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Family: Picornaviridae

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=Introduction:= This wikispace was developed in order to find resources and analyzing the information in order to organize it in a succinct manner. The hope is that the most valuable information of the virus family, picornaviridae, is contained within this page. However, the resources contained in this page should also allow those interested in going further a good starting place for their own research. I will start with a definition of the virus and then some specifics on its physical structure and chemical makeup. The second part of this wiki will be dedicated to how the virus behaves in nature; such as, its life cycle, host range, its taxonomy, pathology, antigenicity, the host immune response and the viruses response to that, and finally some of the most important or prevalent members of the family.

=Definition:= Picornaviridae comes from the Latin word "pico" meaning small and from the type of genome it carries (RNA); resulting in the name small-RNA-virus. This is a family of plus sense single stranded RNA (+ssRNA) naked viruses. Because of this it is placed into group IV in the Baltimore classification system. Plus sense RNA viruses are capable of acting as mRNA upon entering the host and can use the host's polymerases to begin protein synthesis. A "Naked virus" simply implies that it lacks a lipid envelope around their protein capsid. (source)(NCBI)

=Morphology=


 * Piornaviridae has a spherecal icosohedral shape as seen in the bottom row.
 * The simplest icosohedron has 12 vertices and 20 faces
 * 12 pentons form the vertices of the 5 fold symmetry, and 20 hextons assemble to form the capsid
 * 5-3-2 axes of symmetry
 * Picornaviridae has 32 capsomers (subunits VP1-4)
 * 22-30nm diameter
 * "Naked" (no lipid envelope)

[|NCBI]

=Physical and Physiochemical Properties=
 * Molecular Weight: 2x10 6 - 3x10 6
 * Bouyant Density: Useful for distinguishing between viruses
 * Enterovirus: 1.33-1.34 g/ml CsCl
 * Rhinovirus: 1.38-1.42 g/ml CsCl
 * Inactivated by:
 * pasteurization, boiling, formalin treatment, chlorine
 * Enteroviruses are stabilized to heat by treatment with MgCl 2
 * Resistant to lipid solvents (ethers), because there are no essential lipids for capsid formation
 * Polyprotein Molecular Weight: 2.4x10 5 -2.5x10 5

Chemistry
===Nucleic Acid and Genome===


 * Linear and monopartite meaning it is a single part.
 * 7-9kbp (x10 3 ) genome
 * Internal Ribosomal Entry Site (IRES). This RNA structure causes the robosome to be blocked allowing an internal mechanism to open up the reading frame for the polyprotein.
 * VPg (instead of a methylated cap like other genomes) at the 5' end and plyadenylated (polly A) tail at the 3' end

Proteins
NCBI
 * No viral proteins or enzymes other than VPg
 * VPg protein cap at 5' end of genome
 * Coded proteins are initially a polyprotein then cleaved to produce:
 * Structural proteins: Necessary for capsid formation [[image:usfpicornaviridaewillkammel/CD155.png width="255" height="274" align="right" caption="(purple) poliovirus receptor (CD155), (blue, green, gray, brown) VP1-4 structural proteins."]]
 * VP1, VP2 and VP3 are external, VP4 is internal
 * Non structural proteins: Necessary for protein processing, host shut-off, replication, and host cell lysis.
 * 3D pol (an RNA dependent RNA polymerase or RdRp), 3C pro (protease), VPg (allows the RNA to be "uncapped" and thus transcribed by host ribosomes), 2A (cleaves P1 from P2), 2B, 2C, 3A,

Lipids

 * No essential lipids in the protein coat

Carbohydrates

 * Requries glycoprotein receptors on the host.
 * CD155 (coded by the PVR gene and typically used in cellular adhesion) for poliovirus whost typical function is the interaction at adherens junctions between epithelial cells.
 * PVR and similar receptors for other enterovirus
 * ICAM-1 ((Intracellular Adhesion Molecule)CD54) for rhinovirus located on respiritory epithelial cells.

NCBI Structure

=Life Cycle= Virions gain entry though epthelium of the upper respiritory tract or along the alimentary tract. As with any virus, picornaviruses must gain entry (adsorption), multiply (protein synthesis, RNA replication, and assembly), and egress (exit the host cell). Many picornaviruses can withstand low pH conditions such as within the stomach which allows the viruses to gain entry to the lower alimentary system. In order for adsorption to occur, the virion must come into contact with a cell surface receptor on the target cell. The Poliovirus receptor is CD155 which is a large cell surface macromolecule used for cellular adhesion(1). Once contact has been established, the protein coat of the virus uncoats and the lipid membrane of the host cell is altered to allow entry of the virus genome through receptor mediated endocytosis(2). Within the cytoplasm of the host cell, the VPg cap is cleaved by a cellular phosphdiesterase and direct translation of the viral RNA (which acts as mRNA) is performed by host cell robosomes when associated with the IRES region(3). Because the genome is a monopartite (one complete strand) the entire RNA sequence is read and translated into a polyprotein. The polyprotein contains all the proteins the genome codes for. the protein requires cleaving in order to obtain functional viral proteins. Proteolytic cleavage (both auto enzymatic and cellular proteosome cleavage occurs) produces mature structural and non structural proteins (4). During this process, proteosomes are created which aid in the inhibition of host cell protein synthesis. This is done by digestion of the translation initiation factor eIF-4G. Upon degredation of this factor, ribosomes are unable to recognize and translate capped (metthylated) mRNA and as a result the uncapped viral mRNA will be preferentially translated. Mature proteins include an RNA polymerase which can transcribe the + sense viral RNA into a - sense strand that serves as a template for more + sense RNA. The synthesis of - sense RNA takes place within the host endoplasmic reticulum where it produces double stranded RNA or replicative form (RF). The complete ribonucleic protein complex with RNA and accociated polymerase complexes is termed the replicative intermediate (RI). This process leads to an increased number of viral genomes and viral proteins (5-7). Once enough protein and RNA has been synthesized, 60 coppies of each of the structural proteins, VP0, VP1, and VP3 come together to form a procapsid. Viral RNA associates with the procapsid and induces the cleavage of VP0 into VP2 and VP4. These proteins allow the procapsid to change its conformation into a thermodynamically stable structure which protects the RNA from proteolytic degredation (8). These mature virions and their protein products eventually result in lysis of the host cell and the ultimate goal of escaping and infecting other target cells (9).

(Virology Journal) ([|NCBI-Book])

Hosts
Picornaviridae viruses infect many vertebrate hosts including: humans, cloven-hoofed animals, and rodents. Poliovirus is exclusivly seen in humans but reaches a dead end if it results in paralysis as that virus cannot infect other hosts. Foot and mouth disease virus typically only infects cloven-hoofed animals but has been documented to infect humans.

=Taxonomy= Although there are systems of classification, the upper levels of classification are broad groupings of similar viruses due to their genome or structure but lacking a single defining criteria. The lower levels change frequently with the appearance of new isolates, strains, and serotypes as it is necessary to place them in their respective group. Most sources agree that there are 12 genera within the family picornaviridae as seen below. (source)
 * Order: Picornavirales (5 Families)
 * Family: //Dicistroviridae (2 Genera)//
 * //Iflaviridae (1 Genera)//
 * //Marnaviridae (1 Genera)//
 * //Secoviridae (1 Subfamily and 5 Genera not in a Subfamily)//
 * Picornaviridae (12 Genera)
 * Genera:
 * //Aphthovirus//
 * //Species: Bovine rhinitis B virus//
 * //Equine rhinitis A virus//
 * **//Foot-and-mouth disease virus// **
 * //Avihepatovirus//
 * //Species:// //Duck hepatitis A virus//
 * //Cardiovirus//
 * Species: //Encephalomyocarditis virus//
 * //Theilovirus//
 * //Enterovirus//
 * <span class="TreeControl_text_name"><span class="TreeControl_text_name">//Species:// //Bovine enterovirus//
 * <span class="TreeControl_text_name">//Human enterovirus A-D//
 * <span class="TreeControl_text_name">//Enterovirus C//
 * <span class="TreeControl_text_name">//**Poliovirus** (3 serotypes)//
 * <span class="TreeControl_text_name">//**Human rhinovirus** A-C (100+ serotypes)//
 * <span class="TreeControl_text_name">//Porcine enterovirus B//
 * <span class="TreeControl_text_name">//Simian enterovirus A//
 * <span class="TreeControl_text_name">//Erbovirus//
 * <span class="TreeControl_text_name"><span class="TreeControl_text_name">//Species:// //Equine rhinitis B virus//
 * <span class="TreeControl_text_name">//Hepatovirus//
 * Species: **<span class="TreeControl_text_name">//Hepatitis A virus// **
 * <span class="TreeControl_text_name">//Kobuvirus//
 * Species: <span class="TreeControl_text_name">//Aichi virus//
 * <span class="TreeControl_text_name">//Bovine kobuvirus//
 * <span class="TreeControl_text_name">//Parechovirus//
 * <span class="TreeControl_text_name"><span class="TreeControl_text_name">//Species:// //Human parechovirus//
 * <span class="TreeControl_text_name">//Ljungan virus//
 * <span class="TreeControl_text_name">//Sapelovirus//
 * <span class="TreeControl_text_name"><span class="TreeControl_text_name">//Species:// //Avian sapelovirus//
 * <span class="TreeControl_text_name">//Porcine sapelovirus//
 * <span class="TreeControl_text_name">//Simian sapelovirus//
 * <span class="TreeControl_text_name">//Senecavirus//
 * <span class="TreeControl_text_name"><span class="TreeControl_text_name">//Species:// //Seneca Valley virus//
 * <span class="TreeControl_text_name">//Teschovirus//
 * <span class="TreeControl_text_name"><span class="TreeControl_text_name">//Species:// //Porcine teschovirus//
 * <span class="TreeControl_text_name">//Tremovirus//
 * <span class="TreeControl_text_name"><span class="TreeControl_text_name">//Species:// //Avian encephalomyelitis virus//

=Pathology= Pathology of picornaviridae typically begins at the upper respiritory tract and ether gains entry through the upper respiritory epithelium or is taken through the digestive system to the intestines where it can gain entry. Here, the virus will infect and multiply within the epithelium and regional lymphoid tissue resulting in symptomatic or asymtomatic respiritory infections. Many pathogens are degraded or killed before reaching the intestines due to proteases or the high pH in the stomach; however, enteroviruses are able to resist environments with a pH of 3-5 due to their protein capsid. Once access is gained the virus will replicate in the mesenteric lymphoid tissue. Viremia may result and be carried by the blood to other organs such as the spinal cord, brain, meninges, heart, muscles, liver, etc. Viruses are spread many ways including: conjunctival secretions, lesion exudates, fecal or oral routes by contamination of inanimate objects, and salivary and respiritory droplets.

Antigenicity
Antigenicity is thought to be due to the highly variable regions of the capsid proteins VP1, VP2, and VP3. These proteins, found in most picorniviridae, are composed of 8 stranded ß-Barrels with random coils connecting the ß-Barrels and making up highly variable antigenic regions. There are no known group specific antigens although there may be slight immunity due to similar antigenic sites. NCBI

Prevention
Poliomyelitis: Salk-type (inactive), or Sabin-type (live) attenuated virus vaccine Hepaitis A: Inactivated Hepaitis A vaccine (Havrix) The biggest need is for public education. Education on the transmition modes (droplet, fecal etc.), personal hygiene, and proper sewage disposal are the most important in decreasing prevelence. Uncantaminated water is especially important for reducing th espread of enteroviruses.

Host
The first immune defense is the production of interferon due to detection of dsRNA. Even though picornaviridae contains ssRNA, during replication the +ssRNA is transcribed into -ssRNA and therefore forms complimentary ssRNA molecules although not a true dsRNA. As a result, a dsRNA replicativeform (RF) is produced (see above life cycle). interferon will lead to a decrease in protein production and thus decrease viral replication (mainly INF alpha and beta). After infection, humoral immunity begins to develop with the production of antibodies (IgA, IgM, and IgG). IgM will prevent the spread of viremia in the blood and will mature for the first 2 weeks. IgG antibodies will peak around 2-3 weeks and will eventually lead to a high specificity serotype specific immunity. This will not likely confer longterm immunity due to the high mutation rate in RNA synthesis. As a result of the high mutation rate, especially within the highly variable antigenic positions, new serotypes continually form. As a result the immune system must start from the beginning to produce another sero specific antibody. Antibodies will lead to neutralization of free virions prohibiting their entry into host cells and will also decrease their shedding in fecal or oral excretions leading to a decreased chance of passing the infection to another individual. The virus/antibody complex will lead to digestion, phagocytosis, or excretion of the virion and ultimatly reduced infection.

Virus
RNA viruses as mentioned above have a much higher mutation rate since it is single stranded and does not have a "proofreading" template strand. This leads to changes in the highly variable antigenic regions resulting in antigenic drift. This phenomenon allows for RNA viruses to continue to adapt to their hosts immune protection and circumvents these blocks. Even if the host has built up an immunological memory to this virus, enough mutations can accumulate which change the viruses serotype and would become unidentifiable by the memory cells. In addition, the host range for picornaviridae is very large and allows the virus to find many different hosts to replicate in. One specific way poliovirus bypasses the host immune response is through the degredation of PKR. PKR as seen in the figure above begins the cascade toward interferon production. As a result of PKR degredation, poliovirus will have a much easier time gaining a foot hold in the host. In addition, poliovirus is able to live in the very acidic environment of the gut and can gain entry into the lymphatic system allowing it a place for rapid multiplication. Foot and mouth disease virus also specifically produces a protein that shuts off host cell protein synthesis which allows the virus to fully utilize all of the host cellular machinary without the cell producing potentially harmful products.

=Important Members= Poliovirus Rhinovirus Hepatitis A Foot-and-mouth disease virus
 * Sequence, Genome, Proteome
 * Host: vertebrates
 * Geogrophy: worldwide
 * Associated Disease: paralysis, summer cold, menengitis, and diarrhea.
 * Transmision: fecal-oral or respiritory route.
 * Vaccination: yes (salk or sabin type)
 * Sequence, Genome, Proteome
 * Host: vertebrates
 * Geogrophy: worldwide
 * Associated Disease: common cold.
 * Transmision: fecal-oral or respiritory route.
 * Antiviral: [|Pleconaril]
 * Sequence, Genome, Proteome
 * Host: vertebrates
 * Liver cells are primary target
 * Geogrophy: worldwide
 * Associated Disease: mild [|hepatitis]and rarely fulminate acute hepatitis
 * Transmision: fecal-oral or blood route.
 * Vaccine: yes
 * Sequence, Genome, Proteome
 * Host: mostly cloven hooved animals but rarely human
 * Geogrophy: worldwide, endemic in parts of Asia, Africa, South America, and the middle east
 * Associated Disease: fever blisters in mouth and feet
 * Transmision: direct or indirect contact and airborne
 * Vaccine: yes

=Areas of Impact:= One potentially area of impact has to do with the question of whether or not to completely eradicate the poliovirus. Although this might sound like a good idea it could have some negative effects. Upon complete eradication of the virus its hosts begin to loose herd immunity. Once herd immunity is lost we are much more susceptible to the infecition if it was to resurface. Our immune systems would have no memory of the infection since we would never have encountered it. Due to this lack of interaction, the virus would likely have a greater impact than it does now. In addition, the question of whether or not to keep a stock of the original virus relates to safety since new vaccines may be needed if an outbreak was to occur, this is seen in the debate over smallpox as well.

=About Wiki Developer= This wiki was developed by Will Kammel, a senior Biology pre-PA major and chem minor at the University of Saint Francis. I am currently enrolled in BIOL 474 which is a virology class. We were assigned a family of viruses and charged with the task of compiling and organizing whatever information we deemed important for the above categories. There is a vast amount of free and accesable information on the web and this is just a scratch on the surface of what can be found.

=Sources=
 * 1) Edward K. Wagner, M. J. (2008). //Basic Virology.// Malden: Blackwell Publishing.
 * 2) Jan Felix Drexler, S. B.-B. (2011). Aichi Virus Shedding in High Concentrations in Patients with Acute Diarrhea. //Emerging Infectious Diseases// //, 17// (8), 1544-1547.
 * 3) Jesus, N. H. (2007, July 10). Epidemics to eradication: the modern history of poliomyelitis. //Virology Journal//.
 * 4) Network, W. I. (n.d.). //Picornaviridae//. Retrieved 0ctober 3, 2011, from wildlife network: http://usgs.wildlifeinformation.org/S/virus/picornaviridae/picornaviridae.htm
 * 5) Portal, B. R. (2009). //Viral Zone//. Retrieved October 6, 2011, from Swiss Institute for Bioinformatics: []
 * 6) S. Goodbourn, L. D. (2000). Interferons: cell signalling, immune modulation, antiviral responses, and virus countermeasures. //Journal of General Virology//, 2341-2364.
 * 7) Thomas Albrecht, J. W. (1996). //Medical Microbiology//. Retrieved September 7, 2011, from NCBI: []