Canarypox Virus
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Canarypox virus (CNPV) is an ''
Avipoxvirus ''Avipoxvirus'' (avian pox) is a genus of viruses within the family ''Poxviridae''. ''Poxviridae'' is the family of viruses which cause the afflicted organism to have poxes as a symptom. Poxviruses have generally large genomes, and other such ex ...
'' and etiologic agent of canarypox, a disease of wild and captive birds that can cause significant losses. Canarypox can enter human cells, but it cannot survive and multiply in human cells. There is a live viral vaccine available which may have beneficial properties against human cancer when used as a mammalian expression vector. (
ATCvet The Anatomical Therapeutic Chemical (ATC) Classification System is a drug classification system that classifies the active ingredients of drugs according to the organ or system on which they act and their therapeutic, pharmacological and chemical ...
code: ). Furthermore, the POXIMUNE® C vaccine does offer direct protection against CNPV in susceptible birds. Generally CNPV is considered a disease of
songbird A songbird is a bird belonging to the suborder Passeri of the perching birds (Passeriformes). Another name that is sometimes seen as the scientific or vernacular name is Oscines, from Latin ''oscen'', "songbird". The Passeriformes contains 5000 ...
s, such as canaries,
magpie Magpies are birds of the Corvidae family. Like other members of their family, they are widely considered to be intelligent creatures. The Eurasian magpie, for instance, is thought to rank among the world's most intelligent creatures, and is one ...
s and
nightingale The common nightingale, rufous nightingale or simply nightingale (''Luscinia megarhynchos''), is a small passerine bird best known for its powerful and beautiful song. It was formerly classed as a member of the thrush family Turdidae, but is no ...
s, and is associated with higher mortality rates when compared to other avian pox viruses. In some instances, mortality approaches 100%. Avian pox viruses also cause significant economic losses in domestic
poultry Poultry () are domesticated birds kept by humans for their eggs, their meat or their feathers. These birds are most typically members of the superorder Galloanserae (fowl), especially the order Galliformes (which includes chickens, quails, a ...
and remain a problem in the conservation of endemic bird species inhabiting islands. The general symptoms of CNPV are similar to those of other species of avian pox viruses and are characterised by pustules and
diphtheria Diphtheria is an infection caused by the bacterium '' Corynebacterium diphtheriae''. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks more than 10% of those diagnosed with the disease may die. Signs and s ...
or
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...
-like symptoms.


Classification

Canarypox virus (CNPV) is a member of the ''Poxviridae'' family. Canarypox viruses, as with other bird pox viruses, are in the genera of ''Avipoxvirus''. Nine other species are also in the genus '' Avipoxvirus.'' These include:
Fowlpox Fowlpox is the worldwide disease of poultry caused by viruses of the family ''Poxviridae'' and the genus ''Avipoxvirus''. The viruses causing fowlpox are distinct from one another but antigenically similar, possible hosts including chickens, tur ...
virus, Juncopox virus, Mynahpox virus, Psittacinepox virus, Sparrowpox virus, Starlingpox virus,
Pigeonpox Pigeon pox is a viral disease to which only pigeons are susceptible. It is characterized by pox scabs, which most frequently form on the featherless parts of the bird. The disease is caused by the Pigeon pox virus.  It can be transmitted by drop ...
virus,
Turkeypox ''Turkeypox virus'' is a virus of the family ''Poxviridae'' and the genus ''Avipoxvirus'' that causes turkeypox. It is one of the most common diseases in the wild turkey (''Meleagris gallopavo'') population. Turkeypox, like all avipoxviruses, is ...
virus and Quailpox virus. It has thus far been reported that around 232 bird
species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...
(from 23 disparate
orders Order, ORDER or Orders may refer to: * Categorization, the process in which ideas and objects are recognized, differentiated, and understood * Heterarchy, a system of organization wherein the elements have the potential to be ranked a number of d ...
) are affected by avian pox virus.


Structure and replication

CNPV is an
enveloped virus A viral envelope is the outermost layer of many types of viruses. It protects the genetic material in their life cycle when traveling between host cells. Not all viruses have envelopes. Numerous human pathogenic viruses in circulation are encase ...
. They can be enveloped by double (external enveloped virion- EEV) or single (intracellular mature virion – IMV) membranes. These membranes are acquired from the host cell's endoplasmic reticulum (ER) or
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
. CNPV and other
poxvirus ''Poxviridae'' is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. There are currently 83 species in this family, divided among 22 genera, which are divided into two subfamilies. Diseases associated wit ...
es are characterised by having exceptionally large physical dimensions, approximately 330 nm×280 nm×200 nm. The
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 ...
of CNPV is linear and is composed of dsDNA. The genome size is approximately 365kbp, and in total, 328
genes In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
have been found. The shape of all poxviruses resembles something of a 'rounded brick' and remains determined by the specific envelope around the virus. The process which further characterises the poxvirus family is that replication occurs in the
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
and utilises a specific virus-made structure for replication, the '
virosome A virosome is a drug or vaccine delivery mechanism consisting of unilamellar phospholipid membrane (either a mono- or bi-layer) vesicle incorporating virus derived proteins to allow the virosomes to fuse with target cells. Viruses are infectious ...
'. Furthermore,
gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
is divided into three phases: early, intermediate and late. At each stage specific genes and promoters are expressed. The structure and replication of CNPV also characterise other members of the ''Poxviridae'' family. The
vaccinia virus ''Vaccinia virus'' (VACV or VV) is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, which encodes approximately 250 genes. The dimensions of the ...
is commonly used as a prototype and can be consulted for further information.


Transmission

The most common form of spread of CNPV is by
vector Vector most often refers to: *Euclidean vector, a quantity with a magnitude and a direction *Vector (epidemiology), an agent that carries and transmits an infectious pathogen into another living organism Vector may also refer to: Mathematic ...
s such as
mosquitoes Mosquitoes (or mosquitos) are members of a group of almost 3,600 species of small flies within the family Culicidae (from the Latin ''culex'' meaning "gnat"). The word "mosquito" (formed by ''mosca'' and diminutive ''-ito'') is Spanish for "litt ...
and mites. These transmit the virus from infected birds to non-infected birds. Direct routes of transmission have also been observed, especially in closed environments such as
aviaries An aviary is a large enclosure for confining birds, although bats may also be considered for display. Unlike birdcages, aviaries allow birds a larger living space where they can fly; hence, aviaries are also sometimes known as flight cages. Avi ...
or
farms A farm (also called an agricultural holding) is an area of land that is devoted primarily to agricultural processes with the primary objective of producing food and other crops; it is the basic facility in food production. The name is used fo ...
, where the contact rate of birds is high. When the virus is transmitted directly, this would usually occur through aerosols, consumption of infected bird tissue or by general contact with the diseased bird. Healthy birds are at increased risk of acquiring the disease through existing wounds or scabs when in close contact with diseased birds. The typical
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 ...
for the virus is between 5–10 days.


Symptoms

CNPV symptoms often show two main forms. That is either dry (
cutaneous Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different d ...
) and/or wet (diphtheritic) symptoms (both forms can occur at the same time). The dry form is the most frequently observed. At the beginning of the disease, small white/yellow
blister A blister is a small pocket of body fluid (lymph, serum, plasma, blood, or pus) within the upper layers of the skin, usually caused by forceful rubbing (friction), burning, freezing, chemical exposure or infection. Most blisters are filled wi ...
s form on the uncovered parts of the skin. As the disease progresses blisters get progressively larger and form nodules where the virus can multiply. When the nodules coalesce and burst, scabs are formed leaving rough, dry and pigmented areas on the skin where the nodules were. This form of the disease is usually mild and does not cause death. The chances of mortality increase when the dry form occurs together with the wet (diphtheritic) form. The wet form symptoms include an enlarged
thymus The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. ...
and obstructed
lungs The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of th ...
,
sinuses Paranasal sinuses are a group of four paired air-filled spaces that surround the nasal cavity. The maxillary sinuses are located under the eyes; the frontal sinuses are above the eyes; the ethmoidal sinuses are between the eyes and the sphenoid ...
and
trachea The trachea, also known as the windpipe, is a Cartilage, cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all air-breathing animals with lungs. The trachea extends ...
with white areas of
necrotic tissue Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated diges ...
. This results in restricted air intake and the potential for suffocation. It has also been observed that some birds may also experience thickened eyelids, air-sacks and enlarged spleens. Observations under the
microscope A microscope () is a laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic means being invisibl ...
have shown that the lesions are characterised by epithelial proliferation and
hypertrophy Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number.Updated by Linda J ...
in the viral infected areas. Characteristics of avian pox include the formation of intracytoplasmic inclusion bodies (' Bollinger bodies') which are composed of mononuclear inflammatory cells and have been detected in the
thymus The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. ...
,
spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .
,
bone marrow Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...
,
middle ear The middle ear is the portion of the ear medial to the eardrum, and distal to the oval window of the cochlea (of the inner ear). The mammalian middle ear contains three ossicles, which transfer the vibrations of the eardrum into waves in the ...
and
air sac Air sacs are spaces within an organism where there is the constant presence of air. Among modern animals, birds possess the most air sacs (9–11), with their extinct dinosaurian relatives showing a great increase in the pneumatization (presence ...
. Similar inclusion bodies which are associated with
inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
have also been seen in the
epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water rele ...
, feather follicles, sinuses and oral mucosa lining. Apart from the symptoms mentioned above, more general signs of infection include weight loss, loss of feathers and scaly skin on the head, neck and back. Secondary bacterial infections are common with both forms of the disease, having the potential to cause
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...
or other bacterial infections at the sites of
blister A blister is a small pocket of body fluid (lymph, serum, plasma, blood, or pus) within the upper layers of the skin, usually caused by forceful rubbing (friction), burning, freezing, chemical exposure or infection. Most blisters are filled wi ...
ing.


Treatment

Currently there is no treatment available. Diseased birds should however be admitted to a veterinary practice where suitable care will be provided. Care would normally consist of removing skin from the
lesions A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...
and washing the infected area(s) with
Lugol's iodine Lugol's iodine, also known as aqueous iodine and strong iodine solution, is a solution of potassium iodide with iodine in water. It is a medication and disinfectant used for a number of purposes. Taken by mouth it is used to treat thyrotoxicos ...
solution. Furthermore, swabbing of the mouth and
throat In vertebrate anatomy, the throat is the front part of the neck, internally positioned in front of the vertebrae. It contains the pharynx and larynx. An important section of it is the epiglottis, separating the esophagus from the trachea (windpipe ...
areas to remove
necrotic tissue Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated diges ...
s is common. By keeping diseased birds in warmer temperatures and ensuring daily eye rinsing with 1-2%
saline solution Saline (also known as saline solution) is a mixture of sodium chloride (salt) and water. It has a number of uses in medicine including cleaning wounds, removal and storage of contact lenses, and help with dry eyes. By injection into a vein i ...
has also been shown to promote recovery. In some cases, the infected birds are prescribed
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
. This will not target the virus but its use is designed to prevent secondary
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
l and
fungal A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from th ...
infections which are often found in skin
lesions A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...
.


Medical


Avian prevention

A live attenuated CNPV
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
has been developed and is the best preventive measure against canarypox for captive grown canary birds and other
passerine A passerine () is any bird of the order Passeriformes (; from Latin 'sparrow' and '-shaped'), which includes more than half of all bird species. Sometimes known as perching birds, passerines are distinguished from other orders of birds by t ...
birds. The brand name 'Poximune® C' by Ceva is a freeze-dried vaccine, administered by the 'wing web' method to healthy, susceptible
passerine A passerine () is any bird of the order Passeriformes (; from Latin 'sparrow' and '-shaped'), which includes more than half of all bird species. Sometimes known as perching birds, passerines are distinguished from other orders of birds by t ...
birds who have reached at least four weeks of age. Booster vaccination is recommended every 6–12 months if the risk of disease remains high. Pox lesion formation around the vaccination area is indicative that the vaccine has been effective. The vaccine should not be administered during egg production or in the 4 weeks prior to this. In a Hawaiian study Poximune® provided treatment in some birds, with their symptoms lasting only a few weeks, others developed necrosis and some died or had symptoms for two months, and some birds needed another vaccine as the first vaccine did not work. Therefore, a range of symptoms can be observed in a clinical setting, while giving unambiguous results.


Mammalian medicine

CNPV has been used recently as a mammalian
expression vector An expression vector, otherwise known as an expression construct, is usually a plasmid or virus designed for gene expression in cells. The vector is used to introduce a specific gene into a target cell, and can commandeer the cell's mechanism for ...
in the vaccine industry. The expression system using CNPV is advantageous because it undergoes what is known as ‘abortive infection’ but at the same time displays the necessary antigens to the hosts
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
. Although veterinary CNPV recombinant vaccines exist, recent attention has focussed on its use in human medicine with several human vaccines using this expression system undergoing
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
s. The vaccines typically use the CNPV ALVAC strain, which is highly attenuated. The use of this strain has been involved in the expression of several key
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
and tumour associated antigens. These include (but are not limited to) those found in
rabies virus Rabies virus, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lys ...
,
hepatitis B Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. Fo ...
and
hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...
, leukaemia virus,
HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
and
cancers Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
; such as
melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
and
colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...
s. A strain of canarypox virus modified to carry feline
interleukin-2 Interleukin-2 (IL-2) is an interleukin, a type of cytokine signaling molecule in the immune system. It is a 15.5–16  kDa protein that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible fo ...
called vCP1338 is used to treat cats with
fibrosarcoma Fibrosarcoma (fibroblastic sarcoma) is a malignant mesenchymal tumour derived from fibrous connective tissue and characterized by the presence of immature proliferating fibroblasts or undifferentiated anaplastic spindle cells in a storiform pat ...
. More information can be found in an review by Weli et al, 2011.


Threats

Canarypox virus remains a constant threat to wild birds. Those most vulnerable are
passerine A passerine () is any bird of the order Passeriformes (; from Latin 'sparrow' and '-shaped'), which includes more than half of all bird species. Sometimes known as perching birds, passerines are distinguished from other orders of birds by t ...
birds, endemic on islands such as
Hawaii Hawaii ( ; haw, Hawaii or ) is a state in the Western United States, located in the Pacific Ocean about from the U.S. mainland. It is the only U.S. state outside North America, the only state that is an archipelago, and the only stat ...
and the Galapagos. Here they have experienced dramatic losses in bird numbers. Many more have become classified as
endangered species An endangered species is a species that is very likely to become extinct in the near future, either worldwide or in a particular political jurisdiction. Endangered species may be at risk due to factors such as habitat loss, poaching and inv ...
due to CNPV. The disease is mainly spread by mosquitoes and mites in these regions, which were introduced during European colonisation. Canarypox, together with
avian malaria Avian malaria is a parasitic disease of birds, caused by parasite species belonging to the genera '' Plasmodium'' and '' Hemoproteus'' (phylum Apicomplexa, class Haemosporidia, family Plasmoiidae). The disease is transmitted by a dipteran vecto ...
, are the most devastating diseases for birds on the island of
Hawaii Hawaii ( ; haw, Hawaii or ) is a state in the Western United States, located in the Pacific Ocean about from the U.S. mainland. It is the only U.S. state outside North America, the only state that is an archipelago, and the only stat ...
and surrounding regions.


References

{{Taxonbar, from=Q2936179 Chordopoxvirinae Bird diseases Animal viral diseases