The adaptability of respiratory viruses

      • Influenza tends to move from hotter countries to colder ones
      • It seems to take a few months to adapt to a new climate
      • CoV-2 replicated independently in the throat and lungs of a single patient
      • The strain in the throat was derived from the lung one
      • These observations give an indication of how rapidly respiratory viruses can adapt to new environments
      • Experiments are needed !

We know that respiratory viruses, including CoV-2, have a high mutation rate (in spite of coronavirus having a proofreading mechanism, which gives it greater fidelity than other RNA viruses such as influenza). However, we don’t yet know how this works out in practice – to what extent do new mutations change the properties of disease within, say, a family, or even within a single individual. In this section, I’m going to focus on two scientific papers, one from 2015, the other very recent, that can shed light on this question.

Here is some data showing the movement of influenza around the world from the 2015 paper, written by Trevor Bedford and his colleagues [1]:

Bedford data

This figure takes a bit of explaining.  The authors have divided the world into 9 regions, and, by analyzing the sequences of viruses that were sampled worldwide over three years, they charted the movement of influenza.  The region where each virus was sampled is color coded, and the colors show where the ancestors of current viruses (in each region) came from as you go back in time.  The right-hand side of each box is only colored with the region’s own color because strains have had no time to move.  As you go to the left the colors show where the ancestral viruses were at the time indicated.  For example, “Yamagata-like” influenza B viruses in India (fourth row, first column) moved very little during the study, with almost all viruses at the end being descended from strains that were also in India at earlier times.  At the other extreme (bottom right box), almost all H3N2 influenza in Australia had come into the country during the previous year.

This figure shows some interesting trends.  For example, we can see that influenza tends to go from hotter countries to colder ones.  For example, a lot of European strains came from India and other hot countries: 32% of Yamagata-like influenza B strains, 17% of Victoria-like B strains, 62% of H3N2 influenza A strains, and 50% of H1N1 A strains that were present in Europe at the end of the study came from strains that were in tropical or subtropical regions one year earlier.  You can also see that in three out of four cases, more strains move from South China to North China than in the opposite direction (indicated by red arrows).  The flow is not in one direction only, however.  European and US strains can also make their way to South China and India, although movement in this direction is less common.

I have suggested that we need a rethink to explain the seasonality of respiratory viruses.  I believe that seasonality is a side-effect of the natural temperature-sensitivity of virtually all respiratory viruses.  However the viruses that exist in tropical regions would need to be less temperature-sensitive in order to replicate, because ambient temperatures are higher there, and people’s noses and throats are therefore warmer.  This suggests that a virus that moved from the Tropics to the temperate regions would show greater virulence, because the cold air encountered there would make it more active.  So the observation that respiratory viruses tend to move from south to north in the Northern Hemisphere would be predicted by this proposal.

However viruses do also move in the other direction, and they seem to adapt to their new climate in both cases quite quickly.  If we assume that it takes two or three months for the virus to adapt, we can explain the seasonality of respiratory viruses, because ambient temperature in temperate regions changes significantly on that timescale.  At the same time we can understand their presence throughout the year in the Tropics because they can adapt to the higher temperatures there in a few months.

This gives us a very rough time-scale for the adaptation of respiratory viruses to high and low ambient temperatures.

What does this adaptation look like on the individual scale?  The more recent paper that I mentioned [2], about CoV-2, by Roman Wölfel and his colleagues, can give us clues.  The authors isolated CoV-2 viruses from patients at 37°C, rather than 33°C, which is the temperature required by some respiratory viruses.  For example, coronavirus was first isolated in 1967 at 33°C [3].  This may imply that CoV-2 is less temperature-sensitive than the 1967 strain, or it may just be that the Vero E2 cells that they used were happier at 37°C, so this temperature was used by default.   The study found that CoV-2, unlike the virus that caused SARS, was able to replicate in the throats of sufferers (as well as in the lungs).  This is consistent with the now well-known observation that the senses of smell and taste are inactivated by Covid, implying that the virus invades sensory cells in the nose and mouth.  All of this suggests that CoV-2 may be more temperature-sensitive than SARS CoV, but less temperature-sensitive than normal “seasonal” coronavirus.

A striking observation from sequence data was that one patient was carrying two distinct lineages, one of which replicated in her throat, the other in her lungs.  The lung strain had the same sequence as earlier patients in the cluster, while the throat sample had a new sequence that was derived from it.  This new sequence spread to the remaining patients in the cluster, who were infected by her.

It would be very interesting to know whether the lung-replicating strain was less temperature-sensitive than the throat one.

[1] Bedford, Trevor, et al. “Global circulation patterns of seasonal influenza viruses vary with antigenic drift.” Nature 523.7559 (2015): 217-220.

[2] Wölfel, Roman, et al. “Virological assessment of hospitalized patients with COVID-2019.” Nature (2020): 1-10.

[3] Bradburne, A. F., M. L. Bynoe, and D. A. Tyrrell. “Effects of a” new” human respiratory virus in volunteers.” British medical journal 3.5568 (1967): 767.


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