Representation of the early events involved in JCV infection. Representation of the early events involved in JCV infection. JCV (indicated by green viral capsids with supercoiled circular DNA) initially binds to carbohydrate receptors (likely α2,6-linked sialic acid) on the cell surface. The sialic acid could be attached to the G-protein-coupled 7-transmembrane receptor for serotonin (5HT2AR) or to another cell surface glycoprotein or glycolipid. The virus is then internalized into clathrin-coated pits and sorted into the early endosome. JCV colocalizes with cholera toxin, most likely in maturing or late endosomes. The virus then traffics to the to the ER by analogy with other polyomaviruses. It is likely that JCV interacts with PDI and ERAD proteins similar to those that interact with SV40 and mPyV in the ER. This is expected to cause conformational changes to the JCV virion, denoted by red shading of the capsid, and retrotranslocation of the virion into the cytoplasm. From there, it is likely that JCV enters the nucleus through the nuclear pore. Michael W. Ferenczy et al. Clin. Microbiol. Rev. 2012; doi:10.1128/CMR.05031-11