While Covid-19 restrictions are being lifted rapidly around the world, we are still reeling from the impact of the last three years. More than 6,8 million deaths from covid-19 have been officially recorded, but the actual figure could be closer to 15 million. The pandemic has caused great suffering and social and economic chaos, and the virus itself is still a clear and present threat: one in five Americans complains of persistent symptoms of "long covid".
Worse, covid-19 is far from the last zoonosis that has the potential to devastate the world's population. Countless other animal viruses have been discovered, but many of them remain poorly understood. Any of them can be the source of the emergence of new viruses in humans, and this most often happens with those from the family of "recurrent" viruses, such as coronaviruses, orthomyxoviruses and filoviruses. When viruses from these families appear in mammals or birds, there is always a risk that they could potentially infect humans. And when that happens, thanks to globalization, these viruses can spread faster than ever before in history.
The key challenge, then, is to discover and identify which viruses pose the greatest risk to humans. If we can detect a new virus in humans in the earliest days of an outbreak, we will have a much better chance of implementing the measures needed to prevent another pandemic. To that end, a recent article in the journal "Science" proposes to establish an experimental process through which researchers can test animal viruses for four key properties that are crucial for infection among humans.
By identifying the viruses that pose the greatest risk for zoonosis (cross-species transmission), we can quickly launch diagnostic tools to detect new human infections. Diagnostics based on serology and polymerase chain reaction (PCR) are currently the most practical solutions for healthcare facilities worldwide. But these methods are designed for specific pathogens, so they are only effective when clinicians and scientists know which pathogens to test for.
An animal virus must have four main biological properties to infect humans: it must use a human version of its cellular entry receptor to gain access to human cells; must use human intracellular proteins to replicate and exit human cells; it must overcome the person's innate immune defenses; it must bypass pre-existing human adaptive immune functions such as antibodies and T cells.
Animal viruses that share most of these properties (such as primate arteriviruses) should be targeted for new diagnostic tools. Such tests can be grouped into regional panels for use in diagnosing unusual and non-human diseases, as well as for monitoring healthy populations for viral surveillance.
The first property of a zoonosis, the ability to enter a human cell, is usually the easiest to study because we can test the surface proteins of an animal virus by engineering it into a reporter virus. (The genome of the reporter virus lacks the genes necessary for viral replication, making it safe for research and surveillance purposes.) Using this method, it was discovered that some poorly studied tibroviruses of the rhabdovirus family are able to enter human cells, although their ability to reproduce within these cells unclear.
The ability to replicate, another biological property that viruses need to infect humans, involves a complex process that requires interaction with numerous intracellular host proteins. And a single incompatibility can prevent an animal virus from multiplying in human cells.
On the third property, research is scarce: how animal viruses interact with human innate immunity beyond the interferon response. It is the first line of defense against viral infections. It functions by creating an intracellular environment that limits viral replication and signals the presence of a viral pathogen to the adaptive arm of the immune system. Further research is needed to determine why, for example, some ebolaviruses can reproduce in human cells but rarely infect humans in the wild. In these cases, there appear to be powerful innate immune mechanisms that protect animals, including humans, from cross-species transmission.
The last property is the ability to overcome existing human adaptive immunity, such as neutralizing antibodies and cytotoxic T cells. Although a person's defenses against one virus can be tested for reactivity against another virus, no one knows how well such cross-neutralization is sufficient to protect people from infection or serious illness if exposed to potentially zoonotic viruses.
To detect epidemics at their onset, clinicians and scientists must be able to track animal viruses in human populations. Yet our healthcare systems currently struggle to provide testing for even well-known viruses. We urgently need greater investment in universal and affordable health care, which would also benefit from improving our capacity to monitor the virus.
But in addition to more comprehensive surveillance protocols and stronger health systems, we also need to address the root causes of zoonoses, such as deforestation, wildlife trade and climate change. While implementing a comprehensive pandemic prevention framework will require significant investment, the cost of doing nothing will certainly be far greater. Population growth, increasing urbanization and pressure on nature, as well as the continuation of regular air traffic mean that epidemics of infectious diseases will continue to plague us.
And that is already happening. New cases of highly pathogenic avian influenza in the United States and other countries are a wake-up call. We must always assume that a new pandemic is much closer than most people believe.
The author is a scientist and expert in infectious diseases; is the chairman and president of the global center for health ACCESS Health International
Copyright: Project Syndicate, 2023.
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