Immunoglobulin mimicry by Hepatitis C Virus envelope protein E2.
Hepatitis C virus (HCV) establishes persistent infection in the majority of infected individuals. The currently accepted hypothesis of immune evasion by antigenic variation in hypervariable region 1 (HVR1) of glycoprotein E2 does not however, explain the lack of subsequent immune recognition. Here, we show that the N-terminal region of E2 is antigenically and structurally similar to human immunoglobulin (Ig) variable domains. E2 is recognized by anti-human IgG antibodies and also possesses common amino acid (aa) sequence features of the conserved v-gene framework regions of human Ig light chains in particular but also heavy chains and T cell receptors. Using a position specific scoring system, the degree of similarity of HVR1 to Ig types correlated with immune escape and persistence in humans and experimentally infected chimpanzees. We propose a unique role for threshold levels of Ig molecular mimicry in HCV biology that not only advances our concept of viral immune escape and persistent infection but also provides insight into host-dependent disease patterns.
Hu
Yu-Wen
YW
Canadian Blood Services, 1800 Alta Vista Drive, Ottawa, Ontario, Canada K1G 4J5. yu-wen.hu@bloodservices.ca
Rocheleau
Lynda
L
Larke
Bryce
B
Chui
Linda
L
Lee
Bonita
B
Ma
Mang
M
Liu
Song
S
Omlin
Teye
T
Pelchat
Martin
M
Brown
Earl G
EG
D000595:Amino Acid Sequence; D004926:Escherichia coli; D005838:Genotype; D016174:Hepacivirus / Q000737:chemistry* / Q000276:immunology; D006526:Hepatitis C; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology; D014765:Viral Vaccines
D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines