1.P.1.  The Polyoma Virus SV40 ER Penetration Channel (VPEC) Family 

Non-enveloped polyoma virus SV40 penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol and cause infection. Inoue and Tsai 2017 demonstrated that SV40 creates its own membrane penetration structure by mobilizing host cell transmembrane proteins to distinct puncta in the ER membrane, called foci, that likely function as the cytosol entry sites.  The DnaJ homolog subfamily B, member 12, B12 (DnaJ-B12), is a transmembrane J-protein of 375 aas and 1 TMS that mobilizes into the foci to promote cytosolic entry of SV40. Inoue and Tsai 2017 identified two closely related ER membrane proteins, Erlin1 and Erlin2 (Erlin1/2) as B12-interaction partners. SV40 recruits B12 to the foci by inducing release of this J-protein from Erlin1/2. Thus, a non-enveloped virus promotes its own membrane translocation by triggering the release and recruitment of critical transport factors to the ER membrane.

Ravindran et al. 2017 probed how SV40 penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol. They found that the microtubule-based motor kinesin-1 is recruited to the ER membrane by binding to the transmembrane J-protein B14. Strikingly, this motor facilitates SV40 ER-to-cytosol transport by constructing a penetration site on the ER membrane called a 'focus'. Neither kinesin-2, kinesin-3 nor kinesin-5 promoted foci formation or infection. The specific use of kinesin-1 is due to its unique ability to select posttranslationally modified microtubules for cargo transport and thereby spatially restrict focus formation to the perinucleus. These findings support the idea of a 'tubulin code' for motor-dependent trafficking and establish a distinct kinesin-1 function in which a motor is exploited to create a viral membrane penetration site (Ravindran et al. 2017).



Inoue, T. and B. Tsai. (2017). Regulated Erlin-dependent release of the B12 transmembrane J-protein promotes ER membrane penetration of a non-enveloped virus. PLoS Pathog 13: e1006439. [Epub: Ahead of Print]

Ravindran, M.S., M.F. Engelke, K.J. Verhey, and B. Tsai. (2017). Exploiting the kinesin-1 molecular motor to generate a virus membrane penetration site. Nat Commun 8: 15496.


TC#NameOrganismal TypeExample

The SV40 ER membrane penitration complex involving the DnaJ-B12 protein of 375 aas and 1 TMS or the transmembrane J-protein B14 as well as Erlin1 (SPFH1; 346 aas and 1 TMS) and Erlin2 (SPFH2; 339 aas and 1 TMS) (Inoue and Tsai 2017). Kinesin-1 (KIF5B or KNS1) may serve as the motor (Ravindran et al. 2017).  See family description for details.

The SV40 penitration complex
DnaJ-B12 (Q9NXW2)
Erlin1 (O75477)
Erlin2 (O94905)
Transmembrane DnaJ-protein B14 (Q8TBM8)
Kinesin-1 (P33176)