Limited naturally occurring escape in broadly neutralizing antibody epitopes in hepatitis C glycoprotein E2 and constrained sequence usage in acute infection

Chaturaka Rodrigo, Melanie R. Walker, Preston Leung, Auda A. Eltahla, Jason Grebely, Gregory J. Dore, Tanya Applegate, Kimberly Page, Sunita Dwivedi, Julie Bruneau, Meghan D. Morris, Andrea L. Cox, William Osburn, Arthur Y. Kim, Janke Schinkel, Naglaa H. Shoukry, Georg M. Lauer, Lisa Maher, Margaret Hellard, Maria Prins & 3 others Fabio Luciani, Andrew R. Lloyd, Rowena A. Bull

Research output: Contribution to journalArticle

Abstract

Broadly neutralizing antibodies have been associated with spontaneous clearance of the hepatitis C infection as well as viral persistence by immune escape. Further study of neutralizing antibody epitopes is needed to unravel pathways of resistance to virus neutralization, and to identify conserved regions for vaccine design. All reported broadly neutralizing antibody (BNAb) epitopes in the HCV Envelope (E2) glycoprotein were identified. The critical contact residues of these epitopes were mapped onto the linear E2 sequence. All publicly available E2 sequences were then downloaded and the contact residues within the BNAb epitopes were assessed for the level of conservation, as well as the frequency of occurrence of experimentally-proven resistance mutations. Epitopes were also compared between two sequence datasets obtained from samples collected at well-defined time points from acute (< 180 days) and chronic (> 180 days) infections, to identify any significant differences in residue usage. The contact residues for all BNAbs were contained within 3 linear regions of the E2 protein sequence. An analysis of 1749 full length E2 sequences from public databases showed that only 10 out of 29 experimentally-proven resistance mutations were present at a frequency > 5%. Comparison of subtype 1a viral sequences obtained from samples collected during acute or chronic infection revealed significant differences at positions 610 and 655 with changes in residue (p < 0.05), and at position 422 (p < 0.001) with a significant difference in variability (entropy). The majority of experimentally-described escape variants do not occur frequently in nature. The observed differences between acute and chronically isolated sequences suggest constraints on residue usage early in infection.

Original languageEnglish (US)
Pages (from-to)88-96
Number of pages9
JournalInfection, Genetics and Evolution
Volume49
DOIs
StatePublished - Apr 1 2017

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Hepatitis C
Neutralizing Antibodies
Epitopes
Glycoproteins
Infection
epitopes
antibody
neutralizing antibodies
infection
Mutation
hepatitis
mutation
hepatitis C
glycoproteins
sampling
Entropy
Vaccines
Viruses
Proteins
Datasets

Keywords

  • Broadly neutralizing antibodies
  • Epitopes
  • Glycoprotein E2
  • Hepatitis C
  • InC collaborative

ASJC Scopus subject areas

  • Microbiology
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Limited naturally occurring escape in broadly neutralizing antibody epitopes in hepatitis C glycoprotein E2 and constrained sequence usage in acute infection. / Rodrigo, Chaturaka; Walker, Melanie R.; Leung, Preston; Eltahla, Auda A.; Grebely, Jason; Dore, Gregory J.; Applegate, Tanya; Page, Kimberly; Dwivedi, Sunita; Bruneau, Julie; Morris, Meghan D.; Cox, Andrea L.; Osburn, William; Kim, Arthur Y.; Schinkel, Janke; Shoukry, Naglaa H.; Lauer, Georg M.; Maher, Lisa; Hellard, Margaret; Prins, Maria; Luciani, Fabio; Lloyd, Andrew R.; Bull, Rowena A.

In: Infection, Genetics and Evolution, Vol. 49, 01.04.2017, p. 88-96.

Research output: Contribution to journalArticle

Rodrigo, C, Walker, MR, Leung, P, Eltahla, AA, Grebely, J, Dore, GJ, Applegate, T, Page, K, Dwivedi, S, Bruneau, J, Morris, MD, Cox, AL, Osburn, W, Kim, AY, Schinkel, J, Shoukry, NH, Lauer, GM, Maher, L, Hellard, M, Prins, M, Luciani, F, Lloyd, AR & Bull, RA 2017, 'Limited naturally occurring escape in broadly neutralizing antibody epitopes in hepatitis C glycoprotein E2 and constrained sequence usage in acute infection' Infection, Genetics and Evolution, vol 49, pp. 88-96. DOI: 10.1016/j.meegid.2017.01.006

Rodrigo, Chaturaka; Walker, Melanie R.; Leung, Preston; Eltahla, Auda A.; Grebely, Jason; Dore, Gregory J.; Applegate, Tanya; Page, Kimberly; Dwivedi, Sunita; Bruneau, Julie; Morris, Meghan D.; Cox, Andrea L.; Osburn, William; Kim, Arthur Y.; Schinkel, Janke; Shoukry, Naglaa H.; Lauer, Georg M.; Maher, Lisa; Hellard, Margaret; Prins, Maria; Luciani, Fabio; Lloyd, Andrew R.; Bull, Rowena A. / Limited naturally occurring escape in broadly neutralizing antibody epitopes in hepatitis C glycoprotein E2 and constrained sequence usage in acute infection.

In: Infection, Genetics and Evolution, Vol. 49, 01.04.2017, p. 88-96.

Research output: Contribution to journalArticle

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