Influenza D virus: a potential threat for humans?

Abstract

Abstract Influenza D virus (IDV) is a novel influenza virus, first isolated from an ailing swine in 2011 in Oklahoma. Several studies have isolated IDV in cattle from multiple geographic areas, suggesting cattle as a possible primary natural reservoir for the virus. To date, few studies have been performed on human samples and there is no conclusive evidence on the ability of the virus to infect humans. This serological study aimed to assess the IDV prevalence in archived human serum samples collected in Italy from 2005 to 2017. The serum samples were tested by haemagglutination inhibition assay (HI) and confirmed by the virus neutralization assay. The results clearly show that specific HI antibodies against IDV were present in at least a small subset of serum samples taken in every single year between 2005 and 2017, although IDV was isolated and described for the first time in 2011. IDV antibodies displayed low levels, between 5.1% and 9.8%, in the years 2005 to 2007, followed by a sharp increase in 2008; the highest levels (33.9% - 46.0%) were reached in 2008, 2009, 2010, 2013, 2014 and 2016, while the lowest levels (11.9% - 25.7%) were seen in 2011, 2012, 2015 and 2017. In addition, the highest levels of HI seropositivity (HI titers ≥ 1:40) were found in serum samples collected in 2008, 2009, 2012, 2013, 2014 and 2016. This increase was not constant over the years, it shows sharp rises in some years followed by drops in subsequent years. The seroprevalence peaks detected in humans appear to follow IDV epidemics in animals. Moreover, as the titers did not remain high in the years following the increase, but dropped to lower levels, it is likely that a spill over event from an animal reservoir occurred, and that the virus does not circulate primarily in humans. Ultimately, the virus showed the ability to infect and elicit an immune response in humans and not to persist in the human population. Key messages Current knowledge of influenza D virus in humans is still limited. Neither potential threats to exposed individuals nor public health issues can be fully excluded.