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Abstract Details
Hepatic immunopathology during occult hepacivirus re-infection
Manickam C1, Martinot AJ1, Jones RA1, Varner V1, Reeves RK2. Virology. 2017 Sep 12;512:48-55. doi: 10.1016/j.virol.2017.08.037. [Epub ahead of print]
Author information
1
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
2
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA. Electronic address: rreeves@bidmc.harvard.edu.
Abstract
Despite drug advances for Hepatitis C virus (HCV), re-infections remain prevalent in high-risk populations. Unfortunately, the role of preexisting viral immunity and how it modulates re-infection is unclear. GBV-B infection of common marmosets is a useful model to study tissue immune responses in hepacivirus infections, and in this study we re-challenged 4 animals after clearance of primary viremia. Although only low-to-absent viremia was observed following re-challenge, GBV-B viral RNA was detectable in liver, confirming re-infection. Microscopic hepatic lesions indicated severe-to-mild lymphocyte infiltration and fibrosis in 3 out of 4 animals. Further, GBV-B-specific T cells were elevated in animals with moderate-to-severe hepatopathology, and up to 3-fold increases in myeloid dendritic and activated natural killer cells were observed after infection. Our data indicate that occult hepacivirus re-infections occur and that new liver pathology is possible even in the presence of anti-hepacivirusT cells and in the absence of high viremia.