Influenza C in Lancaster, UK, in the winter of 2014-2015

Abstract

Influenza C is not included in the annual seasonal influenza vaccine, and has historically been regarded as a minor respiratory pathogen. However, recent work has highlighted its potential role as a cause of pneumonia in infants. We performed nasopharyngeal or nasal swabbing and/or serum sampling (n = 148) in Lancaster, UK, over the winter of 2014-2015. Using enzyme-linked immunosorbent assay (ELISA), we obtain seropositivity of 77%. By contrast, only 2 individuals, both asymptomatic adults, were influenza C-positive by polymerase chain reaction (PCR). Deep sequencing of nasopharyngeal samples produced partial sequences for 4 genome segments in one of these patients. Bayesian phylogenetic analysis demonstrated that the influenza C genome from this individual is evolutionarily distant to those sampled in recent years and represents a novel genome constellation, indicating that it may be a product of a decades-old reassortment event. Although we find no evidence that influenza C was a significant respiratory pathogen during the winter of 2014-2015 in Lancaster, we confirm previous observations of seropositivity in the majority of the population. (170 words).

Figure 1. Anti-influenza C IgG concentration (mg/dl), plotted for each individual against age.

Blue: >2 standard deviations above negative control; green: 1–2 standard deviations above negative control; red: <1 standard deviation above negative control.

Figure 2. Root-to-tip distance in a neighbour joining tree for segment 1 (encoding PB2) of the influenza C genome.

100 full-length or near full-length genome segments (2365 bases) are used plus the 724 discontinuous bases of segment 1 derived from deep sequencing. C/Lancaster/1/2015 has a degree of divergence from the root consistent with molecular clock-like behaviour in its lineage.

Figure 3. Root-to-tip distance in a neighbour joining tree for segment 6 (encoding M1/CM2) segment of the influenza C genome.

86 full-length or near full-length genome segments (1180 bases) are used plus the 380 discontinuous bases of segment 6 derived from deep sequencing. C/Lancaster/1/2015 is less divergent from the root than it should be given its known sampling date, consistent with a perturbation of molecular clock-like behaviour in its lineage.

Figure 4. Neighbour joining tree rooted on C/Taylor/1233/1947 for segment 5 (NP), annotated with clades as previously derived, demonstrating the closer relationship of C/Lancaster/1/2015 (red) to NP segments of the C/Miyagi/1/93 clade than to recent isolates.

Scale: substitutions per site.

Figure 5. Neighbour joining tree rooted on C/Taylor/1233/1947 for segment 7 (NS1/NS2), annotated with clades as previously derived, demonstrating the closer relationship of C/Lancaster/1/2015 (red) to NS1/NS2 segments of the C/Sapporo/71 clade from the 1970s than to recent isolates.

Scale: substitutions per site.