Immunologic evidence for lack of heterologous protection following resolution of HCV in patients with non-genotype 1 infection.

TY - JOUR

T1 - Immunologic evidence for lack of heterologous protection following resolution of HCV in patients with non-genotype 1 infection.

AU - Julian, Schulze Zur Wiesch

AU - Lauer, Georg M

AU - Timm, Joerg

AU - Kuntzen, Thomas

AU - Neukamm, Martin

AU - Berical, Andrew

AU - Jones, Andrea M

AU - Nolan, Brian E

AU - Longworth, Steve A

AU - Kasprowicz, Victoria

AU - McMahon, Cory

AU - Wurcel, Alysse

AU - Lohse, Ansgar W.

AU - Lewis-Ximenez, Lia L

AU - Chung, Raymond T

AU - Kim, Arthur Y

AU - Allen, Todd M

AU - Walker, Bruce D

PY - 2007

Y1 - 2007

N2 - Chronic hepatitis C virus (HCV) infection is typically characterized by a lack of virus-specific CD4(+) T-cell-proliferative responses, but strong responses have been described in a subset of persons with persistent viremia. One possible explanation for these responses is that they were primed by an earlier resolved infection and do not recognize the current circulating virus. We defined all targeted epitopes using overlapping peptides corresponding to a genotype 1a strain in 44 patients chronically infected with different HCV genotypes (GT). Surprisingly, more HCV-specific CD4(+) T-cell responses were detected in patients with chronic non-GT1 infection compared with patients with chronic GT1 infection (P = .017). Notably, we found serologic evidence of a previous exposure to GT1 in 4 patients with non-GT1 infection, and these persons also demonstrated significantly more responses than non-GT1 patients in whom genotype and HCV serotype were identical (P <.001). Comparison of recognition of GT1-specific peptides to peptides representing autologous virus revealed the absence of cross-recognition of the autologous circulating virus. These data indicate that persistent HCV infection can occur in the presence of an HCV-specific T-cell response primed against a heterologous HCV strain, and suggest that clearance of 1 GT does not necessarily protect against subsequent exposure to a second GT.

AB - Chronic hepatitis C virus (HCV) infection is typically characterized by a lack of virus-specific CD4(+) T-cell-proliferative responses, but strong responses have been described in a subset of persons with persistent viremia. One possible explanation for these responses is that they were primed by an earlier resolved infection and do not recognize the current circulating virus. We defined all targeted epitopes using overlapping peptides corresponding to a genotype 1a strain in 44 patients chronically infected with different HCV genotypes (GT). Surprisingly, more HCV-specific CD4(+) T-cell responses were detected in patients with chronic non-GT1 infection compared with patients with chronic GT1 infection (P = .017). Notably, we found serologic evidence of a previous exposure to GT1 in 4 patients with non-GT1 infection, and these persons also demonstrated significantly more responses than non-GT1 patients in whom genotype and HCV serotype were identical (P <.001). Comparison of recognition of GT1-specific peptides to peptides representing autologous virus revealed the absence of cross-recognition of the autologous circulating virus. These data indicate that persistent HCV infection can occur in the presence of an HCV-specific T-cell response primed against a heterologous HCV strain, and suggest that clearance of 1 GT does not necessarily protect against subsequent exposure to a second GT.

M3 - SCORING: Zeitschriftenaufsatz

VL - 110

SP - 1559

EP - 1569

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 5

M1 - 5

ER -