On the heels of her remarkable paper tracing influenza evolution in a single host last spring, New York University’s Elodie Ghedin has come out with a new publication in Nature Genetics that offers a higher-resolution view of how the flu spreads through a population.
From lead author Leo Poon at the University of Hong Kong and senior author Ghedin, “Quantifying influenza virus diversity and transmission in humans” reports the results of an international collaboration to track the Hong Kong flu pandemic of 2009.
The authors began with the premise that much about the genetically diverse influenza A virus is unknown, since it has primarily been studied at the population level. That type of approach successfully captures dominant flu strains, but may be limited in its ability to elucidate minor viral variants.
Ghedin and her collaborators used SMRT Sequencing to specifically detect these viral haplotypes in each individual host. “To characterize virus variants that achieve sustainable transmission in new hosts, we examined within-host virus genetic diversity in household donor-recipient pairs from the first wave of the 2009 H1N1 pandemic when seasonal H3N2 was co-circulating,” the team writes, noting that minor variants were found in all patients. “Although the same variants were found in multiple members of the community, the relative frequencies of variants fluctuated, with patterns of genetic variation more similar within than between households.”
The team determined that these minor variants, viewed as complete haplotypes for the first time with long-read sequencing, are more important to flu transmission than was previously believed. This critical finding could shape the future design of flu vaccines, which typically do not target minor variants.
Whole genome sequencing was performed on viral strains captured by nasal swabs from flu patients and their household members during the 2009 pandemic. A phylogenetic analysis detailed the transmission pattern between infected patients, both within and between households in the community. “We were able to look at the variants and could link individuals based on these variants,” Ghedin said in a statement. “What stood out was also how these mixes of major and minor strains were being transmitted across the population during the 2009 pandemic — to the point where minor strains became dominant.”
Read the GenomeWeb article describing this work.