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. Author manuscript; available in PMC: 2021 Feb 12.
Published in final edited form as: Biochem Soc Trans. 2020 Oct 30;48(5):2173–2184. doi: 10.1042/BST20200395

Figure 2. The ER serves as a membrane penetration site during polyomavirus entry.

Figure 2.

Upon endocytosis, polyomavirus SV40 reaches the endosome. Two specific subunits of the ER membrane protein complex (EMC), EMC4 and EMC7, tether the ER to the endosome (step 1). This physical juxtaposition allows SV40 in the endosome to be efficiently delivered into the ER. In the ER, redox chaperones including PDI, ERp57, and ERdj5 reduce and isomerize disulfide bonds of SV40 (step 2), leading to exposure of the hydrophobic viral VP2 and VP3 proteins. This generates a hydrophobic particle that integrates into the ER membrane that primes the virus for ER escape into the cytosol (step 3). During ER-to-cytosol escape, SV40 creates a membrane penetration structure on the ER membrane called ‘focus’ (step 4); focus formation requires reorganization of select ER membrane proteins, including BAP31, RTN3/4, EMC1, and J proteins. The J proteins in turn recruit a cytosol extraction machinery composed of Hsc70, SGTA, and Hsp105/Bag2. This machinery, in conjunction with Ubiqln4, acts to extract the membrane-embedded SV40 into the cytosol (step 5). The cytosol-localized virus is disassembled by the BICD adaptors of the dynein motor complex, enabling the viral particle entry into the nucleus to cause infection.