Abstract
Genetic differences contribute to variations in the immune response mounted by different individuals to a pathogen. Such differential response can influence the spread of infectious disease, indicating why such diseases impact some populations more than others. Here, we study the impact of population-level genetic heterogeneity on the epidemic spread of different strains of H1N1 influenza. For a population with known HLA class-I allele frequency and for a given H1N1 viral strain, we classify individuals into sub-populations according to their level of susceptibility to infection. Our core hypothesis is that the susceptibility of a given individual to a disease such as H1N1 influenza is inversely proportional to the number of high affinity viral epitopes the individual can present. This number can be extracted from the HLA genetic profile of the individual. We use ethnicity-specific HLA class-I allele frequency data, together with genome sequences of various H1N1 viral strains, to obtain susceptibility sub-populations for 61 ethnicities and 81 viral strains isolated in 2009, as well as 85 strains isolated in other years. We incorporate these data into a multi-compartment SIR model to analyse the epidemic dynamics for these (ethnicity, viral strain) epidemic pairs. Our results show that HLA allele profiles which lead to a large spread in individual susceptibility values can act as a protective barrier against the spread of influenza. We predict that populations skewed such that a small number of highly susceptible individuals coexist with a large number of less susceptible ones, should exhibit smaller outbreaks than populations with the same average susceptibility but distributed more uniformly across individuals. Our model tracks some well-known qualitative trends of influenza spread worldwide, suggesting that HLA genetic diversity plays a crucial role in determining the spreading potential of different influenza viral strains across populations.
Highlights
A central aim of epidemiological studies is to identify factors that place some populations at greater risk of contracting an infectious disease than others [1]
We address this question in a specific case, by modeling the impact of genetic diversity in terms of the human leukocyte antigen (HLA) class-I genotype on the predicted epidemic dynamics of H1N1 influenza
We made use of HLA allele frequencies measured across different ethnicities, focusing on the number of high affinity epitopes presented by individuals within 61 ethnicities and for 81 H1N1 influenza A viral strains isolated in 2009 as well as 85 H1N1 influenza A viral strains isolated in other years
Summary
A central aim of epidemiological studies is to identify factors that place some populations at greater risk of contracting an infectious disease than others [1] Such factors can be associated with each of the three legs of the “epidemiologic triad” for infectious diseases, the combination of an external causative agent, a susceptible host, and an environment that links these two together [2]. Even if the causative agent was unique and environmental factors assumed to be largely common, variations intrinsic to the host can lead to large inhomogeneities in epidemic progression across populations [1, 2] Such variations are ignored in standard formulations of compartment models for infectious diseases, which project all properties of the host onto a small set of states describing the host status. These states are typically taken to be susceptible, infected or recovered, with respect to the progress of the disease [3]
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