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Poliovirus Receptor 
Polio's first interaction with a host cell consists of binding to a specific cell surface protein, the poliovirus receptor (PVR). The PVR, a cell surface sialylated glycoprotein, is a member of the immunoglobulin superfamily. The defining feature of this superfamily is a "loop" in the protein structure called the Ig domain. PVR has three Ig loops (which are outside the cell), numbered 1-3 starting with the loop farthest from the cell surface. Polio appears to bind to its receptor on loop 1. The receptor molecule binds to a "canyon floor" on the virus particle. The poliovirus receptor is expressed in many human tissue types, including tissues such as kidney that are not normal sites of poliovirus replication. Why doesn't polio replicate in these cells? Possible reasons include a block of viral replication after entry, lack of exposure to those tissues during an infection, or an unknown secondary mediator of viral entry. 

Protein Synthesis 
(Diagram displaying rates of protein synthesis in infected and uninfected cells. The rise in protein synthesis after 2 hours in infected cells is due to viral protein production. Fundamental Virology, p.505) 
The poliovirus genome is made of positive sense single stranded RNA. The genome encodes a single 'polyprotein' of between 2100-2400 aa's. Both ends of the genome are modified, the 5' end by a covalently attached small, basic protein VPg (~23 AA's), the 3' end by polyadenylation. In a series of cleavages, viral proteases cleave themselves out and break down the polyprotein into 10 separate gene products involved in replication and packaging. 
The viral proteases 2A cleaves the p220 subunit of the cap binding complex (eIF4F subunit of eIF4G), making host cell mRNA unrecognizable to ribosomes. As a result, the 2A protease abrogates most of the host cell's own protein synthesis. Doing so increases the number of free ribosomes to translate viral RNA and insures that the cell will break down, releasing progeny viruses. Viral mRNA relies on a 5' UTR containing a 'clover-leaf' secondary known as an internal ribosome entry site (IRES) that serves as a ribosome docking site to the 40S subunit of ribosomes. 

Fundamental Virology,  p.482 
The 5' methyl-guanosine cap attached to host mRNA for ribosome recognition is unnecessary in poliovirus, allowing for viral RNA translation. The primary attenuating mutation in the Sabin vaccine is located  in the IRES. While Sabin poliovirus can replicate efficiently in gut epithelial tissues (primary site of replication), it is unable to replicate efficiently in the nervous system. 

RNA Replication 
Replication occurs entirely in the cytoplasm. In addition to serving as a template for protein synthesis, the positive sense strand genome is utilized as a template for the synthesis negative sense strands. Host cells lack the necessary machinery to replicate RNA. Poliovirus uses a viral RNA-dependent RNA polymerase to produce RNA molecules of the opposite polarity. Viral protein VPg covalently attached to uridine (VPg-UUU) serves as the primer. The first round of replication produces a single antisense molecule. This antisense template is then used to produce sense copies of the original genome that can be packaged into viral capsids prior to viral release. Antisense genomes can translated as well. 

Packaging and Release  
After the virus has translated its RNA to produce the necessary proteins and replicated its genome, it needs to package the newly synthesized RNA molecules inside capsids. A complete virus consists of the RNA packaged inside the capsid. The capsid proteins self-assemble into an immature capsid, a structure which contains all of the necessary proteins, but which has not finished cleaving them into their final form. The mature poliovirus capsid has icosahedral symmetry and contains 60 copies of each viral capsid protein (VP1,2,3,4) The viral RNA enters the incomplete capsid and is secured inside when the viral proteases make the final cleavages. Once the genomes have been packaged into mature virions, the virus particles await the cell's lysis in order to be released. As many as 100,000 virions can be released from a single infected cell. 

Binding between the virus and its receptor leads to conformational changes in the capsid. VP4, an internal capsid protein detaches from the capsid. The capsid swells and the poliovirus genome is susceptible to degradation. When VP1 is released, the genome is released onto the cytoplasm of the cell. The viral entry strategy is very inefficient; only 1% of the viruses initiate an infection. 

Time after Infection
~30 min
cellular protein synthesis declines sharply (SHUTOFF)
Sharp decrease in cellular macromolecular synthesis; margination of chromatin (loss of homogeneous appearance of nucleus)
Start of viral protein synthesis; vacuolation of cytoplasm, beginning close to nucleus & spreading outwards
Permeabilization of plasma membrane
Virus assembly in cytoplasm (crystals sometimes visible)
Cell lysis; release of virus particles
Scanning Electron Microscopy of surface alterations of HEp-2 cells 

A. Cells at 3 hours past infection. Rounding of cells and pyknosis.  
     Elongation of filopodia.  
B. Cells at 8 hours past infection. Rounding of cell. Elongation of filopodia.  
C. Colapse of Microvilli.  
D and E.. Cells at 10 hours past infection. Merging of filopodia occurs. 

Koch, The Molecular Biology of Poliovirus, p.231 




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  • Siendo que tenemos muy presente como Organización Civil nuestra dirección en representar a las personas que padecen de secuela de polio y a sus familias, a los que ya padecen del Síndrome de Post Polio (SPP)
  • Siendo que tenemos muy presente como Organización Civil nuestra dirección en representar a las personas que padecen de secuela de polio y a sus familias, a los que ya padecen del Síndrome de Post Polio (SPP)