1918 and 2009

The 1918 influenza pandemic (the “Spanish Flu”), by some estimates, killed as many as 100 million people in a very short period of time.  The 2009 “Swine Flu” pandemic didnt kill so many, but it spread rapidly and widely across the globe.  Despite that difference, it turns out the two viruses responsible for these pandemics have some important similarities.

Influenza virus has a protein on the surface called hemagglutinin, or HA, which is used to attach to host cells, allowing the virus to then enter and replicate.  HAs change rapidly, which is partly why influenza keeps coming back.  When HA changes, your antibodies dont recognize it so well, so you get sick again.  It turns out that the HAs of 2009 and 1918 are similar on both the sequence and structure level.  There is a small patch on the HA protein that is 95% identical between 1918 and 2009 but only 70% identical to seasonal strains.  Looking only at the 3D structure, among all influenza HAs, the 2009 HA is most similar to the 1918 HA.  The 1918 and 2009 HAs also lack glycosylation at the tip, while seasonal influenza viruses HAs are sugary.

Why is that interesting? An unusual pattern was noted in the 2009 pandemic: elderly people were not as affected as younger people, the reverse of what is usually seen with influenza.  It was proposed that perhaps some people still had immunity to the 1918 virus, which continued to circulate for many years after 1918, and that immunity was cross-protective.  A recent study shows that this indeed seems to be the case.  Mice immunized with the 1918 virus are protected against the 2009 virus.  The converse is also true: if you immunize mice with the 2009 virus, they are protected against the 1918 virus.  That’s pretty impressive when you consider that one season’s vaccine might not protect you from next season’s virus. It seems the immune system cant really tell the difference between these viruses.  Note that it also tells us how long immunity can last!  The next question is, how and why has this HA structure come back?

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16 Responses to 1918 and 2009

  1. daesteban says:

    Certainly there would be a limited number of possible combinations, although these would be very numerous. However, reassortants dont appear all that often, so we are not likely to see too many in our own lifetime. And as long as new people are born, lacking immunity, even old combinations could be successful in an immunologically naive population.

  2. John Moon says:

    I can only suppose that the 1918 virus was lurking around with slight variations and that because the elderly were exposed to this they had cross immunity to the 2009 virus… meaning that the elderly had developed immunity which lasted for a very long time, which is really quite amazing.
    There is also the possibility mentioned that the younger had more of an immune response than the elderly, causing more of an inflammatory response.
    I think that there is a possibility that both causes mentioned are connected in the overall effect on the population.

  3. Estello Raganit says:

    In class, we discussed pigs as sort of a “mixing pot” for different virus strains to be created. As noted previously, I think that eventually, there will come a time where there are no longer any possible variations of the flu. With this post and with the stark similarities noted between the two flus, it seems to me as though different strains of the flu are already showing signs of there coming a time where the possibilities of different strains are running out. For us, I think this would be a good thing as we continue taking seasonal flu shots.

  4. Saumya Bhutani says:

    I find it very interesting that the 1918 flu and swine flu have so much in common! I believe that the HA of the 1918 must have been quite strong thus by natural selection it is only expected that a similar HA will eventually show up again to infect younger generations who do not have immunity to the virus.

  5. Lindsay Kantor says:

    The information in this post was definitely intriguing. It is so interesting to think that immunity to a virus could last for almost 100 years! It is also mind blowing that the 2009 virus was so similar to the 1918 virus, yet significantly less similar to virus strains from the past few years. I suppose that the virus evolved in this way because the bodies of young people today have absolutely no immunity to this strain of the virus, and therefore infection was quite easy. Also, the virus was obviously detrimental to the health of our entire population, considering it caused two large pandemics, even given today’s technology.

  6. Sarah Bekele says:

    I thought that the many similarities between the 1918 and 2009 pandemics were quite fascinating. Both cases showed a high infection rate among younger people. It was noted that young people in 1918 were involved in World War I and were thus subject to high stress and had to share tight living spaces with others, which were optimal conditions for the virus to move about from host to host. Young people in 2009 were probably just as stressed as them, perhaps due to a variety of issues such as stress from school and the economic downturn. These high stress situations would easily allow for the H1N1 virus to spread. Another noted similarity was that at the time of both infections, there was a lack of high inflammatory immune response from the elderly, which prevented death by mucus build up in the lungs. It’s possible we will see this HA structure come up again as soon as there is another period of high stress, since our immune systems are vulnerable at that time, and the virus was successful in both outbreaks in 1918 and 2009.

  7. Elizabeth Doyle says:

    My response to the fact that our bodies “can’t really tell the difference” between the 1918 flu and the 2009 flu was very similar to Dip’s. Though this is obviously a positive effect in this particular case because it gives our bodies immunity against both dangerous viruses, the fact that our bodies cannot differentiate between the two different strains as it can with seasonal viruses is worrying on another level. This is due to the fact that our immune system is not enforcing necessary checks on the differences between substances in our body or lacks the ability to tell the difference between substances in our body on a certain level. This could possibly pose a problem in the future if a different virus develops a structure and sequence similar to proteins the body produces, because the body may not be able to tell the difference between the two, and therefore either destroy the necessary proteins or fail to kill the new, dangerous virus.

    Also, it is remarkable that immunity for that flu can last so long. Our bodies immunity against all diseases is not this long lasting, shown by that fact that booster shots are needed to keep immunity against many diseases. Studying how and why our body has a proclivity to retain immunity against diseases like this flu could be a major step in the world of medicine.

  8. Rose Hendricks says:

    When I read this post initially, it occurred to me that there truly is a silver lining to every cloud. Although last year’s swine flu outbreak was a tragedy for many, it led to the discover that there are similarities between the HA of the 2009 and 1918 viruses that other seasonal strains lack. Therefore, scientists have probably discovered a pattern that occurs in the more catastrophic strains of influenza. Could this knowledge lead to a vaccine that, although not effective against all strains, could combat the most severe strains of flu and prevent a future flu pandemic?

  9. Muderi Aradi says:

    I agree with Justin’s comment about the apparent probability of a cyclical nature of viruses. Obviously, some evolutionary component of the 1918 and 2009 virus was successful in host binding and rapid replicaiton. As portions of generations become infected, whiped out, and immunized, the next generation is susceptible to a virus that the immunized generation was not. With this it is probably likely that viral pandemics with similar HA structures will continue to return intermittently in the future.

  10. Mandy Bekhbat says:

    You said influenza pandemics return as seasonal flu. I’d like to know which of the two is related to mutation: influenza turning into seasonal flu vs. it evolving to a new strain? Vaccination against a pandemic doesn’t seem to protect from seasonal flu, so how do they predict the mutation(?) and develop seasonal flu vaccines?

  11. Michael Carraher says:

    I find it very interesting that in 1918, the people who did die (mostly the young), died because they had a stronger immune system. The stronger immune system caused a stronger inflammatory response, inevitably “drowning”the victim. I also find it interesting that no other strain of influenza has caused an immune response similar to the one in 1918. And you said the 2009 swine flu was very similar to 1918. Why hasn’t this one caused nearly the same effects? The only answer I can think of is better technology to fight it. Or is it just a weaker strain that we have built up immunity to?

  12. Justin Warren says:

    It’ll be interesting to see if these types of similarities become increasingly common; as our historical knowledge of influenza grows over the years, I think that we could easily start seeing patterns of HA arise. There can only be so many functional (and efficient, as Sam pointed out) ways to build the hemagglutinin and so It seems possible that this type of occurrence could start being normal. This would be great for us, since apparently these studies are showing that the resistance to these strains stay with us for quite some time once we’ve come in contact with it.

  13. Sam Brucker says:

    In terms of thinking about why the HA showed up again, that HA obviously was doing something right for the virus both in 1918 and last year. Both of theses outbreaks were both threatening diseases that got out of control. I would infer that it’s not a question of why these two severe strains of Influenza had such similar HAs, but rather a conclusion that this type of HA leads to a kind of Influenza that’s good at what it does.

  14. daesteban says:

    This is in reply to Rachel’s interesting observation about the similarity that neither the 1918 nor the 2009 flu affected the elderly as much as normal. I think there are many factors involved, and any one, several or others that we dont know about are likely in play here. The conditions of 1918 certainly played a role. Because of World War I, young people were being shipped around, stressed, and housed in close quarters. Certainly a good environment for spreading disease. Another factor is the immune response to the infection created severe complications. An overly strong inflammatory response caused severe lung damage, so people with stronger immune systems suffered more lung damage than those with weaker immune systems. It may be that since the immune system weakens as we age, the elderly were spared because they didn’t over-respond. There is some data supporting the overly strong response a major factor in disease with the 1918 flu. (http://www.nature.com/nature/journal/v445/n7125/full/nature05495.html) It may also be possible that the elderly had some prior immunity to an earlier epidemic, that conferred some level of protection that younger people did not have. I dont think we will ever be able to find out if thats true or not though.
    For the 2009 virus, we now know that prior immunity explains at least part of the observation that the elderly were less affected, but I dont if it explains all of it. Other factors could also be at play.

  15. Dip Patel says:

    I find it very interesting that the fact that “the immune system can’t really tell the difference between these viruses” is stated in this post as a positive occurrence. I assumed that since the immune system goes through so much trouble to provide specific immunity against as many viruses imaginable, we would want or at least hope that the body can very precisely tell the difference between various strains of viruses incase each requires a different response to be efficiently combated. However, in this case, it seems better that the body does not see the difference.

    Furthermore, to attempt to respond to the question of “how and why has this HA structure come back,” I would say that perhaps the 1918 viral particles have always been floating around but were not lucky enough to find a host not immune to them. I assume, an unlucky host not immune to the strain caught and was infected by the virus. Unfortunate circumstances might have it that the infected individual came into contact with others not immune to this strain and hence successful transmission occurred. That, I assume is how the structure came back and as to “why”, the answer may be: because most if not all of the younger generation did not have immunity to the HA structure of the 1918 virus.

  16. Rachel Trenchard says:

    You mentioned that the elderly were least affected by the recent swine flu outbreak, apparently because of their cross-protective immunity. Interestingly, the 1918 flu also did not impact the elderly to the same degree as younger adults. Is this just a coincidence or is there something else about the viruses that put younger people at risk?

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