How do viruses enter cells? Their infection tactics determine whether they can jump species or start a pandemic

COVID-19, flu, mpox, norovirus diarrhea: how do the viruses that cause these illnesses actually infect you?

Viruses cannot replicate themselves, so they must infect your body’s cells to make more copies of themselves. The life cycle of a virus can therefore be roughly described as: ‘enter a cell, produce more virus, exit, repeat’.

Getting inside a cell, or viral entry, is the part of the cycle targeted by most vaccines, as well as a key barrier for viruses jumping from one species to another. My lab and many others are studying this process to better anticipate and combat emerging viruses.

How viruses enter cells

Different viruses spread in the body in different ways: via airborne droplets, on food, through contact with mucous membranes or by injection. They typically first infect host cells near their site of entry – the cells that line the airways for most airborne viruses – and then stay there or spread throughout the body.

Viruses recognize specific proteins or sugars on host cells and stick to them. Each virus has only one chance to introduce its genome into a cell: if its entry mechanism fails, it risks becoming inactivated. They therefore use several mechanisms to avoid triggering premature entry.

Once the virus has bound to the cell, specific molecules on the cell surface or in the cell’s recycling machinery activate the viral envelope proteins for entry.

One example is the SARS-CoV-2 spike targeted by COVID-19 vaccines. These proteins must modify the cell membrane to allow the viral genome to pass through without killing the cell in the process. Different viruses use different tricks to do this, but most work like cellular secretion (the way cells release materials into their environment) in reverse. Specialized viral proteins help fuse the virus and cell membranes and release the viral core inside the cell.

At this point, the viral genome can enter the cell and begin to replicate. Some viruses use only the cellular machinery to replicate, while others carry parts of their own replication machinery and borrow some parts from the cell. After replicating their genome, viruses assemble the components needed to create new viruses.

Two central questions scientists are studying about virus entry are how your body’s defenses can disrupt it and what determines whether a virus from another species can infect humans.

This animation depicts HIV fusing its membrane with a cell in order to release its contents inside.

Immune defenses against viruses

Your body has a multi-layered defense system against viral threats. But the part of your immune system called the antibody response is generally thought to be most effective at sterilizing immunity, preventing an infection from taking hold instead of just limiting its scope and severity.

For many viruses, antibodies target the part of the virus that binds to cells. This is the case not only for current COVID-19 vaccines, but also for the majority of flu immunity, whether from vaccines or previous infection.

However, some antibodies instead target the entry machinery: rather than preventing the virus from sticking, they prevent it from acting altogether. These antibodies are often more difficult for viruses to escape, but they are difficult to reproduce with vaccines. For this reason, the development of antibodies that inhibit entry into cells has been the goal of many next-generation vaccine efforts.

Species jumping and pandemics

The other key question researchers have about viral entry is how to know when a virus from another species poses a threat to humans. This is particularly important because many viruses are first identified in animals such as bats, birds and pigs before spreading to humans, but it is not clear which ones could cause a pandemic.

The part of viruses that sticks to human cells varies the most between species, while the part that introduces the virus into cells tends to stay essentially the same. Many researchers believe that viruses evolving to better bind to human cells, such as flu viruses that bind to cells in the nose and throat, are among the most important warning signs of risk. of pandemic.

However, coronaviruses – the family of viruses containing SARS-CoV-2 – are prompting a re-examination of this idea. Indeed, several animal coronaviruses can actually bind to human cells, but only a few seem capable of transmitting well between people.

Only time will tell whether researchers need to broaden their pandemic prevention horizons or whether their current prioritization of risky viruses is correct. The only sad reality of pandemic research, like earthquake research, is that there will always be another one – we just don’t know when or where, and we want to be ready.

Provided by The Conversation

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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