Epidemiological and Virological Characterization of Influenza B Virus Infections

Abstract

While influenza A viruses comprise a heterogeneous group of clinically relevant influenza viruses, influenza B viruses form a more homogeneous cluster, divided mainly into two lineages: Victoria and Yamagata. This divergence has complicated seasonal influenza vaccine design, which traditionally contained two seasonal influenza A virus strains and one influenza B virus strain. We examined the distribution of the two influenza B virus lineages in Israel, between 2011-2014, in hospitalized and in non-hospitalized (community) influenza B virus-infected patients. We showed that influenza B virus infections can lead to hospitalization and demonstrated that during some winter seasons, both influenza B virus lineages circulated simultaneously in Israel. We further show that the influenza B virus Yamagata lineage was dominant, circulating in the county in the last few years of the study period, consistent with the anti-Yamagata influenza B virus antibodies detected in the serum samples of affected individuals residing in Israel in the year 2014. Interestingly, we found that elderly people were particularly vulnerable to Yamagata lineage influenza B virus infections.

Fig 1. Infections with influenza viruses in Israel between 2011–2014.

The percent of hospitalized (A) and community (B) patients infected with influenza A(H3N2), B and A(H1N1)pdm viruses between 2011–2014. *p<0.05.

Fig 2. Infections with influenza B viruses in Israel between 2011–2014.

The monthly percent distribution of hospitalized (A) and community (B) patients positive for infection of influenza B viruses: Victoria and Yamagata between 2011–2014.

Fig 3. Temporal of influenza B infection.

The percentages of hospitalized (A) and community (B) patients, during the winter seasons of 2011–2014. *p<0.05.

Fig 4. Age distribution of the influenza B-infected patients.

The yearly age distribution of hospitalized (A) and community (B) patients positive for infection of influenza B viruses: Victoria and Yamagata between 2011–2014. Summary of the ages over the years in shown in (C-D).

Fig 5. Gender distribution in hospitalized patients.

The gender distribution of hospitalized Victoria-infected (A) and Yamagata-infected (B) patients between 2011–2014.

Fig 6. Antibodies against Yamagata were dominant in 2014.

Sera were collected from randomly selected individuals and the presence of antibodies against Victoria and Yamagata was detected as described in materials in methods. Summary of positive samples is shown in (A). Shown in (B) is the virus titers and in (C) Geometric Mean Titers (GMT) antibody neutralization of the Israeli circulating influenza B. (D) Microneutralization assays.

Fig 7. Phylogenetic tree.

Bayesian maximum-clade-credibility time-scaled phylogenetic tree (BEAST) generated using 74 partially sequenced influenza B HA gene (476 bp), obtained from patient samples collected between 2012 and 2014 in Israel.