Antigenic epitopes of the hepatitis A virus polyprotein.
Forty-two antigenic domains were identified across the hepatitis A virus (HAV) polyprotein by using a set of 237 overlapping 20-mer synthetic peptides spanning the entire HAV polyprotein and a panel of serum samples from acutely HAV-infected patients. The term "antigenic domain" is used in this study to define a protein region spanned with consecutive overlapping immunoreactive peptides. Nineteen antigenic domains were found within the structural proteins, and 22 were found within the nonstructural proteins, with 1 domain spanning the junction of VP1 and P2A proteins. Five of these domains were considered immunodominant, as judged by both the breadth and the strength of their immunoreactivity. One domain is located within the VP2 protein at position 57-90 aa. A second domain, located at position 767-842 aa, contains the C-terminal part of the VP1 protein and the entire P2A protein. A third domain, located at position 1403-1456 aa, comprises the C-terminal part of the P2C protein and the N-terminal half of the P3A protein. The fourth domain, located at position 1500-1519 aa, includes almost the entire P3B, and the last domain, located at position 1719-1764 aa, contains the C-terminal region of the P3C protein and the N-terminal region of the P3D protein. It is interesting to note that four of the five most immunoreactive domains are derived from small HAV proteins and/or encompass protein cleavage sites separating different HAV proteins. The HAV-specific immunoreactivity of each antigenically reactive peptide was confirmed by using seven HAV seroconversion panels. Collectively, these data demonstrate that HAV structural and nonstructural proteins contain antigenic epitopes that can be efficiently modeled with short synthetic peptides.
Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia, 30333, USA. yek0@cdc.gov
Y E
YE
Khudyakov
E N
EN
Lopareva
D L
DL
Jue
S
S
Fang
J
J
Spelbring
K
K
Krawczynski
H S
HS
Margolis
H A
HA
Fields
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D006506:Hepatitis A / Q000175:diagnosis / Q000276:immunology; D006507:Hepatovirus / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*; D015678:Viral Structural Proteins / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D007106:Immune Sera; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010446:Peptide Fragments; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D015678:Viral Structural Proteins