Frequent Compartmentalization of Hepatitis C Virus with Leukocyte-Related Amino Acids in the Setting of Liver Transplantation

• Published in: The Journal of infectious diseases 2008-12, Vol.198 (11), p.1656-1666
• Main Authors: Schramm, Frédéric, Soulier, Eric, Royer, Cathy, Weitten, Thierry, Fafi-Kremer, Samira, Brignon, Nicolas, Meyer, Nicolas, Ellero, Bernard, Woehl-Jaegle, Marie-Lorraine, Meyer, Carole, Wolf, Philippe, Doffoël, Michel, Baumert, Thomas F., Stoll-Keller, Françoise, Schvoerer, Evelyne
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Amino Acids - blood; B lymphocytes; Biological and medical sciences; Blood plasma; Evolution; Evolution, Molecular; Evolutionary genetics; Fundamental and applied biological sciences. Psychology; Genetic Variation; Hepacivirus; Hepacivirus - genetics; Hepacivirus - physiology; Hepatitis C virus; Human health and pathology; Humans; Infectious diseases; Leukocytes, Mononuclear - virology; Life Sciences; Liver; Liver transplantation; Liver Transplantation - adverse effects; Medical sciences; Microbiology; Microbiology and Parasitology; Miscellaneous; Molecular Sequence Data; Phylogenetics; Phylogeny; Selection, Genetic; Viral Proteins - chemistry; Viral Proteins - genetics; Virology; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/592986

Background. Nonrandom distribution of hepatitis C virus (HCV) quasispecies (compartmentalization between blood plasma and leukocytes) suggests the presence of HCV leukotropic variants. HCV compartmentalization in the setting of liver transplantation (LT) is poorly understood. To study HCV leukotropic variants, we investigated the evolution of HCV compartmentalization after immunosuppression in liver transplant recipients. Methods. Plasma and peripheral blood mononuclear cell (PBMC) samples were collected from 5 liver transplant recipients before and after LT. We used clone sequencing to analyze the hypervariable region 1 (HVR1)-E2384–419 region, which plays a key role in HCV entry and the induction of neutralizing responses, and assessed compartmentalization through phylogenetic analyses and Mantel's test. Results. Compartmentalization was frequent in the LT setting. HCV quasispecies were more homogeneous after LT in both the plasma and PBMC compartments, with a significant decrease in quasispecies complexity (P = .003) and genetic distances (P = .004) after transplantation. Our analysis identified 8 PBMC-related amino acid residues in HVR1. Conclusions. HCV compartmentalization between plasma and PBMCs and the emergence of leukotropic variants could be potentiated by immunosuppression in liver transplant recipients. The identification of defined leukotropic variants may contribute to the understanding of virus-host interactions after transplantation.