Virology

Come In and Take Your Coat Off

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Science  16 Nov 2007:
Vol. 318, Issue 5853, pp. 1039
DOI: 10.1126/science.318.5853.1039d

The replication of animal viruses relies on their ability to cross a cellular membrane on their way into the host cell's cytoplasm. Simian virus 40 (SV40) is a non-enveloped DNA virus that enters cells via caveolar endocytosis, followed by vesicular transport to the endoplasmic reticulum (ER)-the entry portal of the host cell's secretory pathway-whence it crosses into the cytosol en route to the nucleus. Schelhaas et al. wondered why the viruses follow this relatively complex itinerary. They found that ER-localized enzymes that promote the isomerization of cysteines between their thiol and disulfide states were required for viral entry, and that two ER membrane proteins, Derlin-1 and Sel1L, which are known to mediate the retrotranslocation of misfolded host proteins from the ER back into the cytoplasm, were also important. Specifically, the oxidoreductase ERp57 catalyzed a rearrangement of disulfides within the capsid, resulting in a loosening of the pentamer-hexamer joints in the virus coat. Once in the cytosol, the reduced levels of calcium may promote viral capsid disassembly, facilitating release of the genome. — SMH

Cell 131, 495 (2007).

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