We don't want to imagine what happens when a cell is infected with two or more viruses, because the cell is already defenseless against a single virus. But in fact, it is not uncommon for cells to be infected with multiple viruses, and cells are not always defeated.
The first to meet the first to win
As you can imagine, when two viruses meet, there is a fierce firefight between them, because they both need the host's material and energy to support their lives, and when competitors emerge, they naturally have to compete to decide where the turf belongs. In the contest between influenza A virus and rhinovirus, influenza A virus has a slight edge.
Pablo Murcia, a virologist at the University of Glasgow in the UK, led a team that collected clinical samples from 36,157 patients from 2005 to 2013 and tested nucleic acids from 11 respiratory viruses (rhinovirus, human coronavirus, adenovirus, influenza A virus, influenza B virus, etc.) and found that about 8% of them had been co-infected with multiple viruses, which is exactly what they studied.
The researchers used mathematical models to analyze the epidemiological trends of respiratory viruses from 2005 to 2013 and found large seasonal differences in the epidemic peaks of different viruses, which seem to know how to avoid internal conflicts. But if they really can't avoid meeting, when it comes to the need to fight, who is a little more powerful fighter?
The results are somewhat interesting, influenza viruses are the most "aggressive" of all the viruses involved in the comparison, and even close relatives (i.e., H3N2, H1N1 two influenza A virus subtypes and influenza B virus) also have a fight between them, they will suppress each other; while the common cold virus is relatively friendly, they will enhance each other's role when they meet The common cold viruses are relatively friendly, as they enhance each other's effects when they meet. Because of this, when the most "friendly" rhinovirus encounters the most "aggressive" influenza A virus, the rhinovirus loses the most badly. In particular, patients infected with influenza A virus for 2 days were 23% less likely to be infected with rhinovirus, while those infected with influenza A virus for 7 days were 61% less likely to be infected with rhinovirus.
How exactly does the influenza A virus beat the rhinovirus? Researchers speculate that it may be because they compete for the same cell surface receptors, and that influenza A viruses have a greater ability to bind to the receptors and are able to enter the cell first and get a head start. Another idea is that the influenza A virus cooperates with the cell to "betray" the rhinovirus, and that when the influenza A virus infects the cell, it induces the immune system to secrete interferon, which puts the body into an antiviral state. When the rhinovirus invades again, it is destroyed by interferon in advance.
It is not uncommon for the first invading virus to "betray" the later virus, and the coronavirus that causes the common cold will also betray the new coronavirus. Researchers found that people who had previously been infected with the common cold coronavirus had a stronger immune response to the new coronavirus than others, and that immunity to the new coronavirus emerged in some populations. The researchers speculate that it is possible that the common cold coronavirus and the new coronavirus in these patients met in a narrow way, and the two viruses attacked each other and eventually died together, while the human cells were fishing for profits.
Working together to fight the world
Of course, viruses are not always so "aggressive", just like the common cold virus, they can sometimes coexist peacefully in the cell, which is not good news for the cell, because it means that the virus will be more aggressive.
Researchers at Wuhan University found that instead of fighting with the new coronavirus when they met, the influenza A virus worked hand in hand with it to promote infection by the new coronavirus.
The researchers paired several respiratory viruses in pairs and infected several groups of mice to observe the survival of the two viruses in the cells of the mice. It was found that influenza A virus greatly enhanced the infectivity of the new coronavirus, while other respiratory viruses, such as respiratory syncytial virus, parainfluenza virus and rhinovirus, did not have this effect.
Further studies revealed that the enhancing effect of influenza A virus was associated with promoting the expression level of ACE2 protein. If the cells were singly infected with influenza A virus, the expression level of ACE2 increased 2 to 3-fold; if co-infected with influenza A virus and neocoronavirus, the expression level of ACE2 increased 28-fold! And since ACE2 protein is a major receptor for neo-coronavirus to enter host cells, influenza A virus enhances the infectivity of neo-coronavirus.
The unique ability of influenza A virus to enhance the infectivity of neo-coronaviruses suggests that this influenza virus is a key pathogen to be prevented and controlled during the current neo-coronavirus pandemic, and if prevention and control are not done well, people could experience a double whammy of both viruses.
Complementary strengths give birth to new species
In addition to competing or cooperating as separate species, different viruses may "spark a love affair" when they meet in a cell, exchanging genetic material or fusing to produce a new virus.
Viral fusions are more common in homologous viruses. Hepatitis D virus (HDV) is a defective virus that cannot replicate on its own and cannot invade the body on its own, but must be combined with hepatitis B virus (HBV) or HBV first before it can invade the body. Because HDV must rely on the shell of HBV to form its own shell, it can be assembled into a complete HDV, which can then replicate and infect humans. When coronaviruses of the same species spread between animals and populations, genetic exchange and fusion occurs, giving birth to novel coronaviruses; influenza viruses also often fuse with each other, resulting in a variety of mutant viruses. These are all examples of fusion of homologous viruses leading to increased strength.
However, experiments have shown that fusion can also occur between different kinds of viruses. A team from the University of Glasgow, UK, transferred two common human respiratory viruses, influenza A virus and respiratory syncytial virus, into human alveolar cells cultured in vitro and then used electron microscopy to observe the survival of the viruses. They found that the two viruses coexisted peacefully in some alveolar cells, and, by looking closely and classifying these viruses, they also identified a third virus - a chimeric virus that has some structural features of both influenza A virus and respiratory syncytial virus.
The new virus contains gene fragments of both viruses and even expresses surface receptors for both viruses. The new virus was so structurally intact and powerful that when the researchers used the new virus to infect cells that had already been exposed to the influenza A virus and developed resistance, it still successfully attacked the cells. This means that the new virus has the "key" to enter the cell for both the influenza A virus and the respiratory syncytial virus, and when one fails, the other can be used as well, thus making it more powerful than the ancestor of the virus.
Although the above experimental results are mostly simulations or calculations, there are possibilities in life, for example, in winter when the human immune system is weakened and viruses are active, a person may be infected with two or even more viruses at the same time. When the time comes, it is not up to humans to decide what the virus will become. In order to deal with various situations and even new epidemics, we must accelerate the pace of research.
