Porcine circovirus

Last updated

Contents

Porcine circovirus
Circovirus virion.jpg
Scientific classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Monodnaviria
Kingdom: Shotokuvirae
Phylum: Cressdnaviricota
Class: Arfiviricetes
Order: Cirlivirales
Family: Circoviridae
Genus: Circovirus
Groups included
Cladistically included but traditionally excluded taxa

(See Circovirus)

Porcine circovirus (PCV) is a group of four [1] single-stranded DNA viruses that are non-enveloped with an unsegmented circular genome. They are members of the genus Circovirus that can infect pigs. [2] The viral capsid is icosahedral and approximately 17 nm in diameter.

PCVs are the smallest viruses replicating autonomously in eukaryotic cells. [3] They replicate in the nucleus of infected cells, using the host polymerase for genome amplification.

PCV-2 causes Porcine circovirus associated disease or postweaning multisystemic wasting syndrome (PMWS). An effective vaccination is now available. Fort Dodge Animal Health (Wyeth) launched the first USDA approved vaccine in 2006, containing an inactivated virus (ATCvet code: QI09AA07 ( WHO )). [2]

Classification

Three strains of PCV are known as of 2018:

PCV-1 and PCV-2 show a high degree of sequence identity and a similar genomic organisation; nevertheless, the basis of the distinct pathogenicity has not yet been unravelled. [3] The organization for PCV-3 is similar, but the sequence identity is much lower. [4]

Genome

Genome map of PCV-1 (identical with PCV-2) Circovirus genome.jpg
Genome map of PCV-1 (identical with PCV-2)
"Melting Pot" quadruplet formation PCVmeltingpot.jpg
”Melting Pot” quadruplet formation

PCV's genome is one of the simplest of all viruses, requiring only a capsid protein (ORF2) and two replicase proteins (ORF1) in order to replicate and produce a functional virus. Due to the simplicity of PCV, it must rely heavily on the host's cellular machinery to replicate. The origin of replication is located on a small octanucleotide stem-loop that is flanked by palindromic repeats, [5] with the ORF's being located head-to-head on both sides of the Ori. Specifically, ORF1 is located clockwise and ORF2 is located counterclockwise of the Ori.

The two replicase enzymes that are created from ORF1, Rep and Rep', are conserved between the two types of PCV, and are part of the early phase of the virus. The replicases differ in that Rep is the full ORF1 transcript of 312 amino acids, whereas Rep' is a truncated form of ORF1 as a result of splicing and is only 168 amino acids in length. The promoter for rep (Prep) contains an Interferon-Stimulated Response Element (ISRE) that suggests Rep and Rep' are regulated by cytokine involvement, [6] and is probably a means for the virus to overcome the host's immune responses to infection. Rep and Rep' form a dimer that binds to two hexameric regions adjacent to the stem-loop, H1 and H2, which is required for replication. When the dimer binds to this region, the replicases cleave the loop region of the stem-loop and remain covalently bound to the H1 and H2 regions of the DNA, which becomes the 5' end of the DNA. The newly formed 3'OH end forms a primer using host RNA polymerase, which is then used by the host's DNA polymerase to begin transcription of the viral DNA via rolling circle replication. After the complementary DNA strand has been created, the stem region of the stem-loop forms a loose, non-hydrogen bonded, quadruplet DNA structure. This loosely associated structure can form short lived DNA-trimers which forms two templates for replication, as well as maintaining the nucleic integrity of the stem region of the stem-loop. [5] The termination of the replication sequence has not been identified, yet, though there is evidence supporting that Rep also represses its own promoter, Prep.

The ORF2 region encodes the capside protein Cap (aka CP), which differs slightly between PCV-1 and PCV-2. This variation within PCV may explain why PCV-1 is non-pathogenic, while PCV-2 is pathogenic[ contradictory ]. The promoter for this protein is located within ORF1, within the site where Rep' is truncated, and is splice from the same exon to the starting point of the ORF2 coding region [6] and expressed during both early and late phases. This is the immunogenic region of the virus and is the primary area of research for creating a vaccine to treat PMWS.

There is a third gene encoded in the opposite orientation to ORF1 in the genome. This gene is transcribed and is an essential gene involved in viral replication. [7]

Size

Porcine circovirus is a replicating entity with one of the smallest DNA strands consisting of a simple loop of DNA.

The DNA sequence for Porcine circovirus type 2 strain MLP-22 is 1726 base pairs long. [8] [9]

Entry

PCV infects a wide variety of cell types, including hepatocytes, cardiomyocytes, and macrophages. However, until recently, it was unknown exactly how attachment and entry into these cells was achieved. Research has shown that PCV utilizes clathrin-mediated endocytosis to enter the cell, though it's stipulated that there may still be other factors that haven't been identified. Once endocytosed, the endosome and lysosome formation causes an acidic pH shift, which allows ATP-driven uncoating of the virus and allows it to escape the endosomes and lysosomes. After the virus escapes the endosomes and lysosomes, it travels to the nucleus through unknown means. [10]

Escape

Besides ORF1 and ORF2, there is also an ORF3 which is not necessarily required for PCV to survive within the host. Research has shown that the protein coded in ORF3 can modulate the host cell's cell-division cycle and cause cell-mediated, virus-induced apoptosis. Using a yeast two-hybrid screening system of ORF3 against the porcine cDNA library indicated that the ORF3 protein interacts with the porcine pPirh2, which is an E3 ubiquitin ligase. This E3 ubiquitin ligase normally interacts with p53 during the cell division cycle and prevents it from halting the cell division cycle at S-phase. However, ORF3 also interacts with pPirh2 at the same region as p53 and causes an upregulation of p53 expression. This increase in p53 stops the cell division cycle and the result of this is p53 mediated apoptosis, which releases PCV into the extracellular environment. [11]

Contamination in human vaccine

On March 22, 2010, the U.S. Food and Drug Administration (FDA) recommended suspending the use of Rotarix, one of two vaccines licensed in the United States against rotavirus, due to findings of viral DNA contamination. [12] Follow-up work by GlaxoSmithKline confirmed the contamination in working cells and the viral "seed" used in Rotarix production, also confirming the material was likely present since the early stages of product development, including the clinical trials for FDA approval. [13]

Testing of the other licensed vaccine against rotavirus infection, RotaTeq, also detected some components of both PCV-1 and PCV-2. [14] Porcine circovirus 1 is not known to cause disease in humans or other animals. [12] [13]

As of June 8, 2010, the FDA has, based on a careful review of a variety of scientific information, determined it is appropriate for clinicians and public health professionals in the United States to use both Rotarix and RotaTeq vaccine. [15]

See also

Related Research Articles

<span class="mw-page-title-main">Poliovirus</span> Enterovirus

Poliovirus, the causative agent of polio, is a serotype of the species Enterovirus C, in the family of Picornaviridae. There are three poliovirus serotypes: types 1, 2, and 3.

<span class="mw-page-title-main">Defective interfering particle</span>

Defective interfering particles (DIPs), also known as defective interfering viruses, are spontaneously generated virus mutants in which a critical portion of the particle's genome has been lost due to defective replication or non-homologous recombination. The mechanism of their formation is presumed to be as a result of template-switching during replication of the viral genome, although non-replicative mechanisms involving direct ligation of genomic RNA fragments have also been proposed. DIPs are derived from and associated with their parent virus, and particles are classed as DIPs if they are rendered non-infectious due to at least one essential gene of the virus being lost or severely damaged as a result of the defection. A DIP can usually still penetrate host cells, but requires another fully functional virus particle to co-infect a cell with it, in order to provide the lost factors.

<span class="mw-page-title-main">Oncovirus</span> Viruses that can cause cancer

An oncovirus or oncogenic virus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, when the term "oncornaviruses" was used to denote their RNA virus origin. With the letters "RNA" removed, it now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus". The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the retinoblastoma protein.

Circoviridae is a family of DNA viruses. Birds and mammals serve as natural hosts. There are 101 species in this family, assigned to 2 genera. Diseases associated with this family include: PCV-2: postweaning multisystemic wasting syndrome; CAV: chicken infectious anemia.

<i>Barnaviridae</i> Family of viruses

Barnaviridae is a family of non-enveloped, positive-strand RNA viruses. Cultivated mushrooms serve as natural hosts. The family has one genus, Barnavirus, which contains one species: Mushroom bacilliform virus. Diseases associated with this family includes La France disease.

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).

Betaarterivirus suid 1, commonly Porcine reproductive and respiratory syndrome virus (PRRSV), is a virus that causes a disease of pigs, called porcine reproductive and respiratory syndrome (PRRS), also known as blue-ear pig disease. This economically important, panzootic disease causes reproductive failure in breeding stock and respiratory tract illness in young pigs.

HHV Latency Associated Transcript is a length of RNA which accumulates in cells hosting long-term, or latent, Human Herpes Virus (HHV) infections. The LAT RNA is produced by genetic transcription from a certain region of the viral DNA. LAT regulates the viral genome and interferes with the normal activities of the infected host cell.

<i>Pestivirus</i> Genus of viruses

Pestivirus is a genus of viruses, in the family Flaviviridae. Viruses in the genus Pestivirus infect mammals, including members of the family Bovidae and the family Suidae. There are 11 species in this genus. Diseases associated with this genus include: hemorrhagic syndromes, abortion, and fatal mucosal disease.

Porcine parvovirus (PPV), a virus in the species Ungulate protoparvovirus 1 of genus Protoparvovirus in the virus family Parvoviridae, causes reproductive failure of swine characterized by embryonic and fetal infection and death, usually in the absence of outward maternal clinical signs. The disease develops mainly when seronegative dams are exposed oronasally to the virus anytime during about the first half of gestation, and conceptuses are subsequently infected transplacentally before they become immunocompetent. There is no definitive evidence that infection of swine other than during gestation is of any clinical or economic significance. The virus is ubiquitous among swine throughout the world and is enzootic in most herds that have been tested. Diagnostic surveys have indicated that PPV is the major infectious cause of embryonic and fetal death. In addition to its direct causal role in reproductive failure, PPV can potentiate the effects of porcine circovirus type II (PCV2) infection in the clinical course of postweaning multisystemic wasting syndrome (PMWS).

<span class="mw-page-title-main">Herpes simplex virus</span> Species of virus

Herpes simplex virus1 and 2, also known by their taxonomic names Human alphaherpesvirus 1 and Human alphaherpesvirus 2, are two members of the human Herpesviridae family, a set of viruses that produce viral infections in the majority of humans. Both HSV-1 and HSV-2 are very common and contagious. They can be spread when an infected person begins shedding the virus.

<span class="mw-page-title-main">Psittacine beak and feather disease</span> Viral disease affecting parrots

Psittacine beak and feather disease (PBFD) is a viral disease affecting all Old World and New World parrots. The causative virus—beak and feather disease virus (BFDV)—belongs to the taxonomic genus Circovirus, family Circoviridae. It attacks the feather follicles and the beak and claw matrices of the bird, causing progressive feather, claw and beak malformation and necrosis. In later stages of the disease, feather shaft constriction occurs, hampering development until eventually all feather growth stops. It occurs in an acutely fatal form and a chronic form.

Anelloviridae is a family of viruses. They are classified as vertebrate viruses and have a non-enveloped capsid, which is round with isometric, icosahedral symmetry and has a triangulation number of 3.

<i>Sobemovirus</i> Genus of viruses

Sobemovirus is a genus of non-enveloped, positive-strand RNA viruses which infect plants.. Plants serve as natural hosts. There are 21 species in this genus. Diseases associated with this genus include: mosaics and mottles.

<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).

This glossary of virology is a list of definitions of terms and concepts used in virology, the study of viruses, particularly in the description of viruses and their actions. Related fields include microbiology, molecular biology, and genetics.

Canine circovirus, 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 was the first Circovirus to be identified that infects a mammal species other than pigs.

Torque teno sus virus, belonging to the family Anelloviridae, is a group of virus strains that are non-enveloped, with a single-stranded circular DNA genome ranging from 2.6 to 2.8 kb in size. These swine infecting anelloviruses are divided into two genera: Iotatorquevirus and Kappatorquevirus. Torque teno sus virus has been found in pigs worldwide. TTSuVs are mainly transmitted by fecal-oral route. The prevalence of these viruses is relatively high. For now, there is not known disease caused exclusively by TTSuV. There is the possibility that TTSuV may worsen the progression of other diseases and therefore increase the economic losses for pig industry.

<i>Redondoviridae</i> Family of viruses

Redondoviruses are a family of human-associated DNA viruses. Their name derives from the inferred circular structure of the viral genome . Redondoviruses have been identified in DNA sequence based surveys of samples from humans, primarily samples from the oral cavity and upper airway.

<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. "Virus Taxonomy: 2020 Release". International Committee on Taxonomy of Viruses (ICTV). March 2021. Retrieved May 11, 2021.
  2. 1 2 3 4 Ellis, J (March 2014). "Porcine circovirus: a historical perspective". Veterinary Pathology. 51 (2): 315–327. doi:10.1177/0300985814521245. PMID   24569612. S2CID   1406680.
  3. 1 2 3 Mankertz P (2008). "Molecular Biology of Porcine Circoviruses". Animal Viruses: Molecular Biology. Caister Academic Press. ISBN   978-1-904455-22-6.
  4. 1 2 Klaumann, Francini; Correa-Fiz, Florencia; Franzo, Giovanni; Sibila, Marina; Núñez, José I.; Segalés, Joaquim (December 12, 2018). "Current Knowledge on Porcine circovirus 3 (PCV-3): A Novel Virus With a Yet Unknown Impact on the Swine Industry". Frontiers in Veterinary Science. 5: 315. doi: 10.3389/fvets.2018.00315 . PMC   6315159 . PMID   30631769.
  5. 1 2 F. Faurez; et al. (May 2009). "Replication of porcine circoviruses". Virology Journal . 6: 60. doi: 10.1186/1743-422X-6-60 . PMC   2690592 . PMID   19450240.
  6. 1 2 A. Mankertz; et al. (2004). "Molecular biology of "Porcine circovirus": analyses of gene expression and viral replication". Veterinary Microbiology . 98 (2): 81–88. doi:10.1016/j.vetmic.2003.10.014. PMID   14741119.
  7. He JL, Dai D, Zhou N, Zhou JY (2012) Analysis of Putative ORF3 Gene Within Porcine Circovirus Type 2. Hybridoma (Larchmt) 31(3):180-187
  8. "Genomes - Genome - NCBI". www.ncbi.nlm.nih.gov. Retrieved December 27, 2018.
  9. Mukherjee,P., Sen,A., Das,S., Milton,A.P., Shakuntala,I., Ghatak,S., Barkalita,L.M. and Borah,P. "Porcine circovirus 2 strain MLP-22, complete genome". www.ncbi.nlm.nih.gov. Retrieved April 21, 2018.{{cite web}}: CS1 maint: multiple names: authors list (link)
  10. J. Liu; et al. (September 2007). "The ORF3 Protein of Porcine Circovirus Type 2 Interacts with Porcine Ubiquitin E3 Ligase Pirh2 and Facilitates p53 Expression in Viral Infection". Journal of Virology . 81 (71): 9560–9567. doi:10.1128/JVI.00681-07. PMC   1951394 . PMID   17581998.
  11. G. Misinzo; et al. (July 2005). "Binding and entry characteristics of porcine circovirus 2 in ceslls of the porcine monocytic line 3D4/31". Journal of General Virology . 86 (7): 2057–2068. doi: 10.1099/vir.0.80652-0 . PMID   15958685.
  12. 1 2 "Components of Extraneous Virus Detected in Rotarix Vaccine; No Known Safety Risk", U.S. Food and Drug Administration, March 22, 2010
  13. 1 2 "Detection of DNA from PCV1 in Rotarix", FDA
  14. "DNA of Pig Viruses Found in Merck Vaccine", The Wall Street Journal , May 7, 2010
  15. "Update on Rotavirus Vaccines". fda.gov. Retrieved December 27, 2018.