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Viruses: Influenza D in Domestic and Wild Animals

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  • Viruses: Influenza D in Domestic and Wild Animals

    Viruses: Influenza D in Domestic and Wild Animals


    When we discuss human influenza viruses, Influenza A and Influenza B pretty much dominate the field. Less well known are Influenza C viruses and Influenza D viruses, both of which can occur in swine and cattle, but appear to have limited abilities to infect humans.

    The CDC describes these outlier flu viruses as:

    Influenza C virus infections generally cause mild illness and are not thought to cause human epidemics. Influenza D viruses primarily affect cattle and are not known to infect or cause illness in people.

    But the caveat is, we routinely only test for Influenza A & B viruses. Very rarely do we test for Influenza C & D. Which means our understanding of their spread and impact in humans is quite limited.

    In recent years we've looked at a number of studies which suggest that Influenza C may be less benign that previously thought.Although we've known about influenza C since the late 1940s, Influenza D was only first discovered in 2011 (see PLoS Pathogens: A New Influenza C Virus Detected In Swine), but was later reclassified as influenza D.

    Since then, researchers have found evidence of a much wider spread of this virus (now officially called Influenza D) than just in the American Midwest. (see EID journal’s Influenza D Virus in Cattle, France, 2011–2014 and EID Journal: Influenza D In Cattle & Swine – Italy).

    While it isn't known if Influenza D can cause symptomatic illness in humans, in the summer of 2016 - in Serological Evidence Of Influenza D Among Persons With & Without Cattle Exposure - researchers reported finding a high prevalence of antibodies against Influenza D among people with cattle exposure. They wrote:

    IDV poses a zoonotic risk to cattle-exposed workers, based on detection of high seroprevalence (94–97%). Whereas it is still unknown whether IDV causes disease in humans, our studies indicate that the virus may be an emerging pathogen among cattle-workers.

    We've revisited Influenza D a number of times since then, including 2019's J. Clinical Med. : A Review Of The Emerging Influenza D Virus, and 2022's Zoonoses & Pub. Health: Influenza D Virus Exposure Among US Cattle Workers: A Call for Surveillance.

    All of which brings us to a new review - published last week in the Journal Viruses - which once again warns of influenza D's extended host range and zoonotic potential.

    Due to its length, I've only posted some excerpts below. Follow the link to read the review in its entirety. I'll have a brief postscript when you return.


    Influenza D virus (IDV) infections have been observed in animals worldwide, confirmed through both serological and molecular tests, as well as virus isolation. IDV possesses unique properties that distinguish it from other influenza viruses, primarily attributed to the hemagglutinin-esterase fusion (HEF) surface glycoprotein, which determines the virus’ tropism and wide host range. Cattle are postulated to be the reservoir of IDV, and the virus is identified as one of the causative agents of bovine respiratory disease (BRD) syndrome.
    Animals associated with humans and susceptible to IDV infection include camels, pigs, small ruminants, and horses. Notably, high seroprevalence towards IDV, apart from cattle, is also observed in camels, potentially constituting a reservoir of the virus. Among wild and captive animals, IDV infections have been confirmed in feral pigs, wild boars, deer, hedgehogs, giraffes, wildebeests, kangaroos, wallabies, and llamas. The transmission potential and host range of IDV may contribute to future viral differentiation. It has been confirmed that influenza D may pose a threat to humans as a zoonosis, with seroprevalence noted in people with professional contact with cattle.

    1. Introduction

    Influenza D virus (IDV) belongs to the Orthomyxoviridae family, the genus Deltainfluenzavirus, along with influenza viruses of the genera Alphainfluenzavirus (Influenzavirus A, IAV), Betainfluenzavirus (Influenzavirus B, IBV), and Gammainfluenzavirus (Influenzavirus C, ICV). Influenza viruses of distinct types (A, B, C, or D) exhibit variations in genome structure, properties of surface glycoproteins, and the antigenicity of the viral nucleoprotein and matrix protein [
    1,2]. Influenza viruses belonging to different types also display differing host ranges.

    Influenza A viruses exhibit broad host tropism, can infect wildfowl, swine, horses, bats, and humans, leading to severe respiratory disease and seasonal epidemics, and have the potential for triggering pandemics [
    3]. Based on the surface glycoproteins hemagglutinin and neuraminidase, IAV is divided into subtypes (H1 to H18 and N1 to N11). The main hosts for IBV and ICV are humans, IBV may cause seasonal epidemics, while ICV causes only mild illness. IBV has been isolated from seals and pigs [4,5]; antibodies against IBV were also reported in dogs and horses [6,7]. ICV can occasionally infect cattle [8], dogs, and pigs [9,10]. Serological evidence of ICV was reported also in equine populations [11].

    Influenza D virus is a relatively recent discovery, first identified in 2011 in pigs in the USA, although evidence indicates its circulation in cattle populations since at least 2003 [
    2,12]. IDV’s global distribution is now well-established, with reports from Europe, North America, South America, Africa, Asia, and recently Australia [13,14,15,16,17,18] (Figure 1).


    This review provides information on the occurrence of influenza D infections in numerous domestic and wild animal species. Due to its relatively recent discovery, IDV is the least investigated among the influenza viruses. Therefore, we have introduced basic information on the structure of the virion, phylogenetic analysis of circulating strains, disease symptoms, and diagnostic methods.


    6. Zoonotic Potential of IDV

    The study of human sera in the USA and Canada in 2011 showed an IDV seroprevalence of 1.3%, while a study in Italy showed a seroprevalence ranging from 5.1% in 2005 to 46% in 2014 [21,104]. Leible et al. assessed IDV exposure among thirty-one workers on five large dairy farms; the presence of IDV was found in the nasal washes of 67% of people at least once during the 5-day study period. However, IDV presence was not associated with respiratory symptoms in these workers [27]. Despite serological studies, there is no direct evidence that IDV can infect humans, and no infections in humans have been reported to date. Studies on the properties of IDV receptors [105], the virus replication capacity in a model of human respiratory epithelium [103], as well as the detection of viral genetic material in airport bioaerosol [106], in a hospital [107], and in a pig farmer’s nasal swabs [108] suggest that humans may be susceptible to infection.

    7. Conclusions

    The influenza D virus is unique among other influenza viruses in terms of virion properties as well as host range and reservoir. As with influenza A viruses, a wide host range gives IDV a particular opportunity to reassort, mutate, and promote viral diversity. In most European countries where IDV seroprevalence studies were conducted in cattle, the results indicate several dozen percent of positive animals, and an equally high seroprevalence rate is recorded in some parts of Asia and the USA. Cattle may play an important role in the spread of IDV around the world, including being a source of infection for other farm animals, wild animals, and humans. It should be noted that high seroprevalence is observed also in camels, which may constitute a reservoir of IDV in tropical regions. However, the level of seroprevalence against IDV is much lower in pigs, small ruminants, and horses compared to cattle.

    Among wild animals, the most extensive research has been conducted on feral swine in the USA and various species of deer in both the USA and Europe. The results confirmed the presence of antibodies against IDV in these animals. Given the abundance of both feral swine in the USA and deer in Europe, these groups may be important in the ecology of the virus. Molecular or serological tests confirmed the occurrence of IDV infection in different animal species: giraffes, kangaroos, wildebeests, wallabies, llamas, and hedgehogs.

    It is assumed that influenza D may pose a threat as a zoonotic disease, and seroprevalence was confirmed in people with professional contact with cattle. It seems important to monitor the occurrence of IDV not only in domestic animals but also in wild animals, which may act as natural reservoirs. The infectivity and cross-species transmission capacity of IDV make the virus an increasing epidemiological threat, requiring surveillance and further research.

    The overriding theme of this blog over the past 17+ years has been that Nature's laboratory is open 24/7 - and that it operates without budgetary constraints, ethical considerations, or human oversight - and that it is continually creating or modifying an untold number of viruses, bacteria, and fungi.

    Most of these pathogens will never rise to the level of a public health threat, but it's a numbers game. Given the number of players, over time the odds greatly favor the emergence of another novel pandemic threat.

    Influenza A remains our biggest pandemic concern, but it is always possible that a mutated influenza C or D virus could someday become a contender. After all, twenty-five years ago few would have bet on a novel coronavirus sparking a severe pandemic.

    Which is why - long shot or not - influenza C and influenza D are deserving of more study.

      #17,824 When we discuss human influenza viruses, Influenza A and Influenza B pretty much dominate the field. Less well known are Influen...
    All medical discussions are for educational purposes. I am not a doctor, just a retired paramedic. Nothing I post should be construed as specific medical advice. If you have a medical problem, see your physician.