1.A.83 The SV40 Virus Viroporin VP2 (SV40 VP2) Family

For nonenveloped viruses such as Simian Virus 40, the mechanism used to translocate viral components across membranes involves viroporins. The minor structural proteins, VP2 and VP3, which are products of the same gene and differ in that VP2 has 118 aas at the N-terminus that are lacking in VP3, apparently act as membrane proteins during infection. Giorda et al. (2012) purified VP2 and VP3, and both were found to form pores in host cell membranes. To identify possible membrane domains, individual hydrophobic domains from VP2 and VP3 were expressed in a model protein and tested for their ability to integrate into membranes. Several domains from the late proteins supported endoplasmic reticulum membrane insertion as transmembrane domains. Mutations in VP2 and VP3 were engineered that inhibited membrane insertion and pore formation. When these mutations were introduced into the viral genome, viral propagation was inhibited. Thus, the viroporin activities of VP2 and VP3 were inhibited by targeted disruptions of individual hydrophobic domains, and the loss of membrane disruption activity impaired viral infection (Giorda et al. 2012).


 

References:

Chen, X.S., T. Stehle, and S.C. Harrison. (1998). Interaction of polyomavirus internal protein VP2 with the major capsid protein VP1 and implications for participation of VP2 in viral entry. EMBO. J. 17: 3233-3240.

Giorda KM., Raghava S., Zhang MW. and Hebert DN. (2013). The viroporin activity of the minor structural proteins VP2 and VP3 is required for SV40 propagation. J Biol Chem. 288(4):2510-20.

Raghava, S., K.M. Giorda, F.B. Romano, A.P. Heuck, and D.N. Hebert. (2011). The SV40 late protein VP4 is a viroporin that forms pores to disrupt membranes for viral release. PLoS Pathog 7: e1002116.

Raghava, S., K.M. Giorda, F.B. Romano, A.P. Heuck, and D.N. Hebert. (2013). SV40 late protein VP4 forms toroidal pores to disrupt membranes for viral release. Biochemistry 52: 3939-3948.

Scott, C. and S. Griffin. (2015). Viroporins: structure, function and potential as antiviral targets. J Gen Virol 96: 2000-2027.

Examples:

TC#NameOrganismal TypeExample
1.A.83.1.1

Viroporin VP2

Viruses

VP2 of SV40 virus

 
1.A.83.1.2

SV40 VP4 viroporin protein of 125 aas and 1 TMS (Raghava et al. 2011).  It forms Ca2+-selective toroidal pores to disrupt membranes for viral particle release (Raghava et al. 2013; Scott and Griffin 2015).

VP4 of Simian Virus 40 (SV40)

 
1.A.83.1.3

VP2 protein of 240 aas and 1 TMS.

VP2 of Pan troglodytes verus polyomavirus 1a

 
1.A.83.1.4

VP3 protein of 190 aas and 1 TMS

VP3 of Chimpanzee polyomavirus

 
1.A.83.1.5

The structure of the polyomavirus internal protein including a synthetic fragment of 18 aas in which the C-terminal sequence is derived from Vp2 of 319 aas and a 283 aa fragment of the major capsid protein Vp1, which has a full length of 384 aas, is known (1CN3), providing insight into their involvement in viral entry (Chen et al. 1998). The fragments of Vp1 and Vp2, present in this complex, are derived by proteolysis from two large full length proteins, Vp1 and Vp2 as noted above. These full length proteins are included here under TC# 1.A.83.1.5. There are multiple structures reported in PDB of the Vp1 protein: 1CN3, 1SID, 1SIE, 1VPN, 1VPS, 5CPZ, 5CQ0.

Vp2 of polyomavirus

 
1.A.83.1.6

Minor capsid protein VP2/VP3 complex.  Isoforms VP2 and VP3 are structural proteins that reside within the core of the capsid surrounded by 72 VP1 pentamers. They participate in host cell receptor binding together with VP1, the major capsid protein. Following virus endocytosis and trafficking to the endoplasmic reticulum, VP2 and VP3 form oligomers and integrate into the endoplasmic reticulum membrane. Heterooligomer VP2-VP3 may create a viroporin for transporting the viral genome across the ER membrane to the cytoplasm. Nuclear entry of the viral DNA involves the selective exposure and importin recognition of a VP2 or Vp3 nuclear localization signal (shared C-terminus). hey play a role in virion assembly within the nucleus, in particular through a DNA-binding domain located in the C-terminal region. N-terminal myristoylation suggests a scaffold function for virion assembly.

VP2/VP3 of Budgerigar fledgling disease virus (BFPyV) (Aves polyomavirus 1)
VP2, 341 aas with 1 - 2 TMSs, P13892
VP3, 235 aas with 2 - 3 TMSs, D2KCA6