Ecology and evolution of the flu

Jonathan Dushoff Simon A. Levin Dept of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544-1003, USA. We have all had the flu and we would rather not have it again. Unfortunately, no matter how many times we have battled the high fever, aches and fatigue, we might be unable to escape infection in the next ‘flu season’. Annual flu epidemics are an important cause of mortality, particularly for the elderly and those with chronic illness; and severe flu pandemics – three of which have occurred in the past century – can threaten the lives of even the healthiest individuals. These issues, which represent enormous medical and public health challenges, have deep ecological and evolutionary significance that is only beginning to be appreciated and explored. What is the flu? Influenza (flu) is a respiratory infection in mammals and birds. It is caused by an RNA virus in the family Orthomyxoviridae. The virus is divided into three main types (A, B and C), which are distinguished by differences in two major internal proteins [1] (Fig. 1). Influenza virus type A is the most significant epidemiologically and the most interesting from an ecological and evolutionary standpoint, because it is found in a wide variety of bird and mammal species and can undergo major shifts in immunological properties. Type B is largely confined to humans and is an important cause of morbidity. Little is known about type C, which is not an important source of morbidity. Influenza A is further divided into subtypes based on differences in the membrane proteins hemagglutinin (HA) and neuraminidase (NA), which are the most important targets for the immune system. The notation HhNn is used to refer to the subtype comprising the hth discovered HA protein and the nth discovered NA protein. There are currently two subtypes circulating in humans: H1N1 and H3N2. Subtypes are further divided into strains; each genetically distinct virus isolate is usually considered to be a separate strain. Surprisingly little is known about the transmission of flu, and the importance of airborne transmission relative to droplet transmission remains controversial. However, it seems difficult Influenza (flu) is a common infectious disease, but it is unusual in that the primary timescales for disease dynamics (epidemics) and viral evolution (new variants) are roughly the same. Recently, extraordinarily reliable phylogenetic reconstructions of flu virus evolution have been made using samples from both extant and extinct strains. In addition, because of their public health importance, flu epidemics have been monitored throughout the period over which the phylogenetic trees extend. In parallel with this empirical work, theoretical ecologists have developed mathematical and computational models that elucidate many properties of multistrain systems. In the future, to unravel and interpret the complex interactions between ecological and evolutionary forces on flu dynamics, the documented evolution of the virus must be related to the observed population dynamics of the disease. New theoretical insights are also required to simplify model structures and facilitate predictions that can be tested with accessible data.