Domestic pigs are susceptible to infection with influenza B viruses

Abstract

Influenza B virus (IBV) causes seasonal epidemics in humans. Although IBV has been isolated from seals, humans are considered the primary host and reservoir of this important pathogen. It is unclear whether other animal species can support the replication of IBV and serve as a reservoir. Swine are naturally infected with both influenza A and C viruses. To determine the susceptibility of pigs to IBV infection, we conducted a serological survey for U.S. Midwest domestic swine herds from 2010 to 2012. Results of this study showed that antibodies to IBVs were detected in 38.5% (20/52) of sampled farms, and 7.3% (41/560) of tested swine serum samples were positive for IBV antibodies. Furthermore, swine herds infected with porcine reproductive and respiratory syndrome virus (PRRSV) showed a higher prevalence of IBV antibodies in our 2014 survey. In addition, IBV was detected in 3 nasal swabs collected from PRRSV-seropositive pigs by real-time RT-PCR and sequencing. Finally, an experimental infection in pigs, via intranasal and intratracheal routes, was performed using one representative virus from each of the two genetically and antigenically distinct lineages of IBVs: B/Brisbane/60/2008 (Victoria lineage) and B/Yamagata/16/1988 (Yamagata lineage). Pigs developed influenza-like symptoms and lung lesions, and they seroconverted after virus inoculation. Pigs infected with B/Brisbane/60/2008 virus successfully transmitted the virus to sentinel animals. Taken together, our data demonstrate that pigs are susceptible to IBV infection; therefore, they warrant further surveillance and investigation of swine as a potential host for human IBV.

Importance: IBV is an important human pathogen, but its ability to infect other species, for example, pigs, is not well understood. We showed serological evidence that antibodies to two genetically and antigenically distinct lineages of IBVs were present among domestic pigs, especially in swine herds previously infected with PRRSV, an immunosuppressive virus. IBV was detected in 3 nasal swabs from PRRSV-seropositive pigs by real-time reverse transcription-PCR and sequencing. Moreover, both lineages of IBV were able to infect pigs under experimental conditions, with transmissibility of influenza B/Victoria lineage virus among pigs being observed. Our results demonstrate that pigs are susceptible to IBV infections, indicating that IBV is a swine pathogen, and swine may serve as a natural reservoir of IBVs. In addition, pigs may serve as a model to study the mechanisms of transmission and pathogenesis of IBVs.

FIG 1

Transmission of B/Brisbane/60/2008 virus from inoculated pigs to contact animals. Eight pigs were inoculated intratracheally and intranasally with influenza B/Brisbane/60/2008 virus at a dose of 3 × 10⁶ TCID₅₀/ml. Four contact pigs were comingled with the challenged pigs at 2 days postinfection (dpi) to investigate viral transmission. Six out of 8 inoculated pigs shed virus by nasal cavity, and 2 inoculated pigs did not shed virus. Nasal shedding was detectable in 1 out of 4 contact pigs. Solid lines represent inoculated pigs, while dotted lines are used to represent contact animals.

FIG 2

Microscopic lung sections from pigs infected with IBVs at 5 days postinfection (dpi). (A) Control pigs. The bronchioles are lined by normal cuboidal epithelium (arrow), and the alveoli are clear (star). (B and C) Infected pigs. Alveolitis is observed in pigs infected with either influenza B/Brisbane/60/2008 (B) or B/Yamagata/16/1988 (C) viruses. Multifocal areas of alveolitis are seen and are characterized by the presence of degenerate and intact neutrophils within the alveolar lumen (star), and there is a thickening of alveolar septa caused by inflammation. No bronchiolar epithelial necrosis is observed in any of the infected pigs. Bars, 50 μm.