Previously infected chimpanzees are not consistently protected against reinfection or persistent infection after reexposure to the identical hepatitis C virus strain

被引:70
作者
Bukh, Jens [1 ,2 ,3 ,4 ]
Thimme, Robert [5 ]
Meunier, Jean-Christophe [1 ]
Faulk, Kristina [1 ]
Spangenberg, Hans Christian [5 ]
Chang, Kyong-Mi [5 ]
Satterfield, William [6 ]
Chisari, Francis V. [5 ]
Purcell, Robert H. [1 ]
机构
[1] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA
[2] Univ Copenhagen Hosp, Dept Infect Dis, Copenhagen Hepatitis Program C, DK-2650 Hvidovre, Denmark
[3] Univ Copenhagen Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark
[4] Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, DK-2200 Copenhagen N, Denmark
[5] Scripps Res Inst, Dept Mol & Expt Med, Div Expt Pathol, La Jolla, CA 92037 USA
[6] MD Anderson Canc Ctr, Michale E Keeling Ctr Comparat Med & Res, Dept Vet Sci, Bastrop, TX 78602 USA
关键词
D O I
10.1128/JVI.00142-08
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Protective immunity after resolved hepatitis C virus (HCV) infection has been reported. However, the breadth of this immunity has remained controversial, and the role of neutralizing antibodies has not been well-defined. In the present study, two chimpanzees (CH96A008 and CH1494) with resolved monoclonal H77C (genotype 1a) infection were rechallenged with low-dose homologous H77C virus about 12 months after viral clearance; CH96A008 became persistently infected, and CH1494 had transient viremia lasting 2 weeks. CH1494 was subsequently either partially or completely protected following five homologous rechallenges with monoclonal H77C or polyclonal H77 and after six heterologous rechallenges with HC-J4 (genotype 1b) or HC-J6 (genotype 2a) viruses. Subsequently, a final challenge with H77C resulted in persistent HCV infection. In both chimpanzees, serum neutralizing antibodies against retroviral pseudoparticles bearing the H77C envelope proteins were not detected during the initial infection or during rechallenge. However, anamnestic cellular immune responses developed during the initial homologous rechallenge, in particular in CH96A008, which developed a persistent infection. Polyprotein sequences of viruses recovered from CH1494 after the two homologous rechallenges that resulted in transient viremia were identical with the H77C virus. In contrast, the polyprotein sequences of viruses recovered from both chimpanzees after homologous rechallenge resulting in persistent infection had numerous changes. These findings have important implications for our understanding of immunity against HCV; even in the best-case scenario with autologous rechallenge, low-level viral persistence was seen in the presence of primed T-cell responses.
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收藏
页码:8183 / 8195
页数:13
相关论文
共 36 条
[1]   In vitro assay for neutralizing antibody to hepatitis C virus:: Evidence for broadly conserved neutralization epitopes [J].
Bartosch, B ;
Bukh, J ;
Meunier, JC ;
Granier, C ;
Engle, RE ;
Blackwelder, WC ;
Emerson, SU ;
Cosset, FL ;
Purcell, RH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (24) :14199-14204
[2]   Protective immune response to hepatitis C virus in chimpanzees rechallenged following clearance of primary infection [J].
Bassett, SE ;
Guerra, B ;
Brasky, K ;
Miskovsky, E ;
Houghton, M ;
Klimpel, GR ;
Lanford, RE .
HEPATOLOGY, 2001, 33 (06) :1479-1487
[3]   Adaptive immune responses in acute and chronic hepatitis C virus infection [J].
Bowen, DG ;
Walker, CM .
NATURE, 2005, 436 (7053) :946-952
[4]   Mutational escape from CD8+ T cell immunity:: HCV evolution, from chimpanzees to man [J].
Bowen, DG ;
Walker, CM .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (11) :1709-1714
[5]   Experimental infection of chimpanzees with hepatitis C virus of genotype 5a: Genetic analysis of the virus and generation of a standardized challenge pool [J].
Bukh, J ;
Apgar, CL ;
Engle, R ;
Govindarajan, S ;
Hegerich, PA ;
Tellier, R ;
Wong, DC ;
Elkins, R ;
Kew, MC .
JOURNAL OF INFECTIOUS DISEASES, 1998, 178 (04) :1193-1197
[6]   A critical role for the chimpanzee model in the study of hepatitis C [J].
Bukh, J .
HEPATOLOGY, 2004, 39 (06) :1469-1475
[7]   Studies of hepatitis C virus in chimpanzees and their importance for vaccine development [J].
Bukh, J ;
Forns, X ;
Emerson, SU ;
Purcell, RH .
INTERVIROLOGY, 2001, 44 (2-3) :132-142
[8]  
Bukh J, 2002, VIRAL HEPATITIS LIVE, P336
[9]   Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein [J].
Farci, P ;
Shimoda, A ;
Wong, D ;
Cabezon, T ;
DeGioannis, D ;
Strazzera, A ;
Shimizu, Y ;
Shapiro, M ;
Alter, HJ ;
Purcell, RH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (26) :15394-15399
[10]   PREVENTION OF HEPATITIS-C VIRUS-INFECTION IN CHIMPANZEES AFTER ANTIBODY-MEDIATED IN-VITRO NEUTRALIZATION [J].
FARCI, P ;
ALTER, HJ ;
WONG, DC ;
MILLER, RH ;
GOVINDARAJAN, S ;
ENGLE, R ;
SHAPIRO, M ;
PURCELL, RH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (16) :7792-7796