While the heterogeneity of influenza A infections has been understood for some time, the impact of minor strains on overall infection and transmission rates has been underappreciated. Now, a team of researchers led by scientists at New York University’s College of Global Public Health has discovered evidence strongly suggesting that these minor flu variants, which are not typically targeted in vaccines, carry a bigger viral punch than previously realized.
"A flu virus infection is not a homogeneous mix of viruses, but, rather, a mix of strains that gets transmitted as a swarm in the population," explained senior study author Elodie Ghedin, Ph.D., professor of biology and public health at NYU. "Current vaccines target the dominant strains because they are the ones that seem to infect the largest number of individuals. But our findings reveal an ability of minor strains to elude these vaccines and spread the virus in ways not previously known."
The results of this study were published recently in Nature Genetics through an article entitled “Quantifying influenza virus diversity and transmission in humans.”
The investigators examined samples from the 2009 flu pandemic in Hong Kong and found that minor strains are transmitted along with the primary strains—replicating and eluding immunizations.
“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 authors wrote. “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 NYU researchers performed whole genome deep sequencing of upper nasal cavity swabs taken from confirmed 2009 Hong Kong flu cases and their household contacts. This method allowed the research team to not only identify variants in flu strains but also quantify what was being transmitted between infected individuals.
The findings from the study showed, unsurprisingly, that most of the infected carried the dominant virus—H1N1 or H3N2. However, in addition to the dominant strains, all patients carried minor strains and variants of the major and minor strains. Even more surprisingly was how readily these variants were transmitted across the studied individuals.
"The combination of unique data, sequencing approaches, and mathematical methods create a nuanced picture of the transmission of diversity during a pandemic," noted study co-author Benjamin Greenbaum, Ph.D., an assistant professor at the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.
"We were able to look at the variants and could link individuals based on these variants," Dr. Ghedin added. "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."