science and medicine. Today, viruses are powerful biotechnological tools used as molecular vehicles for vaccines or drugs, but they also provide us with untapped opportunities, such as in the fight against infections.
Apart from the endless scientific debate over whether viruses can be considered living beings, the fact is that they are the most abundant organisms on Earth, with an inconceivable superiority over the rest. Estimates put the total number of viruses on the planet at 1031, a figure so vast that it is hard to name; it would take hundreds of millions of universes like ours to reach the same number of stars. But the vast majority of viruses are harmless to us. In fact, more and more research has revealed that the role of certain viruses can be beneficial to their hosts.
Viruses that protect plants
Some plant viruses boost the resistance of plants to unfavourable environmental conditions, such as drought or cold. One of these, the white clover mosaic virus, which these plants pass on to their offspring, inhibits the formation of nitrogen-fixing nodules when this element is abundant in the soil, saving the plant from a waste of resources. One of the most curious cases is that of a virus that infects a fungus, which in turn lives in symbiosis with a plant. This peculiar ménage à trois allows the plant to grow in active volcanic soil at temperatures of 50°C. At Pennsylvania State University, virus ecologist Marilyn Roossinck has applied this mutualism to other plants such as tomatoes to increase their heat tolerance.
“We don’t always know the details of how viruses work to protect plants, but we know that broad changes in the plant metabolism can happen with virus infection,” Roossinck told OpenMind. “For example, virus-infected plants often have higher levels of sugars that may give them more resistance to drought by acting as an osmoprotectant.” The researcher explains that these properties have not yet been exploited, “probably because people are sceptical of beneficial viruses.” Roossinck is studying the potential use of plant viruses against aphid pests.
Mammal viruses that kill bacteria
Mammals also benefit from the contributions of viruses. Murine norovirus—a digestive pathogen affecting mice, whose human version causes diarrhoea—compensates for the effects of damaged intestinal flora and boosts the immune system in rodents. There are documented cases of how some mammal viruses promote immune resistance against dangerous bacteria such as Listeria or Yersinia pestis, which causes plague. More surprisingly, many viruses have left pieces of their genome in ours throughout evolution and have conferred great benefits on us. Perhaps the most striking case is the so-called env genes of certain retroviruses, which millions of years ago were incorporated into the genome of mammals and enabled the appearance of a great evolutionary invention: the placenta. Syncytin, a protein encoded by an endogenous retroviral gene, allows the cellular fusion that creates the barrier between the mother’s body and the foetus.
One of the functions of viruses that are benign to us is that of those that infect bacteria, called bacteriophages or phages. These viruses are the most numerous in nature, and we are only beginning to discover that their ability to kill bacteria can be advantageous to us. Phages are present in abundance in the mucous membranes of animals, and research is revealing that they can act as a first line of defence against pathogenic bacteria, as well as regulating the expression of bacterial genes involved in digestion.
Given their nature as bacteria killers, the potential usefulness of phages against infection has not gone unnoticed by medicine. In fact, this possibility has been investigated since the discovery of these viruses at the beginning of the 20th century. At the time of the First World War, French-Canadian microbiologist Felix d’Hérelle began to experiment with phages as an antibacterial treatment, but this approach was met with great resistance. The discovery of antibiotics, and the fact that d’Hérelle collaborated with the Soviet Union to create an institute dedicated to phage therapy, led to its abandonment in Europe and America; only the USSR and Nazi Germany, without access to antibiotics, continued down this path.
Turning phage into powerful therapeutic weapons
But today the landscape has changed. “I think there will be increased interest in the use of phages as therapeutic agents,” Andrew Millard, an expert in bacteriophage bioinformatics from the University of Leicester, told OpenMind. There is a powerful reason for this shift: the spread of antibiotic resistance among pathogenic bacteria. “The world is on the cusp of a post-antibiotic era,” Manal Mohammed, a microbiologist at the University of Westminster, told OpenMind. “It is expected that by 2050, ten million people could die each year from antibiotic-resistant bacterial infections.” Mohammed predicts that the problem will only worsen with the current massive use of antibiotics against secondary bacterial infections in COVID-19 patients.
Nevertheless, phage therapy also has its challenges, including “the limited host range of many bacteriophages and the ease of development of bacterial resistance to bacteriophages,” Mohammed summarises. For example, the microbiologist explains that phages that attack Salmonella do not infect Escherichia coli; there are even phages specific to particular Salmonella strains, of which there are more than 2,600. As regards the appearance of resistance, curiously enough, one of the systems that bacteria use to defend themselves against phages is a mechanism that we humans have converted into the genomic editing tool of the 21st century: CRISPR. However, phages are also evolving to combat this resistance with anti-CRISPR systems.
By studying the interactions between bacteria and their viruses, Mohammed hopes to promote the development of phage engineering to turn them into powerful therapeutic weapons. Major agencies such as the US National Institutes of Health (NIH) have joined this research, and the successes are mounting. In 2019, a team of researchers produced a phage that successfully treated an infection of a dangerous resistant bacteria, Mycobacterium abscessus, in a 15-year-old patient with cystic fibrosis and both lungs transplanted. “The key modification was to convert temperate phages (which do not kill bacteria efficiently) into lytic phages, which do kill bacteria efficiently,” University of Pittsburgh biotechnologist Graham Hatfull, co-director of the study, told OpenMind.
“Whether phages can realize their potential as antimicrobials is still unclear,” Hatfull admits. Even beyond the technical and regulatory challenges, Miller points to “public acceptance of using a virus, given the current climate of COVID-19” as a potential obstacle.