Viruses can be finely tuned to their hosts. However, mutations can and have resulted in strains that can jump between animals and humans. Sara Sawyer, a virologist from the BioFrontiers institute of the University of Colorado in Boulder, discussed what a virus must do in order to make the leap between species and a worrying discovery her laboratory made about a possible future threat.
How can animal viruses infect humans
Most animal viruses are not capable of infecting humans. We ingest them all the time and most of them pass right through. To cause us harm, a virus must be able to sneak into our cells and use them as a factory to make more. To do this, animal viruses must use several tricks.
First, they must evade all aspects our immune system. This is no small task. They must also be able to replicate in our cells. It is rare for a virus that has evolved under the selective pressures from an animal host to just pop into a human being and become capable of doing all these things.
Can animal viruses often replicate in human cells?
Almost never. Viruses can interact with hundreds to thousands of host proteins to reproduce themselves. Animal viruses are adapted for use of animal versions of these proteins and not the human ones. In rare cases, an animal virus may be able to replicate in a human cell. This is a concern.
Errors made by viruses copying their genomes are fertile ground for evolution. A replicating virus could accumulate mutations that make it more efficient at using a human cell as a replication facility or better at evading human defenses. Natural selection will favor the successful mutations once the animal virus has infected a human. Some animal viruses will be 50 mutations away from being able to replicate in humans; another might be just one mutation away.
How can you determine if an animal virus is near to jumping over to humans?
To understand which viruses are just a hair away from being able thrive in humans we need to figure out what obstacles the virus must overcome. How many viral-replication steps in humans aren’t working and how many immune blocks are active.
We might first test if the virus can attach to a receptor on human cells in order to gain entry. We can do this by taking a cell from the animal host, knocking out the receptor that the virus uses, and replacing it with the human version. If the virus is able to reproduce at normal levels, it means that it can use the human receptor. If we only get 50% of the expected replication, that tells us that the human version works for this virus, but it’s not ideal. If we don’t see any replication, it means that the virus isn’t able to use the receptor.
We can do the same thing with every protein that we know is important for each task the virus must complete, substituting them one by one. This allows us to identify what is stopping the virus replicating in human cells and to distinguish viruses that only need to overcome one or two obstacles from others that are far away.
Which virus is close to jumping in humans?
Viruses infecting primates are of particular importance. Primate viruses can infect humans because they are able to replicate in a similar physiological environment as ours. We see primate viruses transferring from one person to another all the time.
We recently studied a group of viruses called simian eriviruses. Very little information is available about them. These viruses are very similar to the simian immune deficiency virus that caused the AIDS pandemic and HIV. These simian arteriviruses, like HIV, could be extremely lethal if they were able to jump into human beings (C. J. Warren et.al. Cell https://doi.org/jgnv; 2022).
What did you discover about the ability of simian arteriviruses to jump into humans’ bodies?
Simian Arteriviruses are endemic in some species of African primates. These viruses can cause haemorrhagic fever, death, and other complications in captive-primate facilities. We used simian haemorrhagic fever virus (SHFV) as a representative of this virus family, and first identified CD163 as the receptor it uses to enter cells. We were not happy to find that the virus’ human counterpart was fully functional.
Next, we asked if SHFV could use all of the machinery in a human cell to reproduce. We found human cell lines that could replicate SHFV. In one case, SHFV also produced an astronomical amount of copies of itself. Next, we demonstrated that SHFV appears to be able to resist the interferon reaction, an important component of innate immune system. Our adaptive immune system, including antibodies, is the last item on our list. This would be what would hopefully save us from the worst. Unfortunately, SHFV, like HIV, is a virus against which there is no immunity.
What should we do about it?
We need to monitor for arterivirus infections in humans. These have not been observed at this time. We could, for example, run blood tests on people living in areas of Africa where primates have been endemically infected by arteriviruses. If they do, it would indicate a previous infection. Unfortunately, these viruses do not have antibodies tested yet.