CHARACTERIZING INTRA-HOST DIVERSITY OF INFLUENZA VIRUS AND MODELING TRANSMISSION NETWORKS DURING NATURAL EPIDEMICS

Influenza A viruses are characterized by high genetic diversity due to error-prone replication, large population sizes, and strong natural selection. While most of what we know about influenza evolution has come from population scale epidemiological studies based on the analysis of a limited number of consensus sequences, these are limiting for outbreak investigations. The analysis of virus genetic diversity present in an infected host provides a richer genetic fingerprint with which to infer host-to-host virus transmission. Despite the use of animal models to characterize extent of intra-host diversity and what proportion of this diversity that is transmitted between individuals, less is known about these key evolutionary parameters in human populations. To quantify and characterize influenza virus variants that can achieve sustainable transmission in new hosts, we used household donor/recipient pairs of infected individuals from a Hong Kong community during the first wave of the 2009 H1N1 pandemic when seasonal H3N2 was also co-circulating. While the same variants were often found in multiple members of the community during the epidemic, the relative frequencies of variants fluctuate, with patterns of genetic variation more similar within than between households. We estimated the effective population size of influenza A virus across these donor/recipient pairs to be in the range of 100-200 contributing members, which enabled the transmission of multiple virus lineages among individuals, including antigenic variants