Minor capsid proteins VP2 and VP3

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Minor capsid protein VP2
Identifiers
SymbolVP2
Pfam PF00761
InterPro IPR001070
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Minor capsid protein VP2 and minor capsid protein VP3 are viral proteins that are components of the polyomavirus capsid. Polyomavirus capsids are composed of three proteins; the major component is major capsid protein VP1, which self-assembles into pentamers that in turn self-assemble into enclosed icosahedral structures. The minor components are VP2 and VP3, which bind in the interior of the capsid. [1] [2] [3]

Contents

Gene expression

The circular genome of a representative polyomavirus, WU polyomavirus, with the late region at right indicating positions of the VP1, VP2, and VP3 genes. Gaynor plospathogens 2007 WUvirusgenome.png
The circular genome of a representative polyomavirus, WU polyomavirus, with the late region at right indicating positions of the VP1, VP2, and VP3 genes.

All three capsid proteins are expressed from alternative start sites on a single transcript of the "late region" of the circular viral chromosome (so named because it is transcribed late in the process of viral infection). The VP3 start site is in frame downstream from that of VP2; in consequence VP3's sequence is identical to the C-terminal portion of VP2, which has an additional N-terminal extension. [1] [2] In at least some polyomaviruses, the VP2 N-terminus is myristoylated. [1] [3] Some members of the polyomavirus family, such as Merkel cell polyomavirus, do not appear to encode or express VP3, though VP2 is present. [3] [5]

Structure and interactions

A fragment of the murine polyomavirus VP2 (yellow) in complex with the major capsid protein VP1 (blue). From PDB: 1CN3 . 1cn3 vp2.png
A fragment of the murine polyomavirus VP2 (yellow) in complex with the major capsid protein VP1 (blue). From PDB: 1CN3 ​.

Both VP2 and VP3 are primarily intrinsically unstructured proteins; they have DNA-binding domains [6] and a nuclear localization signal at their C-terminal ends. [7] Both VP2 and VP3 bind to the interior of VP1 pentamers in the assembled capsid. [1] [2] It is generally believed that the stoichiometry of this interaction is one molecule of VP2 or VP3 to each VP1 pentamer, [2] though higher ratios have sometimes been reported, possibly indicating that pentamers can accommodate associations with two minor proteins. [3]

Function

VP2 and VP3 are thought to be involved in facilitating viral entry into the host cell, either by mediating associations with and exit from the endoplasmic reticulum or by facilitating the entry of the viral genome into the cell nucleus. [7] [8] [9] [10] [11] However, the precise mechanism of their involvement is unclear, and may vary among polyomaviruses. In most studies, viral propagation is either reduced or abrogated in the absence of one or both proteins, but the apparent mechanisms vary; for example, in JC virus both VP2 and VP3 seem to be essential for packaging the viral chromosome into the capsid, [12] while absence of these proteins in SV40 prevents successful entry into new host cells, [8] [9] with variable effects on packaging reported. [8] [13] In Merkel cell polyomavirus, the effect of VP2 appears to vary depending on the cell type of the infected cell. [3] In murine polyomavirus the minor proteins have been reported to induce apoptosis in the infected cell, [14] and in SV40 they have been identified as viroporins. [15]

See also

Related Research Articles

<span class="mw-page-title-main">Poliovirus</span> Enterovirus

Poliovirus, the causative agent of polio, is a serotype of the species Enterovirus C, in the family of Picornaviridae. There are three poliovirus serotypes: types 1, 2, and 3.

<i>Polyomaviridae</i> Family of viruses

Polyomaviridae is a family of viruses whose natural hosts are primarily mammals and birds. As of 2020, there are six recognized genera and 117 species, five of which are unassigned to a genus. 14 species are known to infect humans, while others, such as Simian Virus 40, have been identified in humans to a lesser extent. Most of these viruses are very common and typically asymptomatic in most human populations studied. BK virus is associated with nephropathy in renal transplant and non-renal solid organ transplant patients, JC virus with progressive multifocal leukoencephalopathy, and Merkel cell virus with Merkel cell cancer.

SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40, a polyomavirus that is found in both monkeys and humans. Like other polyomaviruses, SV40 is a DNA virus that sometimes causes tumors in animals, but most often persists as a latent infection. SV40 has been widely studied as a model eukaryotic virus, leading to many early discoveries in eukaryotic DNA replication and transcription.

<i>Dependoparvovirus</i> Genus of viruses

Dependoparvovirus is a genus in the subfamily Parvovirinae of the virus family Parvoviridae; they are Group II viruses according to the Baltimore classification. Some dependoparvoviruses are also known as adeno-associated viruses because they cannot replicate productively in their host cell without the cell being coinfected by a helper virus such as an adenovirus, a herpesvirus, or a vaccinia virus.

Merkel cell polyomavirus was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called digital transcriptome subtraction. MCV is one of seven currently known human oncoviruses. It is suspected to cause the majority of cases of Merkel cell carcinoma, a rare but aggressive form of skin cancer. Approximately 80% of Merkel cell carcinoma (MCC) tumors have been found to be infected with MCV. MCV appears to be a common—if not universal—infection of older children and adults. It is found in respiratory secretions, suggesting that it might be transmitted via a respiratory route. However, it has also been found elsewhere, such as in shedded healthy skin and gastrointestinal tract tissues, thus its precise mode of transmission remains unknown. In addition, recent studies suggest that this virus may latently infect the human sera and peripheral blood mononuclear cells.

<span class="mw-page-title-main">Late protein</span>

A late protein is a viral protein that is formed after replication of the virus. One example is VP4 from simian virus 40 (SV40).

Trichodysplasia spinulosa polyomavirus is a member virus of Human polyomavirus 8 that infects human hosts. First discovered in 2010, TSPyV is associated with Trichodysplasia spinulosa, a rare skin disease only seen in immunocompromised patients. The virus causes hyperproliferation and enlargement of hair follicles by modulating PP2A protein phosphatase signaling pathways. TSPyV was the eighth human polyomavirus to be discovered, and one of four associated with human disease, out of 13 human polyomaviruses known as of the 2015 update to polyomavirus taxonomy released by the International Committee on Taxonomy of Viruses.

<span class="mw-page-title-main">Murine polyomavirus</span> Species of virus

Murine polyomavirus is an unenveloped double-stranded DNA virus of the polyomavirus family. The first member of the family discovered, it was originally identified by accident in the 1950s. A component of mouse leukemia extract capable of causing tumors, particularly in the parotid gland, in newborn mice was reported by Ludwik Gross in 1953 and identified as a virus by Sarah Stewart and Bernice Eddy at the National Cancer Institute, after whom it was once called "SE polyoma". Stewart and Eddy would go on to study related polyomaviruses such as SV40 that infect primates, including humans. These discoveries were widely reported at the time and formed the early stages of understanding of oncoviruses.

<span class="mw-page-title-main">Minute virus of mice</span> Virus

Minute virus of mice (MVM) is the exemplar virus of the species Rodent protoparvovirus 1, in the genus Protoparvovirus of the Parvoviridae family of viruses. MVM exists in multiple variant forms including MVMp, which is the prototype strain that infects cells of fibroblast origin, while MVMi, the immunosuppressive strain, infects T lymphocytes. MVM is a common infection in laboratory mice due to its highly contagious nature. The virus can be shed from infected mice via feces and urine, but also via fomites and nasal secretions. Typically there are no clinical signs of infection in adult mice, however, experimental infection can cause multiple organ damage during fetal development or shortly after birth.

<span class="mw-page-title-main">Major capsid protein VP1</span>

Major capsid protein VP1 is a viral protein that is the main component of the polyomavirus capsid. VP1 monomers are generally around 350 amino acids long and are capable of self-assembly into an icosahedral structure consisting of 360 VP1 molecules organized into 72 pentamers. VP1 molecules possess a surface binding site that interacts with sialic acids attached to glycans, including some gangliosides, on the surfaces of cells to initiate the process of viral infection. The VP1 protein, along with capsid components VP2 and VP3, is expressed from the "late region" of the circular viral genome.

Hamster polyomavirus is an unenveloped double-stranded DNA virus of the polyomavirus family whose natural host is the hamster. It was originally described in 1967 by Arnold Graffi as a cause of epithelioma in Syrian hamsters.

WU polyomavirus is a virus of the family Polyomaviridae. It was discovered in 2007 in samples of human respiratory secretions, originally from a child patient in Australia who presented with clinical signs of pneumonia and in whom other common respiratory viruses were not detected. Follow-up studies identified the presence of WU virus in respiratory secretion samples from patients in Australia and the United States, suggesting that, like other human polyomaviruses, WU virus is widely distributed.

KI polyomavirus is a virus of the family Polyomaviridae. It was discovered in 2007 in stored samples of human respiratory secretions collected by the Karolinska Institute, after which the virus is named.

<span class="mw-page-title-main">Agnoprotein</span> Viral protein found in some polyomaviruses

Agnoprotein is a protein expressed by some members of the polyomavirus family from a gene called the agnogene. Polyomaviruses in which it occurs include two human polyomaviruses associated with disease, BK virus and JC virus, as well as the simian polyomavirus SV40.

MW polyomavirus is a virus of the polyomavirus family that infects human hosts. It was discovered in 2012 and reported independently by several research groups. It has been identified mostly in stool samples from children and has been detected in a variety of geographic locations.

STL polyomavirus is a virus of the polyomavirus family that infects human hosts. It was first reported in 2013 and is most closely related to MW polyomavirus. It has been identified mostly in stool samples from children and has been detected in a variety of geographic locations.

New Jersey polyomavirus is a virus of the polyomavirus family that infects human hosts. It was first identified in 2014 in a pancreatic transplant patient in New Jersey. It is the 13th and most recent human polyomavirus to be described.

<span class="mw-page-title-main">Large tumor antigen</span>

The large tumor antigen is a protein encoded in the genomes of polyomaviruses, which are small double-stranded DNA viruses. LTag is expressed early in the infectious cycle and is essential for viral proliferation. Containing four well-conserved protein domains as well as several intrinsically disordered regions, LTag is a fairly large multifunctional protein; in most polyomaviruses, it ranges from around 600-800 amino acids in length. LTag has two primary functions, both related to replication of the viral genome: it unwinds the virus's DNA to prepare it for replication, and it interacts with proteins in the host cell to dysregulate the cell cycle so that the host's DNA replication machinery can be used to replicate the virus's genome. Some polyomavirus LTag proteins - most notably the well-studied SV40 large tumor antigen from the SV40 virus - are oncoproteins that can induce neoplastic transformation in the host cell.

<span class="mw-page-title-main">Small tumor antigen</span>

The small tumor antigen is a protein encoded in the genomes of polyomaviruses, which are small double-stranded DNA viruses. STag is expressed early in the infectious cycle and is usually not essential for viral proliferation, though in most polyomaviruses it does improve replication efficiency. The STag protein is expressed from a gene that overlaps the large tumor antigen (LTag) such that the two proteins share an N-terminal DnaJ-like domain but have distinct C-terminal regions. STag is known to interact with host cell proteins, most notably protein phosphatase 2A (PP2A), and may activate the expression of cellular proteins associated with the cell cycle transition to S phase. In some polyomaviruses - such as the well-studied SV40, which natively infects monkeys - STag is unable to induce neoplastic transformation in the host cell on its own, but its presence may increase the transforming efficiency of LTag. In other polyomaviruses, such as Merkel cell polyomavirus, which causes Merkel cell carcinoma in humans, STag appears to be important for replication and to be an oncoprotein in its own right.

The middle tumor antigen is a protein encoded in the genomes of some polyomaviruses, which are small double-stranded DNA viruses. MTag is expressed early in the infectious cycle along with two other related proteins, the small tumor antigen and large tumor antigen. MTag occurs only in a few known polyomaviruses, while STag and LTag are universal - it was first identified in mouse polyomavirus (MPyV), the first polyomavirus discovered, and also occurs in hamster polyomavirus. In MPyV, MTag is an efficient oncoprotein that can be sufficient to induce neoplastic transformation in some cells.

References

  1. 1 2 3 4 5 Chen XS, Stehle T, Harrison SC (June 1998). "Interaction of polyomavirus internal protein VP2 with the major capsid protein VP1 and implications for participation of VP2 in viral entry". The EMBO Journal. 17 (12): 3233–40. doi:10.1093/emboj/17.12.3233. PMC   1170661 . PMID   9628860.
  2. 1 2 3 4 DeCaprio JA, Garcea RL (April 2013). "A cornucopia of human polyomaviruses". Nature Reviews. Microbiology. 11 (4): 264–76. doi:10.1038/nrmicro2992. PMC   3928796 . PMID   23474680.
  3. 1 2 3 4 5 Schowalter RM, Buck CB (2013-08-22). "The Merkel cell polyomavirus minor capsid protein". PLOS Pathogens. 9 (8): e1003558. doi: 10.1371/journal.ppat.1003558 . PMC   3749969 . PMID   23990782.
  4. ↑ Gaynor AM, Nissen MD, Whiley DM, Mackay IM, Lambert SB, Wu G, Brennan DC, Storch GA, Sloots TP, Wang D (May 2007). "Identification of a novel polyomavirus from patients with acute respiratory tract infections". PLOS Pathogens. 3 (5): e64. doi: 10.1371/journal.ppat.0030064 . PMC   1864993 . PMID   17480120.
  5. ↑ Buck CB, Van Doorslaer K, Peretti A, Geoghegan EM, Tisza MJ, An P, et al. (April 2016). "The Ancient Evolutionary History of Polyomaviruses". PLOS Pathogens. 12 (4): e1005574. doi: 10.1371/journal.ppat.1005574 . PMC   4836724 . PMID   27093155.
  6. ↑ Clever J, Dean DA, Kasamatsu H (October 1993). "Identification of a DNA binding domain in simian virus 40 capsid proteins Vp2 and Vp3". The Journal of Biological Chemistry. 268 (28): 20877–83. doi: 10.1016/S0021-9258(19)36868-1 . PMID   8407920.
  7. 1 2 Bennett SM, Zhao L, Bosard C, Imperiale MJ (January 2015). "Role of a nuclear localization signal on the minor capsid proteins VP2 and VP3 in BKPyV nuclear entry". Virology. 474: 110–6. doi:10.1016/j.virol.2014.10.013. PMC   4259852 . PMID   25463609.
  8. 1 2 3 Daniels R, Rusan NM, Wadsworth P, Hebert DN (December 2006). "SV40 VP2 and VP3 insertion into ER membranes is controlled by the capsid protein VP1: implications for DNA translocation out of the ER". Molecular Cell. 24 (6): 955–66. doi: 10.1016/j.molcel.2006.11.001 . PMID   17189196.
  9. 1 2 Nakanishi A, Itoh N, Li PP, Handa H, Liddington RC, Kasamatsu H (April 2007). "Minor capsid proteins of simian virus 40 are dispensable for nucleocapsid assembly and cell entry but are required for nuclear entry of the viral genome". Journal of Virology. 81 (8): 3778–85. doi:10.1128/jvi.02664-06. PMC   1866110 . PMID   17267496.
  10. ↑ Inoue T, Tsai B (May 2011). "A large and intact viral particle penetrates the endoplasmic reticulum membrane to reach the cytosol". PLOS Pathogens. 7 (5): e1002037. doi: 10.1371/journal.ppat.1002037 . PMC   3093372 . PMID   21589906.
  11. ↑ Huérfano S, Ryabchenko B, Španielová H, Forstová J (March 2017). "Hydrophobic domains of mouse polyomavirus minor capsid proteins promote membrane association and virus exit from the ER". The FEBS Journal. 284 (6): 883–902. doi: 10.1111/febs.14033 . PMID   28164464.
  12. ↑ Gasparovic ML, Gee GV, Atwood WJ (November 2006). "JC virus minor capsid proteins Vp2 and Vp3 are essential for virus propagation". Journal of Virology. 80 (21): 10858–61. doi:10.1128/jvi.01298-06. PMC   1641775 . PMID   17041227.
  13. ↑ Kawano MA, Inoue T, Tsukamoto H, Takaya T, Enomoto T, Takahashi RU, et al. (April 2006). "The VP2/VP3 minor capsid protein of simian virus 40 promotes the in vitro assembly of the major capsid protein VP1 into particles". The Journal of Biological Chemistry. 281 (15): 10164–73. doi: 10.1074/jbc.M511261200 . PMID   16478732.
  14. ↑ Huerfano S, Zíla V, Boura E, Spanielová H, Stokrová J, Forstová J (March 2010). "Minor capsid proteins of mouse polyomavirus are inducers of apoptosis when produced individually but are only moderate contributors to cell death during the late phase of viral infection". The FEBS Journal. 277 (5): 1270–83. doi: 10.1111/j.1742-4658.2010.07558.x . PMID   20121946.
  15. ↑ Giorda KM, Raghava S, Zhang MW, Hebert DN (January 2013). "The viroporin activity of the minor structural proteins VP2 and VP3 is required for SV40 propagation". The Journal of Biological Chemistry. 288 (4): 2510–20. doi: 10.1074/jbc.M112.428425 . PMC   3554919 . PMID   23223228.
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