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Everything about Influenza Type D

The public understanding of influenza is often inadequate and narrowed down mainly to flu spread among humans and its peak during cold seasons. Influenza A and B viruses hold the stage for human influenza infections as the chief roots of seasonal and local epidemics, with various subtypes. However, other animal species are also in jeopardy of respiratory infections via influenza viruses. Influenza D virus (IDV) circulates among agricultural animals, specifically cattle and swine. It was detected by origin in U.S. Oklahoma in 2011 as an isolated virus in pigs. From there on, a series of surveillance began to gather information on influenza type D. Studies showed a percentage of pigs, along with horses, camelids, goats, wild boars, and sheep, had antibodies for the influenza D virus. Besides, the findings approved virus is inclined to afflict cattle more frequently, regardless of its origins in the swine population. Read on to learn more about influenza D, its host range, and how it relates to humans.


The Construction of Influenza D Virus

Before 2011, the influenza D virus was counted as a subtype of the influenza C virus. That can be evidently understood in the 50% homology between the two as they share a half similarity in amino acid composition. In line with the other influenza types, the influenza D virus is a single-stranded, negative-sense RNA virus associated with the family Orthomyxoviridae. Besides the nucleoprotein (NP) and matrix protein (M1), all viruses of this family also comprise glycoproteins or molecules that contain protein and carbohydrate chains on the surface. The relatively more expanding types, influenza A and B, possess two glycoproteins. In contrast, the other two hold one glycoprotein designated hemagglutinin-esterase fusion or HEF. Though at different rates, these glycoproteins can mutate and bring about antigenic drifts or shifts. As an offshoot of the influenza C virus, IDV similarly encodes 9 proteins with 7 RNA segments and can only undergo antigenic drifts. Consequently, various subtypes of influenza D have come to exist.


Different Lineages of Influenza D

On the whole, there are four lineages of influenza D viruses going around, mainly among pigs and bovines, without being restricted to specific regions. The first two include D/660 (D/bovine/Oklahoma/660/2013) and D/OK (D/swine/Oklahoma/1334/2011), which, as the full names suggest, were introduced not so long after IDV was isolated. On top of that, two more lineages, namely D/Yama2016 and D/Yama2019, have been recognized in the whereabouts of Japan and mainly among cattle herds. Each of these lineages has dissimilarities with respect to the hemagglutinin-esterase segments, and a total of 65 HEF nucleotide sequences exist. In spite of the bovine and pig populations as the primary targets, different influenza D viruses are capable of spillage to other animal species, such as horses, sheep, goats, and even poultry, which makes them an underlying threat to animal health on a global scale.


The distinction and Host Range

Some studies traced back the influenza D virus in a few archived samples from around 2003, though it became distinctively known as a different type of influenza in 2011. As mentioned, influenza D is primarily maintained in cattle as the primary reservoir host. This is while wild aquatic birds and shorebirds are considered the natural reservoir for influenza A, and types B and C have no determined animal reservoir. The host range of influenza D, however, encompasses more species, as pertinent antibodies have been detected in goats, dromedary camels, sheep, Asian buffalo, horses, and wild boar. It is yet to be approved if poultry is at risk of infection due to contradictory results from different studies. Yet, guinea pigs, mice, and ferrets have shown susceptibility to experimental infections.


Influenza D Virus and Humans

The primary interaction of humans with influenza concerns influenza A and influenza B. The former, being the most contagious type, comprises various subtypes that co-circulate around the globe and mutate rapidly. They are also responsible for seasonal flu. That being said, the influenza D virus is structurally similar to the influenza C virus. Thus, it is possible for humans to be prone to infection with influenza D, especially people in contact with livestock. According to several serological studies on seroprevalence (the amount of the IDV pathogen in blood serum) in farmers and, in some cases, non-cattle-exposed individuals, antibodies against the influenza D virus have been observed. Although no human infection with influenza D has been reported, it remains a potential threat to public health. For example, people can carry influenza D nucleic acid within their nasal passages, as observed in one worker on an Asian swine farm; it may not be human-threatening (at least for now) but can be a way of transmission to animals.


Transmission Routes, Signs, and Prevention

Influenza is generally taken to be transmitted via bodily liquids and secretions through direct contact, and influenza type D is not a different kettle of fish. Some also claim the possible transmissibility of influenza D viruses through the intestinal tract. Influenza D may cause some clinical signs depending on the animal species and the animal’s overall health status. For instance, calves may undergo upper respiratory symptoms like dry cough, wheezing, and nasal discharge, while others might suffer from mild fever and microscopic lesions. Moreover, influenza D can take it up in terms of severity and feed into further secondary bacterial infections. This may lead to bovine respiratory disease complex (BRDC), also called pneumonia or shipping fever, as more than 21% of cattle in the U.S. are affected. Some factors like animal immunity, age, and environment are involved, and antibiotics might work effectively in order to stop the disease from stepping into such devastating stages. Nevertheless, there are no specific treatments for influenza D in general. Because of that, it is crucial to comply with prevention guidelines. Aside from maintaining herds in good health, keeping the infected ones in quarantine is pivotal to cease the spread.


Vaccination for Influenza type D

As for influenza C, the available human vaccines do not immunize against influenza D viruses. The reason is the infrequency of type C in general and the vague association of type D influenza to human infections. Nevertheless, the growing prevalence of influenza D among cattle is too critical to be overlooked. This is highly important as it plays a significant role in preventing further spread and mutations which can make way for later zoonotic diseases and bring about economic damages. Two vaccines for influenza D can currently be utilized for cattle: DNA vaccines and inactivated virus vaccines. The former is considered more efficient as it provides protection against the two main lineages of influenza D viruses. In contrast, the inactivated influenza D vaccine partially protects against the virus.


Final Thoughts

As a newly introduced disease in agricultural animals, influenza type D is the least known type of influenza, isolated initially in 2011 from an infected swine. Influenza D is considered cosmopolitan as multiple studies show traces of antibodies in various geographic regions, such as Asia, North America, and Africa. Though studies have depicted many other species with IDV-specific antibodies, like horses, wild boar, and sheep, it holds cattle as its main animal reservoir. In contrast, no clear link between influenza D and humans has been approved. Nonetheless, the influenza D virus’s course of evolution has come down to four distinct lineages, which signifies the potential risk of epidemic infections in the future. In the absence of exclusive treatments, the optimal way to deal with influenza D is vaccination for cattle. Currently, two vaccines are available, namely the DNA and the inactivated virus vaccines.

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