Canine circovirus

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Canine circovirus
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Monodnaviria
Kingdom: Shotokuvirae
Phylum: Cressdnaviricota
Class: Arfiviricetes
Order: Cirlivirales
Family: Circoviridae
Genus: Circovirus
Species:
Canine circovirus

Canine circovirus (CaCV or DogCV), first isolated in 2012, is a small non-enveloped, icosahedral, single-stranded DNA virus that infects domestic dogs and wild canids exclusively. It is a member of the Circoviridae family and the genus Circovirus . There are currently 11 species of known circoviruses that have been identified to affect a wide variety of birds and mammals. As seen with all extensively studied circoviruses, the diameter ranges between approximately 15 and 25 nanometers. [1] The icosahedral triangulation number is 1, the smallest size a viral capsid can be, in which there are a total of 60 protein subunits that make up the capsid. CaCV is not to be confused with canine coronavirus, another diarrhea-causing agent within the family Coronaviridae, or porcine circoviruses which are a members of the same genus as CaCV but only seen in pigs. CaCV (genome 1) was the first Circovirus to be identified that infects a mammal species other than pigs.

Contents

Genome

The genome of CaCV is made up of a single circular strand of DNA 2,063 nucleotides in length. DNA in general is made up of four nitrogenous bases: adenine (A), thymine (T), cytosine (C), and guanine (G) in which A pairs with T and G pairs with C across complementary strands in double stranded DNA and occasionally in single stranded DNA with a specific sequence that promotes same-strand base pairing. CaCV exhibits this behavior in the form of stemloop structures. Guanine-Cytosine nucleotide base pairing makes up a little over half of the total pairs that are present in CaCV and the most abundant dinucleotides (when adjacent nucleotides on the same strand bind covalently to each other) observed are T-G and G-G. [2] The genome is made up of two coding and two noncoding sections. There are only two open reading frames (ORFs) that code for specific viral replicase and capsid proteins. Viral replicase proteins are made up of 303 amino acids and the viral capsid is constructed out of 270 amino acids. The gene coding for the capsid contains the sequence for 30 arginine amino acids originating from the amino terminus. This unusual stretch is hypothesized to be important for DNA binding. The two intergenic noncoding portions of the genome are made up of 135 and 203 nucleotides. These regions contain distinctive sequences for stemloop structures, in which the single stranded DNA pairs up and a ring is formed at the end, as well as segments of palindromes. There is one noncoding region between the two ORFs that contains a stemloop structure and the sequence TAGTATTAC used for the initiation of genome replication. The origin of replication site (ori) is located within the intergenic region between the two coding regions at the 5’ end. The palindromic sequences are an important feature there. An interesting note about the genome of CaCV is that one of the intergenic noncoding regions shares 91% nucleotide identity with the pine marten torque teno virus from the family Anelloviridae providing evidence of a possible evolutionary relationship between the two viruses.

Genome replication

A model of a general circovirus undergoing rolling circle replication, beginning with initiation at a particular nick site and ending at termination once the genome has been replicated in full. PCVmeltingpot.jpg
A model of a general circovirus undergoing rolling circle replication, beginning with initiation at a particular nick site and ending at termination once the genome has been replicated in full.

Rolling circle replication [3] is a method for replicating genomes that is seen most commonly in circular plasmids and genomes of bacteria and viruses. The important protein dimer that needs to be coded for in the DNA is the replication protein, Rep. Rep cleaves a location of the DNA exposing a free 3’ OH for viral or cellular polymerase to act on. DNA replication occurs in the nucleus of the cell in which this virus is small enough to enter into.

Symptoms

Circoviruses are generally known to be responsible for potentially fatal illnesses in birds, pigs, bats, dogs, minks, and humans. There is currently no literature on a potential vaccine against the virus for dogs, but there is one in effect for porcine circovirus. Symptoms of CaCV include hemorrhagic enteritis which is associated with sudden onset of weakened appetite, vomiting, and bloody diarrhea. Additionally, microscopic analysis has identified vasculitis, or inflammation of the blood vessels, and lymphphoid necrosis (failure) in affected animals. Organs that CaCV DNA has been shown to be present in include the intestines, spleen, lungs, brain, liver, and lymph nodes.

Co-infections are also a common occurrence in animals afflicted with CaCV. Canine distempter and parvovirus (genotype 2) were the most common co-infectors in a group of domestic dogs and other wild canids studied in 2016 by Zaccaria et al. [4] It is also suspected that younger individuals may be more at risk of developing life-threatening symptoms than adult animals, but that claim cannot yet be scientifically made due to sampling bias. A cure for CaCV is currently unknown and treatment is non-specific.

Case studies

In an article published in 2013 by Li et al. [5] a young (1 year) male domestic dog’s liver was analyzed for the presence of an infective agent. The dog was initially brought to the University of California, Davis Veterinary Medical Teaching Hospital because of increasing prevalence of vomiting, diarrhea, and blood in the stool (hematochezia). The dog was eventually euthanized and the owner agreed for postmortem tests to be run. Routine tests for more common infectious agents like parvovirus, coronavirus, and specific types of bacteria were negative. Hemorrhaging throughout the gastrointestinal tract and kidneys were shown along with other histological abnormalities. Liver tissue samples were taken and viral nucleic acids were sequenced which contained specific patterns characteristic of circovirus, giving evidence for CaCV to be the sole cause of death.

In the same paper, fecal matter of a cohort sample of dogs with and without diarrhea was analyzed using real-time PCR techniques to determine the percent prevalence of circovirus. There was not any significant difference between the identification of CaCV DNA in dogs with diarrhea compared to those without, however additional data were found to be interesting. Within the group of dogs that tested positive for CaCV, 68% of them had other co-infections of varying illnesses.

There have been other journal articles that have addressed an apparent relationship between CaCV and other co-infection agents. Thaiwong et al. [6] submitted a publication in 2016 on a dual infection incident of CaCV and canine parvovirus in a breeding colony of dogs. Two disease outbreaks occurred in Michigan in 2013 and 2014 in which a group of related Papillon dogs became ill and some died shortly (within 1 week) after symptoms began to show. The bodies of the dogs that died were accepted for necroscopy. The intestines, spleen, and lymph nodes were most affected with deformities such as segmental mucosal collapse, villar shortening, lymphoid necrosis, lymphocytolysis, multifocal granulomatous inflammation, and histiocytosis. These events led to overall organ failure and production of unusual mucus secretions. PCR analysis and sequencing of the treated organ tissues revealed large amounts of CaCV DNA and canine parvovirus-2 DNA and antigens.

Other studies have mentioned the presence of CaCV in other countries other than the United States. An additional article by Decaro et al. [7] highlights a breakout of enteritis disease in a litter of puppies in Southern Italy. Two dogs died within a week of infection while the others were ill but able to recover. One of the bodies underwent laboratory analysis and necroscopy to determine the infectious agent(s). By using RT-PCR techniques and sequencing, the liver and gut samples tested positive for the presence of the CaCV replicase gene. All other pathogens that were screened for came up negative. Prevalence of CaCV in Taiwan [8] was also studied in which dogs with diarrhea were approximately three times more likely to be infected with CaCV than healthy dogs. This contrasted the study run by Li et al. [9] in the US in which dogs with diarrhea were not more likely to be CaCV positive.

Related Research Articles

<i>Parvoviridae</i> Family of viruses

Parvoviruses are a family of animal viruses that constitute the family Parvoviridae. They have linear, single-stranded DNA (ssDNA) genomes that typically contain two genes encoding for a replication initiator protein, called NS1, and the protein the viral capsid is made of. The coding portion of the genome is flanked by telomeres at each end that form into hairpin loops that are important during replication. Parvovirus virions are small compared to most viruses, at 23–28 nanometers in diameter, and contain the genome enclosed in an icosahedral capsid that has a rugged surface.

<i>Carnivore protoparvovirus 1</i> Species of parvovirus

Carnivore protoparvovirus 1 is a species of parvovirus that infects carnivorans. It causes a highly contagious disease in both dogs and cats separately. The disease is generally divided into two major genogroups: FPV containing the classical feline panleukopenia virus (FPLV), and CPV-2 containing the canine parvovirus type 2 (CPV-2) which appeared in the 1970s.

Porcine circoviral disease (PCVD), also known as porcine circovirus associated disease (PCVAD), is a disease seen in domestic pigs. This disease causes illness in piglets, with clinical signs including progressive loss of body condition, visibly enlarged lymph nodes, difficulty in breathing, and sometimes diarrhea, pale skin, and jaundice. PCVD is very damaging to the pig-producing industry and has been reported worldwide. PCVD is caused by Porcine circovirus 2 (PCV-2).

<span class="mw-page-title-main">Canine parvovirus</span> Contagious virus mainly affecting dogs

Canine parvovirus is a contagious virus mainly affecting dogs. CPV is highly contagious and is spread from dog to dog by direct or indirect contact with their feces. Vaccines can prevent this infection, but mortality can reach 91% in untreated cases. Treatment often involves veterinary hospitalization. Canine parvovirus often infects other mammals including foxes, wolves, cats, and skunks. Felines (cats) are also susceptible to panleukopenia, a different strain of parvovirus.

Canid alphaherpesvirus 1 (CaHV-1), formerly Canine herpesvirus (CHV), is a virus of the family Herpesviridae which most importantly causes a fatal hemorrhagic disease in puppies less than two to three weeks old. It is known to exist in the United States, Canada, Australia, Japan, England and Germany. CHV was first recognized in the mid-1960s from a fatal disease in puppies.

<span class="mw-page-title-main">Porcine circovirus</span> Species of virus

Porcine circovirus (PCV) is a group of four single-stranded DNA viruses that are non-enveloped with an unsegmented circular genome. They are members of the genus Circovirus that can infect pigs. The viral capsid is icosahedral and approximately 17 nm in diameter.

<span class="mw-page-title-main">Duck plague</span> Disease caused by Anatid alphaherpesvirus 1

Duck plague is a worldwide disease caused by Anatid alphaherpesvirus 1 (AnHV-1) of the family Herpesviridae that causes acute disease with high mortality rates in flocks of ducks, geese, and swans. It is spread both vertically and horizontally—through contaminated water and direct contact. Migratory waterfowl are a major factor in the spread of this disease as they are often asymptomatic carriers of disease. The incubation period is three to seven days. Birds as young as one week old can be infected. DEV is not zoonotic.

Carnivore bocaparvovirus 1, formerly Canine minute virus is a species of Bocaparvovirus of the family Parvoviridae that infects dogs. It is similar to bovine parvovirus in its protein structure and DNA. A virus causing respiratory disease in humans has been called human bocavirus due to its similarity to these viruses. Canine minute virus was originally discovered in Germany in 1967 in military dogs, although it was originally thought to not cause disease. Dogs and puppies are infected orally, and the virus is spread transplacentally to the fetuses. Symptoms are seen most commonly between the ages of one to three weeks and include severe diarrhea, difficulty breathing, and anorexia. In severe cases, illness can be fatal.

<span class="mw-page-title-main">Bacteriophage MS2</span> Species of virus

Bacteriophage MS2, commonly called MS2, is an icosahedral, positive-sense single-stranded RNA virus that infects the bacterium Escherichia coli and other members of the Enterobacteriaceae. MS2 is a member of a family of closely related bacterial viruses that includes bacteriophage f2, bacteriophage Qβ, R17, and GA.

<span class="mw-page-title-main">Veterinary virology</span> Study of viruses affecting animals

Veterinary virology is the study of viruses in non-human animals. It is an important branch of veterinary medicine.

Gyrovirus is a genus of viruses, in the family Anelloviridae. Until 2011, chicken anemia virus was the only Gyrovirus identified, but since then gyroviruses have also been identified in humans. Diseases associated with this genus include: chicken infectious anemia, which is associated with depletion of cortical thymocytes and erythroblastoid cells.

<span class="mw-page-title-main">Virus</span> Infectious agent that replicates in cells

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. Viruses are found in almost every ecosystem on Earth and are the most numerous type of biological entity. Since Dmitri Ivanovsky's 1892 article describing a non-bacterial pathogen infecting tobacco plants and the discovery of the tobacco mosaic virus by Martinus Beijerinck in 1898, more than 11,000 of the millions of virus species have been described in detail. The study of viruses is known as virology, a subspeciality of microbiology.

Human bocavirus (HBoV) is the name given to all viruses in the genus Bocaparvovirus of virus family Parvoviridae that are known to infect humans. HBoV1 and HBoV3 are members of species Primate bocaparvovirus 1 whereas viruses HBoV2 and HBoV4 belong to species Primate bocaparvovirus 2. Some of these viruses cause human disease. HBoV1 is strongly implicated in causing some cases of lower respiratory tract infection, especially in young children, and several of the viruses have been linked to gastroenteritis, although the full clinical role of this emerging infectious disease remains to be elucidated.

<span class="mw-page-title-main">Bacteriophage Qbeta</span> Species of virus

Bacteriophage Qbeta, commonly referred to as Qbeta or Qβ, is a positive-strand RNA virus which infects bacteria that have F-pili, most commonly Escherichia coli. Its linear genome is packaged into an icosahedral capsid with a diameter of 28 nm. Bacteriophage Qβ enters its host cell after binding to the side of the F-pilus.

Bocaparvovirus is a genus of viruses in the subfamily Parvovirinae of the virus family Parvoviridae. Humans, cattle, and dogs serve as natural hosts. There are 28 species in this genus. Diseases associated with this genus include, in humans, acute respiratory illness, and in cattle, diarrhea and mild respiratory symptoms.

<i>Circovirus</i> Genus of viruses

Circovirus is a genus of viruses, in the family Circoviridae. Birds and pigs serve as natural hosts, though dogs have been shown to be infected as well. It is a single stranded DNA virus (ssDNA). There are 49 species in this genus. Some members of this genus cause disease: PCV-1 is non pathogenic, while PCV-2 causes postweaning multisystemic wasting syndrome (PMWS).

<i>Spiroplasma phage 1-R8A2B</i> Species of virus

Spiroplasma phage 1-R8A2B is a filamentous bacteriophage in the genus Vespertiliovirus of the family Plectroviridae, part of the group of single-stranded DNA viruses. The virus has many synonyms, such as SpV1-R8A2 B, Spiroplasma phage 1, and Spiroplasma virus 1, SpV1. SpV1-R8A2 B infects Spiroplasma citri. Its host itself is a prokaryotic pathogen for citrus plants, causing Citrus stubborn disease.

<i>Protoparvovirus</i> Genus of viruses

Protoparvovirus is a genus of viruses in the Parvovirinae subfamily of the virus family Parvoviridae. Vertebrates serve as natural hosts. There are 15 species in the genus including Rodent protoparvovirus 1 for which the exemplar virus is minute virus of mice (MVM). This genus also includes canine parvovirus (CPV), which causes gastrointestinal tract damage in puppies that is about 80% fatal, and porcine parvovirus (PPV), which is a major cause of fetal death and infertility in pigs. The genus divides phylogenetically into two branches, one that contains many founder members of the family, such as MVM, CPV and PPV, which have been studied in considerable detail, and a second branch occupied exclusively by predicted viruses whose coding sequences were identified recently in the wild using virus discovery approaches, but whose biology remains minimally explored. This second branch currently contains two species whose members infect humans, called Primate protoparvovirus 1 and Primate protoparvovirus 3. Until 2014, the genus was called Parvovirus, but it was renamed to eliminate confusion between members of this genus and members of the entire family Parvoviridae.

Mammalian orthoreovirus (MRV) is a double-stranded RNA virus. It is a part of the family Reoviridae, as well as the subfamily Spinareovirinae. As seen in the name, the Mammalian Ortheoreovirus infects numerous mammalian species and vertebrates which serve as natural hosts. Some diseases that occur as a result of this virus or are associated with this virus include mild upper respiratory illness, and gastrointestinal illness. Examples of these are: upper respiratory tract syndromes, gastroenteritis, biliary atresia, obstructive hydrocephalus, jaundice, alopecia, conjunctivitis, and ‘oily hair’ associated with steatorrhea.

<i>Monodnaviria</i> Realm of viruses

Monodnaviria is a realm of viruses that includes all single-stranded DNA viruses that encode an endonuclease of the HUH superfamily that initiates rolling circle replication of the circular viral genome. Viruses descended from such viruses are also included in the realm, including certain linear single-stranded DNA (ssDNA) viruses and circular double-stranded DNA (dsDNA) viruses. These atypical members typically replicate through means other than rolling circle replication.

References

  1. ↑ Rosario, Karyna; Breitbart, Mya; Harrach, Balázs; Segalés, Joaquim; Delwart, Eric; Biagini, Philippe; Varsani, Arvind (2017-05-01). "Revisiting the taxonomy of the family Circoviridae: establishment of the genus Cyclovirus and removal of the genus Gyrovirus". Archives of Virology. 162 (5): 1447–1463. doi: 10.1007/s00705-017-3247-y . ISSN   0304-8608. PMID   28155197.
  2. ↑ Kapoor, Amit; Dubovi, Edward J.; Henriquez-Rivera, Jose Angel; Lipkin, W. Ian (2012-06-15). "Complete Genome Sequence of the First Canine Circovirus". Journal of Virology. 86 (12): 7018. doi:10.1128/jvi.00791-12. ISSN   0022-538X. PMC   3393582 . PMID   22628401.
  3. ↑ Ruiz-Masó, J. A.; MachóN, C.; Espinosa, M.; Solar, G. Del; Bordanaba-Ruiseco, L.; Coll, M. (2015-02-20). "Plasmid Rolling-Circle Replication". Microbiology Spectrum. 3 (1): PLAS–0035–2014. doi: 10.1128/microbiolspec.plas-0035-2014 . hdl: 10261/111631 . ISSN   2165-0497. PMID   26104557.
  4. ↑ Zaccaria, Guendalina; Malatesta, Daniela; Scipioni, Gabriella; Felice, Elisabetta Di; Campolo, Marco; Casaccia, Claudia; Savini, Giovanni; Sabatino, Daria Di; Lorusso, Alessio (2016). "Circovirus in domestic and wild carnivores: An important opportunistic agent?". Virology. 490: 69–74. doi: 10.1016/j.virol.2016.01.007 . PMID   26848830.
  5. ↑ Li, Linlin; McGraw, Sabrina; Zhu, Kevin; Leutenegger, Christian M.; Marks, Stanley L.; Kubiski, Steven; Gaffney, Patricia; Jr, Florante N. Dela Cruz; Wang, Chunlin (2013). "Circovirus in Tissues of Dogs with Vasculitis and Hemorrhage". Emerging Infectious Diseases. 19 (4): 534–541. doi:10.3201/eid1904.121390. PMC   3647419 . PMID   23628223.
  6. ↑ Thaiwong, T.; Wise, A. G.; Maes, R. K.; Mullaney, T.; Kiupel, M. (2016-05-06). "Canine Circovirus 1 (CaCV-1) and Canine Parvovirus 2 (CPV-2)". Veterinary Pathology. 53 (6): 1204–1209. doi: 10.1177/0300985816646430 . PMID   27154544.
  7. ↑ Decaro, Nicola; Martella, Vito; Desario, Costantina; Lanave, Gianvito; Circella, Elena; Cavalli, Alessandra; Elia, Gabriella; Camero, Michele; Buonavoglia, Canio (2014-08-22). "Genomic Characterization of a Circovirus Associated with Fatal Hemorrhagic Enteritis in Dog, Italy". PLOS ONE. 9 (8): e105909. Bibcode:2014PLoSO...9j5909D. doi: 10.1371/journal.pone.0105909 . ISSN   1932-6203. PMC   4141843 . PMID   25147946.
  8. ↑ Hsu, Han-Siang; Lin, Ting-Han; Wu, Hung-Yi; Lin, Lee-Shuan; Chung, Cheng-Shu; Chiou, Ming-Tang; Lin, Chao-Nan (2016-06-17). "High detection rate of dog circovirus in diarrheal dogs". BMC Veterinary Research. 12 (1): 116. doi: 10.1186/s12917-016-0722-8 . ISSN   1746-6148. PMC   4912760 . PMID   27315792.
  9. ↑ Li, Linlin; McGraw, Sabrina; Zhu, Kevin; Leutenegger, Christian M.; Marks, Stanley L.; Kubiski, Steven; Gaffney, Patricia; Jr, Florante N. Dela Cruz; Wang, Chunlin (2013). "Circovirus in Tissues of Dogs with Vasculitis and Hemorrhage". Emerging Infectious Diseases. 19 (4): 534–541. doi:10.3201/eid1904.121390. PMC   3647419 . PMID   23628223.
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