Selective EMC subunits act as molecular tethers of intracellular organelles exploited during viral entry

Although viruses must navigate the complex host endomembrane system to infect cells, the strategies used to achieve this is unclear. During entry, polyomavirus SV40 is sorted from the late endosome (LE) to the endoplasmic reticulum (ER) to cause infection, yet how this is accomplished remains enigmatic. Here we find that EMC4 and EMC7, two ER membrane protein complex (EMC) subunits, support SV40 infection by promoting LE-to-ER targeting of the virus. They do this by engaging LE-associated Rab7, presumably to stabilize contact between the LE and ER. These EMC subunits also bind to the ER-resident fusion machinery component syntaxin18, which is required for SV40-arrival to the ER. Our data suggest that EMC4 and EMC7 act as molecular tethers, inter-connecting two intracellular compartments to enable efficient transport of a virus between these compartments. As LE-to-ER transport of cellular cargos is unclear, our results have broad implications for illuminating inter-organelle cargo transport.


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All experiments were replicated at least three times and all attempts of replication were successful.
GFP-expressing cells and scrambled siRNA-transfected cells were grouped as control. Cells expressing protein of interest (such as EMC4 or EMC7) and cells transfected with a siRNA against a protein of interest (such as EMC4 or EMC7) were grouped as test samples.
Under the microscope, GFP-expressing cells (control) is visually distinct from cells expressing the protein of interest (test) which are ER membrane proteins; for this reason, it is not possible to blind this experiment. In the knockdown studies, instead of blinding, data were confirmed independently by other investigators in the lab.