Systems biology of influenza: understanding multidimensional interactions for personalized prevention and treatment.

Influenza virus infection is a public health threat worldwide. It is urgent to develop effective methods and tools for the prevention and treatment of influenza. Influenza vaccines have significant immune response variability across the population. Most of the current circulating strains of influenza A virus are resistant to anti-influenza drugs. It is necessary to understand how genetic variants affect immune responses, especially responses to the HA and NA transmembrane glycoproteins. The elucidation of the underlying mechanisms can help identify patient subgroups for effective prevention and treatment. New personalized vaccines, adjuvants, and drugs may result from the understanding of interactions of host genetic, environmental, and other factors. The systems biology approach is to simulate and model large networks of the interacting components, which can be excellent targets for antiviral therapies. The elucidation of host-influenza interactions may provide an integrative view of virus infection and host responses. Understanding the host-influenza-drug interactions may contribute to optimal drug combination therapies. Insight of the host-influenza-vaccine interactions, especially the immunogenetics of vaccine response, may lead to the development of better vaccines. Systemic studies of host-virus-vaccine-drug-environment interactions will enable predictive models for therapeutic responses and the development of individualized therapeutic strategies. A database containing such information on personalized and systems medicine for influenza is available at http://flu.pharmtao.com.