''Influenza D virus '' is a species in the

virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...

genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In the hierarchy of biological classification, genus com ...

''Deltainfluenzavirus'', in the family ''

Orthomyxoviridae ''Orthomyxoviridae'' (from Greek language, Greek ὀρθός, ''orthós'' 'straight' + μύξα, ''mýxa'' 'mucus') is a family of negative-sense single-stranded RNA virus, negative-sense RNA viruses. It includes seven genus, genera: ''Influenza ...

'', that causes

influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...

. Influenza D viruses are known to infect

pig The pig (''Sus domesticus''), often called swine, hog, or domestic pig when distinguishing from other members of the genus '' Sus'', is an omnivorous, domesticated, even-toed, hoofed mammal. It is variously considered a subspecies of ''Sus ...

s and

cattle Cattle (''Bos taurus'') are large, domesticated, cloven-hooved, herbivores. They are a prominent modern member of the subfamily Bovinae and the most widespread species of the genus ''Bos''. Adult females are referred to as cows and adult mal ...

; no human infections from this virus have been observed. First isolated from pigs in 2011, the virus was categorized as a new genus of ''Orthomyxoviridae'' in 2016, distinct from the previously-known Influenzavirus C genus; before then, Influenza D virus was thought to be a subtype of Influenzavirus C. Cases of infections from the Type D virus are rare compared to Types A, B, and C. Similar to Type C, Type D has 7 RNA segments and encodes 9 proteins, while Types A and B have 8 RNA segments and encode at least 10 proteins.

Influenza D virus

The influenza viruses are members of the family ''

''. Influenza viruses A, B, C, and D represent the four

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

ic types of influenza viruses. Of the four antigenic types,

influenza A virus ''Influenza A virus'' (''IAV'') causes influenza in birds and some mammals, and is the only species of the genus ''Alphainfluenzavirus'' of the virus family ''Orthomyxoviridae''. Strain (biology)#Microbiology or virology, Strains of all subtypes ...

is the most severe,

influenza B virus ''Influenza B virus'' is the only species in the genus ''Betainfluenzavirus'' in the virus family ''Orthomyxoviridae''. Influenza B virus is known only to infect humans and seals. This limited host range is apparently responsible for the lack o ...

is less severe but can still cause outbreaks, and

influenza C virus ''Influenza C virus'' is the only species in the genus ''Gammainfluenzavirus'', in the virus family '' Orthomyxoviridae'', which like other influenza viruses, causes influenza. Influenza C viruses are known to infect humans and pigs. Flu due to ...

is usually only associated with minor symptoms. Influenzavirus D is less common than the other antigenic types, and it is not known to cause any human infections. No samples of influenza D virus were detected in serum samples from humans; however, hemagglutination-inhibiting antibodies against influenza D virus have been detected in humans, with an estimated occurrence of 1.3% in the general population, suggesting that this virus may infect humans as well. However, those antibodies may have been produced after an infection by influenza C virus, the antibodies for which cross-react with the Type D virus. More studies are needed to conclude whether or not the Type D virus can infect humans. Influenza D virus is 50% similar in amino acid composition to

, similar to the level of divergence between types A and B, while types C and D have a much greater level of divergence from types A and B. Influenzaviruses C and D were estimated to have diverged from a single ancestor over 1,500 years ago, around 482 AD. Influenzavirus D itself currently has two lineages, which were estimated to have emerged over 45 years ago, around 1972 AD. Influenza viruses A and B are estimated to have diverged from a single ancestor around 4,000 years ago, while the ancestor of influenza viruses A and B and the ancestor of influenza viruses C and D are estimated to have diverged from a common ancestor around 8,000 years ago. Metatranscriptomics studies have also identified closely related "Influenza C and D-like" viruses in a number of amphibian species. Influenza A virus can infect a variety of animals as well as humans, and its natural host or reservoir is birds, whereas influenza viruses B, C, and D do not have animal reservoirs. Influenza viruses C and D are not as easily isolated so less information is known about these types, but studies show that they occur worldwide. This virus may be spread through

respiratory droplet A respiratory droplet is a small aqueous droplet produced by exhalation, consisting of saliva or mucus and other matter derived from respiratory tract surfaces. Respiratory droplets are produced naturally as a result of breathing, speaking, snee ...

s or by

fomite A fomite () or fomes () is any inanimate object that, when contaminated with or exposed to infectious agents (such as pathogenic bacteria, viruses or fungi), can transfer disease to a new host. Transfer of pathogens by fomites A fomite is any ina ...

s (non-living material) due to its ability to survive on surfaces for short durations. Influenza viruses have a relatively short

incubation period Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or radiation, and when symptoms and signs are first apparent. In a typical infectious disease, the i ...

(lapse of time from exposure to pathogen to the appearance of symptoms) of 18–72 hours and infect the

epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...

of the

respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to th ...

. In cell culture, influenza D virus has demonstrated an ability to replicate well at 37°C, the normal lung temperature, and can also replicate better and in more types of cells than the Type C virus. This study suggests that influenza D virus may be only a few genetic changes away from being able to invade the lower lung, even though the virus does not actively spread among humans and has a much slower mutation rate than the other influenza viruses.

Structure and Variation

Influenza viruses, like all viruses in the family Orthomyxoviridae, are enveloped

RNA virus An RNA virus is a virusother than a retrovirusthat has ribonucleic acid (RNA) as its genetic material. The nucleic acid is usually single-stranded RNA ( ssRNA) but it may be double-stranded (dsRNA). Notable human diseases caused by RNA viruses ...

es with single stranded

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

s. The antigens, matrix protein (M1) and nucleoprotein (NP), are used to determine if an influenza virus is type A, B, C, or D. The M1 protein is required for virus assembly and NP functions in

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

and replication. These viruses also contain proteins on the surface of the cell membrane called glycoproteins. Type A and B have two glycoproteins: hemagglutinin (HA) and neuraminidase (NA). Types C and D have only one glycoprotein: hemagglutinin-esterase fusion (HEF). These glycoproteins allow for attachment and fusion of viral and cellular membranes. Fusion of these membranes allows the viral proteins and genome to be released into the host cell, which then causes the infection. Types C and D are the only influenza viruses to express the enzyme esterase. This enzyme is similar to the enzyme neuraminidase produced by Types A and B in that they both function in destroying the host cell receptors. Glycoproteins may undergo

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

s (antigenic drift) or reassortment in which a new HA or NA is produced (antigenic shift). Influenza viruses C and D are only capable of

antigenic drift Antigenic drift is a kind of genetic variation in viruses, arising from the accumulation of mutations in the virus genes that code for virus-surface proteins that host antibodies recognize. This results in a new strain of virus particles that is ...

whereas Type A undergoes

antigenic shift Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains. The term is ...

, as well. When either of these processes occur, the antibodies formed by the immune system no longer protect against these altered

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

s. Because of this, viruses continually cause infections.

Identification

Influenza viruses C and D are different from Types A and B in their growth requirements. Because of this, Influenzavirus D is not isolated and identified as frequently. Diagnosis is by virus isolation,

serology Serology is the scientific study of Serum (blood), serum and other body fluids. In practice, the term usually refers to the medical diagnosis, diagnostic identification of Antibody, antibodies in the serum. Such antibodies are typically formed in r ...

, and other tests. Hemagglutination inhibition (HI) is one method of serology that detects antibodies for diagnostic purposes.

Western blot The western blot (sometimes called the protein immunoblot), or western blotting, is a widely used analytical technique in molecular biology and immunogenetics to detect specific proteins in a sample of tissue homogenate or extract. Besides detect ...

(immunoblot assay) and enzyme-linked immunosorbent assay (

ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence ...

) are two other methods used to detect proteins (or antigens) in serum. In each of these techniques, the antibodies for the protein of interest are added and the presence of the specific protein is indicated by a color change. ELISA was shown to have higher sensitivity to the HEF than the HI test. Because only Influenza viruses C and D produce esterase, In Situ Esterase Assays provide a quick and inexpensive method of detecting just Types C and D.

Vaccination

Because influenza virus A has an animal reservoir that contains all the known subtypes and can undergo antigenic shift, this type of influenza virus is capable of producing

pandemic A pandemic () is an epidemic of an infectious disease that has spread across a large region, for instance multiple continents or worldwide, affecting a substantial number of individuals. A widespread endemic (epidemiology), endemic disease wi ...

s. Influenza viruses A and B also cause seasonal

epidemic An epidemic (from Ancient Greek, Greek ἐπί ''epi'' "upon or above" and δῆμος ''demos'' "people") is the rapid spread of disease to a large number of patients among a given population within an area in a short period of time. Epidemics ...

s every year due to their ability to antigenic shift. Influenza viruses C and D do not have this capability, and they have not been implicated in any pandemics; thus, there are currently no human vaccines available for Influenza viruses C or D. An inactivated Influenzavirus D vaccine was developed for cattle; however, the vaccine only provided partial protection in challenge experiments.

References

External links