Coxsackie B4 virus

The capsid of Coxsackie viruses have a distinguishable depression around the fivefold axis, termed the “canyon.” The canyon is thought to help with viral attachment through the interaction with cell surface molecules. (Riabi, 2014) When VP1 binds to the Coxsackie-Adenovirus receptor (CAR), which can be found on heart muscle cells as well as epithelial and endothelial cells,[3] a conformational change causes the host cell receptors to form a pore in the plasma membrane through which the VPg-linked viral genome could enter the cell.[2] Uncoating is unnecessary as it leaves the capsid at the plasma membrane and the genome is simply injected into the cytoplasm.

For positive sense, single-stranded RNA viruses, translation occurs before transcription. Upon entry of the genome into the cytoplasm of the host cell, the IRES in the 5’ UTR recruits ribosomal subunits (cap-independent mechanism) which starts the translation process. Once the polypeptide is completely translated, viral proteinases 2A and 3C, as well as cellular proteinases, cleave the polyprotein into individual proteins that will help continue the viral replication process.[4]

As soon as viral proteins have been translated and cleaved, negative sense transcripts of the viral genome are made to serve as a template for more positive-sense viral genome transcripts (which also serves as mRNA which can also be translated into more viral proteins). The viral genome encodes for a poly-A tail, which can be recognized by cellular initiation factors and ribosomal subunits which kick starts the transcription process to make the negative-sense strand, forming a double-stranded RNA intermediate[5]

Upon transcription of the negative sense RNA, it needs to get primed in order to start making more positive sense RNA genome. The VPg protein that is covalently linked to the 5’ end of the RNA genome has 2 U’s attached to it. The purpose of these U’s is to modify the VPg protein which serves as a protein primer which the viral RdRP can recognize and start forming more genome from the negative-sense.[5]

The viral protein 2C brings positive sense RNA genomes to the endoplasmic reticulum where assembly and maturation will occur.[4]

While all of this is occurring, viral proteinases are working to turn off host cell protein synthesis by cleaving the eIF-4 initiation factor. This process accomplishes the inhibition of ribosomes binding to host cell mRNAs. This effectively shuts down cap-dependent translation in the host cell.[4]

Once viral genome and viral proteins reach high enough concentrations within the host cell, structural proteins must assemble. The final step in maturation of the virus is when VP0, a precursor protein, is cleaved into VP2 and VP4. Viral capsid proteins come together to form pentamers, 12 of which come together to form an empty capsid, or procapsid (Expasy, Hunt, 2010). As mentioned before, the viral protein 2C brings CB4 viral genome to the endoplasmic reticulum where vesicle formation begins. The ER membrane moves to surround the genome and proteins, at which point the procapsid attaches to the exterior of the vesicle and encapsidates the genome and proteins. It is at this point that VP0 gets cleaved by a cellular proteinase and the virus finally becomes fully mature and infectious. Since CB4 is a non-enveloped virus, it accomplishes egress through cytolysis, breaking through the plasma membrane in order to move on to infect other cells in the host (Hunt, 2010)