SV40 – not finished yet

SV40 translocation Every year I treat the students on my virology course to a lengthy diatribe about how important SV40 has been to understanding so many different aspects of virology. How can such a small virus have made such a big impact? 55 years after its discovery, SV40 continues to surpise and illuminate us.

How non-enveloped viruses penetrate a host membrane to enter cells and cause disease remains enigmatic. To infect cells, the non-enveloped SV40 must transport itself across the ER membrane to reach the cytosol. A new study reveals some of the details of how it achieves that. Cellular Hsp105-powered disaggregation machinery pulls SV40 into the cytosol, most likely by uncoating the ER membrane-penetrating virus. Because this disaggregation machinery is thought to clear cellular aggregated proteins, the authors propose that the force generated by this machinery can also be hijacked by this non-enveloped virus to propel its entry into the host.

 

A Non-enveloped Virus Hijacks Host Disaggregation Machinery to Translocate across the Endoplasmic Reticulum Membrane. (2015) PLoS Pathog 11(8): e1005086. doi: 10.1371/journal.ppat.1005086
Mammalian cytosolic Hsp110 family, in concert with the Hsc70:J-protein complex, functions as a disaggregation machinery to rectify protein misfolding problems. Here we uncover a novel role of this machinery in driving membrane translocation during viral entry. The non-enveloped virus SV40 penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol, a critical infection step. Combining biochemical, cell-based, and imaging approaches, we find that the Hsp110 family member Hsp105 associates with the ER membrane J-protein B14. Here Hsp105 cooperates with Hsc70 and extracts the membrane-penetrating SV40 into the cytosol, potentially by disassembling the membrane-embedded virus. Hence the energy provided by the Hsc70-dependent Hsp105 disaggregation machinery can be harnessed to catalyze a membrane translocation event.

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One Response to SV40 – not finished yet

  1. Ed Rybicki says:

    Excellent! Love it how some of the old-style and new-style virology is yielding new insights.

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