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. 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.
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. 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
Rolling circle replication 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. 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.