Hepatitis C virus envelope glycoprotein E1

E1 is one of two subunits of the envelope glycoprotein[1] found in the hepatitis C virus.[2][3] The other subunit is E2. This protein is a type 1 transmembrane protein with a highly glycosylated N-terminal ectodomain and a C-terminal hydrophobic anchor. After being synthesized the E1 glycoproteins associates with the E2 glycoprotein as a noncovalent heterodimer.[4]

Structure

The E1 glycoprotein residues 192-383 in the genotype 1a H77 strain. After translation the E1 C-terminal transmembrane domains (TMDs) forms a hairpin of antiparallel a-helices. E1 is then cleaved by signal peptide peptidase at the endoplasmic reticulum and E1 is then made into a single long straight a-helix. What is known of the structure is from a crystal structure made in 2014.[5] This crystal structure shows that it has two a-helixes and 3 B-sheets for both monomers; two disulfide bridges stabilize these two monomers. This means that E1 is more compact then its E2 counterpart. It has been shown that E1 can fold with a small amount of E2 protein present. In addition to this it was shown that E1 oxidation preceded E2 maturation. This means that E1 has a chaperone-like role for E2.[6]

Function

The E1 protein helps the virus attach to the membrane of the targeted cell. In other envelope virus the E1 protein has a similar role in helping the virus get into the cell. As a heterodimer with E2 it has been discovered that it is essential for HCV entry.[7] When the heterodimer is formed the hepatitis C virus is then able to bind to the receptor of the cell. As a heterodimer the E1 protein alone with the E2 protein worked together to enter the cell. Also cleavage at the core-E1 junction is a prerequisite for SPP-catalyzed cleavage. This helps the virus relocate to the surface of lipid droplets. Once the virus gets to the surface of the lipid droplets it recruits the virus no-structural proteins and replication complex.[8]

Possible Vaccine

It has been shown that by blocking E1 we can prevent the formation of the envelope protein. There have been a number of studies trying to find the structure of E1. The hope for these vaccines is that they will be able to block the entry of Hepatitis C if they can block the formation of E1. If the virus cannot make the envelope protein then it will be unable to get into the host cells.[9] The types of vaccines that would be used are synthetic peptide vaccines.[10]

References

  1. ^ Haddad, J.G.; Rouille, Y.; et al. (2017). "Identification of Novel Functions for Hepatitis C virus Envelope Glycoprotein E1 in Virus Entry and Assembly". Journal of Virology. 91 (11) e00048-17. doi:10.1128/JVI.00048-17. PMC 5375667. PMID 28179528.
  2. ^ Garcia JE, Puentes A, Súarez J, et al. (February 2002). "Hepatitis C virus (HCV) E1 and E2 protein regions that specifically bind to HepG2 cells". J. Hepatol. 36 (2): 254–62. doi:10.1016/S0168-8278(01)00262-8. PMID 11830338.
  3. ^ Bartosch B, Dubuisson J, Cosset FL (March 2003). "Infectious Hepatitis C Virus Pseudo-particles Containing Functional E1–E2 Envelope Protein Complexes". J. Exp. Med. 197 (5): 633–42. doi:10.1084/jem.20021756. PMC 2193821. PMID 12615904.
  4. ^ Lavie, M.; Goffard, A.; Dubuisson, J. In Chapter 4 HCV Glycoproteins: Assembly of a Functional E1-E2 heterodimer; Norfolk: UK, 2006; .
  5. ^ Freedman, H.; Logan, M. R.; Law, J. L.; Houghton, M. (2016). "Structure and Function of the Hepatitis C Virus Envelope Glycoproteins E1 and E2: Antiviral and Vaccine Targets". ACS Infectious Diseases. 2 (11): 749–762. doi:10.1021/acsinfecdis.6b00110. PMID 27933781.
  6. ^ Abdelwahab, K. S.; Ahmed Said, Z. N. (2016). "Status of hepatitis C virus vaccination: Recent update". World Journal of Gastroenterology. 22 (2): 862–73. doi:10.3748/wjg.v22.i2.862. PMC 4716084. PMID 26811632.
  7. ^ Lavie, M.; Goffard, A.; Dubuisson, J. In Chapter 4 HCV Glycoproteins: Assembly of a Functional E1-E2 heterodimer; Norfolk: UK, 2006; .
  8. ^ Pène, V.; Lemasson, M.; Harper, F.; Pierron, G.; Rosenberg, A. R. (2017). "Role of cleavage at the core-E1 junction of hepatitis C virus polyprotein in viral morphogenesis". PLOS ONE. 12 (4) e0175810. Bibcode:2017PLoSO..1275810P. doi:10.1371/journal.pone.0175810. PMC 5402940. PMID 28437468.
  9. ^ Freedman, H.; Logan, M. R.; Law, J. L.; Houghton, M. (2016). "Structure and Function of the Hepatitis C Virus Envelope Glycoproteins E1 and E2: Antiviral and Vaccine Targets". ACS Infectious Diseases. 2 (11): 749–762. doi:10.1021/acsinfecdis.6b00110. PMID 27933781.
  10. ^ Abdelwahab, K. S.; Ahmed Said, Z. N. (2016). "Status of hepatitis C virus vaccination: Recent update". World Journal of Gastroenterology. 22 (2): 862–73. doi:10.3748/wjg.v22.i2.862. PMC 4716084. PMID 26811632.
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