VP40

Last updated
VP40
4ldd.jpg
VP40 matrix protein hexamer, Ebola virus
Identifiers
SymbolVP40
Pfam PF07447
InterPro IPR008986
SCOP2 1h2c / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

In molecular biology, VP40 is the name of a viral matrix protein. Most commonly it is found in the Ebola virus (EBOV), [1] a type of non-segmented, negative-strand RNA virus. Ebola virus causes a severe and often fatal haemorrhagic fever in humans, known as Ebola virus disease. The virus matrix protein VP40 is a major structural protein that plays a central role in virus assembly and budding at the plasma membrane of infected cells. VP40 proteins work by associating with cellular membranes, interacting with the cytoplasmic tails of glycoproteins and binding to the ribonucleoprotein complex.[ citation needed ]

Contents

Structure

The VP40 monomer consists of two protein domains, the N-terminal oligomerization domain and the C-terminal membrane-binding domain, connected by a flexible linker. Both the N- and C-terminal domains fold into beta sandwich structures of similar topology. [2] Within the N-terminal domain are two overlapping L-domains with the sequences PTAP and PPEY at residues 7 to 13, which are required for efficient budding. [3] L-domains are thought to mediate their function in budding through their interaction with specific host cellular proteins, such as TSG101 and vps-4. [4]

Function

Different structures VP40 assumes in its functional roles 178-EbolaVirusProteins VP40.png
Different structures VP40 assumes in its functional roles

VP40 coordinates numerous functions in the viral life cycle of the Ebola virus. These include: regulation of viral transcription, morphogenesis, packaging and budding of mature virions. [5]

VP40 goes through intermediate states of assembly (e.g. octamers). It has been noted that proteins encoded by EBOV (VP30, VP35, and VP40) act independently as suppressors of RNA silencing, indicating that the virus actively resists cellular RNAi during replication. [5]

Significance of VP40

VP40 position in the Ebola virus genome Genomul.png
VP40 position in the Ebola virus genome

Study of the matrix protein VP40 is important due to the high mortality rate of the Ebola virus, which is listed as a WHO Risk Group 4 Pathogen, an HHS Select Agent, an NIH/NIAID Category A Priority Pathogen, a CDC Category A Bioterrorism Agent, and a Biological Agent for Export Control by the Australia Group. [5]

Expression of the matrix protein VP40 is sufficient to generate virus-like particles (no viral genetic material) in a mammalian host that are remarkably indistinguishable from live virus, from a morphological standpoint. [5]

West African Ebola virus outbreak

During and after the 2014-2016 West African Ebola virus epidemic treatment options were sought; among them were the VP40 matrix protein as a target for possible research that may (or may not) lead to a therapeutic option. [6] [7]

Related Research Articles

<i>Filoviridae</i> Family of viruses in the order Mononegavirales

Filoviridae is a family of single-stranded negative-sense RNA viruses in the order Mononegavirales. Two members of the family that are commonly known are Ebola virus and Marburg virus. Both viruses, and some of their lesser known relatives, cause severe disease in humans and nonhuman primates in the form of viral hemorrhagic fevers.

<i>Ebolavirus</i> Genus of virus

The genus Ebolavirus is a virological taxon included in the family Filoviridae, order Mononegavirales. The members of this genus are called ebolaviruses, and encode their genome in the form of single-stranded negative-sense RNA. The six known virus species are named for the region where each was originally identified: Bundibugyo ebolavirus, Reston ebolavirus, Sudan ebolavirus, Taï Forest ebolavirus, Zaire ebolavirus, and Bombali ebolavirus. The last is the most recent species to be named and was isolated from Angolan free-tailed bats in Sierra Leone. Each species of the genus Ebolavirus has one member virus, and four of these cause Ebola virus disease (EVD) in humans, a type of hemorrhagic fever having a very high case fatality rate. The Reston virus has caused EVD in other primates. Zaire ebolavirus has the highest mortality rate of the ebolaviruses and is responsible for the largest number of outbreaks of the six known species of the genus, including the 1976 Zaire outbreak and the outbreak with the most deaths (2014).

<span class="mw-page-title-main">M1 protein</span>

The M1 protein is a matrix protein of the influenza virus. It forms a coat inside the viral envelope. This is a bifunctional membrane/RNA-binding protein that mediates the encapsidation of nucleoprotein cores into the membrane envelope. It is therefore required that M1 binds both membrane and RNA simultaneously.

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Membrane fusion proteins are proteins that cause fusion of biological membranes. Membrane fusion is critical for many biological processes, especially in eukaryotic development and viral entry. Fusion proteins can originate from genes encoded by infectious enveloped viruses, ancient retroviruses integrated into the host genome, or solely by the host genome. Post-transcriptional modifications made to the fusion proteins by the host, namely addition and modification of glycans and acetyl groups, can drastically affect fusogenicity.

<span class="mw-page-title-main">TSG101</span>

Tumor susceptibility gene 101, also known as TSG101, is a human gene that encodes for a cellular protein of the same name.

<span class="mw-page-title-main">CREB3</span> Protein-coding gene in the species Homo sapiens

Cyclic AMP-responsive element-binding protein 3 is a protein that in humans is encoded by the CREB3 gene.

<span class="mw-page-title-main">Tetherin</span> Mammalian protein found in Homo sapiens

Tetherin, also known as bone marrow stromal antigen 2, is a lipid raft associated protein that in humans is encoded by the BST2 gene. In addition, tetherin has been designated as CD317. This protein is constitutively expressed in mature B cells, plasma cells and plasmacytoid dendritic cells, and in many other cells, it is only expressed as a response to stimuli from IFN pathway.

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The species Taï Forest ebolavirus is a virological taxon included in the genus Ebolavirus, family Filoviridae, order Mononegavirales. The species has a single virus member, Taï Forest virus (TAFV). The members of the species are called Taï Forest ebolaviruses.

The species Sudan ebolavirus is a virological taxon included in the genus Ebolavirus, family Filoviridae, order Mononegavirales. The species has a single virus member, Sudan virus (SUDV). The members of the species are called Sudan ebolaviruses. It was discovered in 1977 and causes Ebola clinically indistinguishable from the ebola Zaire strain, but is less transmissible than it. Unlike with ebola Zaire there is no vaccine available.

<span class="mw-page-title-main">Marburg virus</span> Species of filamentous virus responsible for hemorrhagic fever

Marburg virus is a hemorrhagic fever virus of the Filoviridae family of viruses and a member of the species Marburg marburgvirus, genus Marburgvirus. Marburg virus (MARV) causes Marburg virus disease in primates, a form of viral hemorrhagic fever. The virus is considered to be extremely dangerous. The World Health Organization (WHO) rates it as a Risk Group 4 Pathogen. In the United States, the NIH/National Institute of Allergy and Infectious Diseases ranks it as a Category A Priority Pathogen and the Centers for Disease Control and Prevention lists it as a Category A Bioterrorism Agent. It is also listed as a biological agent for export control by the Australia Group.

<span class="mw-page-title-main">Vesiculovirus matrix proteins</span>

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<span class="mw-page-title-main">Ebola</span> Viral hemorrhagic fever of humans and other primates caused by ebolaviruses

Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses. Symptoms typically start anywhere between two days and three weeks after becoming infected with the virus. The first symptoms are usually fever, sore throat, muscle pain, and headaches. These are usually followed by vomiting, diarrhoea, rash and decreased liver and kidney function, at which point, some people begin to bleed both internally and externally. The disease kills between 25% and 90% of those infected – about 50% on average. Death is often due to shock from fluid loss, and typically occurs between six and 16 days after the first symptoms appear. Early treatment of symptoms increases the survival rate considerably compared to late start.

<i>Zaire ebolavirus</i> Species of virus affecting humans and animals

Zaire ebolavirus, more commonly known as Ebola virus, is one of six known species within the genus Ebolavirus. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal hemorrhagic fever in humans and other mammals, known as Ebola virus disease (EVD). Ebola virus has caused the majority of human deaths from EVD, and was the cause of the 2013–2016 epidemic in western Africa, which resulted in at least 28,646 suspected cases and 11,323 confirmed deaths.

Ebola viral protein 24 (eVP24) is considered a multifunctional secondary matrix protein present in viral particles. The broad roles eVP24 performs involve the formation of fully functional and infectious viral particles, promotion of filamentous nucleocapsid formation, mediation of host responses to infection, and suppression of the host innate immune system. It has been noted that eVP24 function can overlap with that of two other viral proteins; eVP40 matrix protein which functions in virus budding, and eVP35 which is also associated with immune suppression.

Bovine foamy virus (BFV) is a ss(+)RNA retrovirus that belongs to the genus spumaviridae. Spumaviruses differ from the other six members of family retroviridae, both structurally and in pathogenic nature. Spumaviruses derive their name from spuma the latin for "foam". The 'foam' aspect of 'foamy virus' comes from syncytium formation and the rapid vacuolization of infected cells, creating a 'foamy' appearance.

<span class="mw-page-title-main">Fadila Bouamr</span> French-American virologist

Fadila Bouamr is a French-American virologist researching the molecular mechanisms that govern the assembly and egress of an infectious HIV-1 and the proteins involved in these processes. She is chief of the viral budding unit at the National Institute of Allergy and Infectious Diseases.

References

  1. Dessen, Andréa; Volchkov, Viktor; Dolnik, Olga; Klenk, Hans-Dieter; Weissenhorn, Winfried (2000-08-15). "Crystal structure of the matrix protein VP40 from Ebola virus". The EMBO Journal. 19 (16): 4228–4236. doi:10.1093/emboj/19.16.4228. ISSN   0261-4189. PMC   302032 . PMID   10944105.
  2. Dessen A, Volchkov V, Dolnik O, Klenk HD, Weissenhorn W (August 2000). "Crystal structure of the matrix protein VP40 from Ebola virus". EMBO J. 19 (16): 4228–36. doi:10.1093/emboj/19.16.4228. PMC   302032 . PMID   10944105.
  3. Timmins J, Schoehn G, Ricard-Blum S, Scianimanico S, Vernet T, Ruigrok RW, Weissenhorn W (February 2003). "Ebola virus matrix protein VP40 interaction with human cellular factors Tsg101 and Nedd4". J. Mol. Biol. 326 (2): 493–502. doi:10.1016/S0022-2836(02)01406-7. PMID   12559917.
  4. Licata JM, Simpson-Holley M, Wright NT, Han Z, Paragas J, Harty RN (February 2003). "Overlapping motifs (PTAP and PPEY) within the Ebola virus VP40 protein function independently as late budding domains: involvement of host proteins TSG101 and VPS-4". J. Virol. 77 (3): 1812–9. doi:10.1128/jvi.77.3.1812-1819.2003. PMC   140960 . PMID   12525615.
  5. 1 2 3 4 Silva LP, Vanzile M, Bavari S, Aman JM, Schriemer DC (2012). "Assembly of Ebola Virus Matrix Protein VP40 Is Regulated by Latch-Like Properties of N and C Terminal Tails". PLOS ONE. 7 (7): e39978. Bibcode:2012PLoSO...739978S. doi: 10.1371/journal.pone.0039978 . PMC   3390324 . PMID   22792204.
  6. Madara, Jonathan J; Han, Ziying; Ruthel, Gordon; Freedman, Bruce D; Harty, Ronald N (2017-02-05). "The multifunctional Ebola virus VP40 matrix protein is a promising therapeutic target". Future Virology. 10 (5): 537–546. doi:10.2217/fvl.15.6. ISSN   1746-0794. PMC   4480923 . PMID   26120351.
  7. Balmith, Marissa; Soliman, Mahmoud E. S. (2017-02-01). "VP40 of the Ebola Virus as a Target for EboV Therapy: Comprehensive Conformational and Inhibitor Binding Landscape from Accelerated Molecular Dynamics". Cell Biochemistry and Biophysics . 75 (1): 65–78. doi:10.1007/s12013-017-0783-8. ISSN   1559-0283. PMID   28144904. S2CID   26535324.subscription needed
This article incorporates text from the public domain Pfam and InterPro: IPR008986