The selection pressure of the hierarchy of murine immunity to the influenza A virus
The selection pressure of the hierarchy of murine immunity to the influenza A virus made the second wave of the "Spanish" influenza virulent
This is an attempt to explain the virulence of the "Spanish" influenza pandemic of 1918-1919 with the concept of “hierarchy of immunity.“ The hypothesis indicates that the 2009 influenza pandemic will have virulent second waves. But we might be able to stop them by controlling mice and cats.
Hypothesis
1. A population is graded according to strength of immunity to a novel influenza A virus. In this hierarchy of immunity, those who will not be infected with the virus belong to the uppermost level and those who can be infected with the virus without mutation belong to the lowest level.
2. When the virus spreads, it mutates continually by the selection pressure of the hierarchy of immunity and it spreads from a lower level to the next upper level when it becomes more infectious.
The number of people who can be infected is as follows.
N = N1 - N1i + N2 - N2i + … + Nx - Nxi
N : the number of people who can be infected
N1 : the number of people who belong to the lowest level
N1i : the number of people who are infected in the lowest level
N2 : the number of people who belong to the 2nd lowest level
N2i : the number of people who are infected in the 2nd lowest level
Nx : the number of people who belong to the xth lowest level
Nxi : the number of people who are infected in the xth lowest level
When the virus continues spreading, the number of people who can be infected(N) continues increasing and the virus becomes more and more infectious. Then it begins to spread explosively and the number of people who can be infected (N) decreases rapidly. When most of the infected people recover, new patients of the influenza are seldom seen. This is the end of the first wave.
3. The influenza A virus infects a host in two main ways on mutation, large-droplet infection to the upper respiratory tract and small-particle aerosol infection to lung tissue.
In the first wave, the virus spreads mainly with large-droplet infection and large-droplet infection suppresses small-particle aerosol infection.
4. When the virus spreads explosively at the end of the first wave, both large-droplet infection and small-particle aerosol infection become the most infectious and some healthy young adults may have pneumonia but large-droplet infection still suppresses small-particle aerosol infection.
5. When the virus spreads explosively around the end of the first wave, small-particle aerosol infection becomes infectious enough for the virus to spread to mice.
6. The influenza A virus infects lung tissue of mice mainly with small-particle aerosol, and the selection pressure of the hierarchy of murine immunity promotes mutation on small-particle aerosol infection.
7. The number of mice that can be infected increases and the virus spreads explosively after a few months. Then the virus spreads in humans again. This is the beginning of the second wave.
8. In the second wave, small-particle aerosol infection, which is apt to cause pneumonia, is predominant to large-droplet infection. This is why the second wave is virulent.
An infection route from mice to humans
It wouldn't be difficult for researchers to find mice infected with 2009 influenza (H1N1) virus but it would be difficult to find an infection route from mice to humans. All I can think of is that cats that eat an infected mouse transmit the virus to humans. We might be able to stop the second wave by controlling mice and cats.
Why is the curve of influenza death rates in the 1918 pandemic W-shaped?
The W-shaped curve indicates
(1) many young adults had naturally acquired immunity to the novel influenza virus on large-droplet infection to the upper respiratory tract and they were not infected,
(2) as a result, their immunity was not strong enough to avoid small-particle aerosol infection to lung tissue when the second wave came and many of them died.
(3) naturally acquired immunity to the novel influenza virus on large-droplet infection to the upper respiratory tract becomes stronger with age but after 35, it becomes weaker with age.
References
1. Jeffery K. Taubenberger*Comments and David M. Morens: 1918 Influenza: the Mother of All Pandemics
2. World Health Organization (WHO) Writing Group: Nonpharmaceutical Interventions for Pandemic Influenza: Transmission Characteristics of Influenza Viruses