Influenza D Virus

Influenza A and Influenza B have the potential to cause pandemics. Influenza C circulates together with Influenza A and B viruses during winter months. Influenza C ‘only’ causes upper and (far less frequently) lower respiratory tract infections in humans with relatively mild symptoms like fever, cough, runny nose and fatigue. Consequently, not a lot of research is done on this particular virus. Influenza C viruses are known to infect both human, pigs and dogs. Nearly all adults have, at one time in their life, been infected with Influenza C.

The effects of an infection with the Influenza C virus are perhaps only an inconvenience if you are a healthy adult, but it can become life-threatening if it concerns infants, elderly and patients that are immunocompromized, like patients that undergo chemotherapy.

The Influenza C virus behaves rather well and exhibits no antigenic shift but does have an antigenic drift[1], which means that the virus changes ever so slightly each new season. Thus, Influenza C has only one subtype.

Researchers[2] have tested all available Influenza C viruses and found that they could calculate that their most recent common ancestor appeared around 1890. That means that all known Influenza C viruses can trace their ancestry back to one that lived at the end of the nineteenth century.

One virus that is only slightly changing each and every year. This sounds all very reassuring.

Then news suddenly appeared in 2013 that a novel virus had been discovered that was distantly related to the Influenza C virus. In April 2011, nasal swabs were collected from pigs in the state of Olkahoma in the US that were exhibiting influenza-like illness. Studies[3] identified a virus exhibiting approximately 50% overall identity to Influenza C virus. Based on its similarities to influenza C viruses this virus was at first designated as C/Oklahoma/1334/2011 (C/OK). Further research demonstrated that C/OK virus is genetically and antigenically so distinct from existing circulating Influenza C Viruses, that the scientists proposed[4] that this novel virus should be classified as yet another separate genus within the Orthomyxoviridae family and should be named Influenza D Virus: D/OK/2013

In 2014 news arrived that French scientists had found a related virus in cows: Influenza D/bovine/France/2986/2012 and D/bovine/France/2956/2012[5]. Then news from China appeared that claimed that the virus was also detected in Chinese cows[6].

A puzzling question raised by this studies is the geographic origin of these or Influenza D strains: were cattle in France and China contaminated by their North American counterparts or vice versa? Did co-evolution occur? Did the pathogen originate from a distinct location or from a distinct host?

Sheep and goats were also shown to be susceptible to Influenza D Virus and multiple states in the U.S. have this virus infection already discovered in these two species[7].

The presence of multiple subtypes of circulating influenza D viruses in multiple species raises the possibility of reassortment and antigenic shift as mechanisms of influenza D virus evolution. And if there's one, there are bound to be more.

[1] Gerth: Is there evidence for antigenic drift of influenza C viruses? in Zentralblatt für Bakteriologie, Parasitenkunde, Infektionskrankheiten und Hygiene - 1975
[2] Gatherer: Tempo and mode in the molecular evolution of influenza C in PLoS Currents – 2010
[3] Hause et al: Isolation of a novel swine influenza virus from Oklahoma in 2011 which is distantly related to human influenza C viruses in PLoS Pathogens 2013
[4] Hause et al: Characterization of a novel influenza virus in cattle and swine: proposal for a new genus in the orthomyxoviridae family in mBio - 2014
[5] Ducate et al: Influenza D Virus in Cattle, France, 2011–2014 in Emerging Infectious Diseases – 2015 
[6] Jiang et al:Identification of a potential novel type of influenza virus in Bovine in China in Virus Genes - 2014 
[7] Quast et al: [4] Quast et al: Serological evidence for the presence of influenza D virus in small ruminants in Veterinary Microbiology - 2015