Quantifying the Fitness Advantage of Polymerase Substitutions in Influenza A/H7N9 Viruses during Adaptation to Humans

PLOS ONE, September 2013

24086684

Judith M. Fonville, David F. Burke, Nicola S. Lewis, Leah C. Katzelnick, Colin A. Russell

Adaptation of zoonotic influenza viruses towards efficient human-to-human transmissibility is a substantial public health concern. The recently emerged A/H7N9 influenza viruses in China provide an opportunity for quantitative studies of host-adaptation, as human-adaptive substitutions in the PB2 gene of the virus have been found in all sequenced human strains, while these substitutions have not been detected in any non-human A/H7N9 sequences. Given the currently available information, this observation suggests that the human-adaptive PB2 substitution might confer a fitness advantage to the virus in these human hosts that allows it to rise to proportions detectable by consensus sequencing over the course of a single human infection. We use a mathematical model of within-host virus evolution to estimate the fitness advantage required for a substitution to reach predominance in a single infection as a function of the duration of infection and the fraction of mutant present in the virus population that initially infects a human. The modeling results provide an estimate of the lower bound for the fitness advantage of this adaptive substitution in the currently sequenced A/H7N9 viruses. This framework can be more generally used to quantitatively estimate fitness advantages of adaptive substitutions based on the within-host prevalence of mutations. Such estimates are critical for models of cross-species transmission and host-adaptation of influenza virus infections.