Divergent evolution of hepatitis C virus in liver and peripheral blood mononuclear cells of infected patients

Maggi, Fabrizio; Fornai, Claudia; Morrica, Antonietta; Vatteroni, Maria Linda; Giorgi, Massimo; Marchi, Santino; Ciccorossi, P.; Bendinelli, Mauro; Pistello, Mauro

doi:10.1002/(sici)1096-9071(199901)57:1<57::aid-jmv8>3.3.co;2-i

Cited by 5 publications

(9 citation statements)

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“…This study of immunocompetent subjects with chronic hepatitis C demonstrates that HCV quasispecies compartmentalization among plasma and BMC subsets, based on analysis of the HVR1 region, is a common phenomenon. Previous studies had already pointed to HCV HVR1 compartmentalization, but appropriate statistical methods were not used and the nature of the cellular subsets was not investigated 10, 23. By using the Mantel's test, which does not depend only on the interpretation of phylogenetic trees, we found that B cells and monocytes were the main BMC subsets involved in HCV compartmentalization, and that variants harbored by B cells and monocytes were always different from each other.…”

Section: Discussionmentioning

confidence: 83%

“…Subsequently, it was found that blood mononuclear cells (BMC) from chimpanzees that had been inoculated with this strain became infected by the same lymphotropic quasispecies components as those selected in vitro 6. In vivo , HCV RNA has been detected in BMC by many teams 7–14. Viral replication in these cells, shown by the detection of negatively stranded HCV RNA, an obligatory replication intermediate, generally occurs at a low level 9, 15–18.…”

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confidence: 99%

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Frequent compartmentalization of hepatitis C virus variants in circulating B cells and monocytes

Ducoulombier¹,

Roque–Afonso²,

Liberto³

et al. 2004

Hepatology

135

109

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Differences in the composition of the hepatitis C virus (HCV) quasispecies between plasma and blood mononuclear cells (BMC) strongly suggest that BMCs support viral replication. We examined the frequency of such compartmentalization, the cell types involved, the constraints exerted on the different variants, and the role of immunoglobulin-complexed variants. We screened the hypervariable region (HVR1) of HCV isolates from 14 HBsAg-and HIV-seronegative patients with chronic HCV infection. HCV RNA was amplified and cloned from plasma, the immunoglobulin G (IgG)-bound fraction, and total and sorted BMCs (CD19؉, CD8؉, CD4؉, and CD14؉ cells). Compartmentalization was estimated using a matrix correlation test. The ratio of nonsynonymous/synonymous substitutions (d N /d S ratio) was calculated for each compartment. HCV RNA was detected in 3/3 BMC, 11/11 CD19؉, 10/11 CD14؉, 4/11 CD8؉ and 0/11 CD4؉ cell samples. HVR1 sequences were significantly different between plasma and at least one cellular compartment in all nine cases analyzed, and between B cells (CD19؉) and monocytes ( H epatitis C virus (HCV) is an enveloped, positive-stranded RNA virus that circulates in vivo as a complex population of closely related variants referred to as a quasispecies. 1 Hepatitis C infection is frequently chronic, and its quasispecies nature probably plays a major role in viral persistence. 2,3 HCV genetic heterogeneity is particularly strong within a small hypervariable region (HVR1) that encodes a 27-amino acid peptide located at the N-terminus of the second envelope glycoprotein (E2) and is subjected to selective pressures by humoral and cellular immune responses. 4 One potential viral strategy explaining the persistence of HCV is infection of immune cells. Convincing evidence of HCV lymphotropism has been obtained in vitro in experiments showing that minor quasispecies components of strain H77 are selected in lymphoblastoid cell lines. 5 Subsequently, it was found that blood mononuclear cells (BMC) from chimpanzees that had been inoculated with this strain became infected by the same lymphotropic quasispecies components as those selected in vitro. 6 In vivo, HCV RNA has been detected in BMC by many teams. 7-14 Viral replication in these cells, shown by the detection of negatively stranded HCV RNA, an obligatory replication intermediate, generally occurs at a low level. 9,[15][16][17][18] Mutations in the 5Ј untranslated region-the viral internal ribosomal entry site-have been described in HCV strains isolated from BMCs. These mutations could influence the translational efficiency of the internal ribosomal entry site structure in lymphoblastoid cell lines 19 and point to HCV adaptation to BMCs. 6,20,21

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Section: Discussionmentioning

confidence: 83%

mentioning

confidence: 99%

Frequent compartmentalization of hepatitis C virus variants in circulating B cells and monocytes

Ducoulombier¹,

Roque–Afonso²,

Liberto³

et al. 2004

Hepatology

135

109

View full text Add to dashboard Cite

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“…The existence of HCV quasispecies with affinity to immune cells has been suggested shortly after HCV discovery [37][38][39]. Evidence for lymphotropic HCV variants was found in patients with CHC, acute hepatitis C, as well as in asymptomatic individuals with persistent OCI [4,14,15,[40][41][42][43][44][45][46][47]. Analyses of HCV variants residing in PBMC by clonal sequencing and single-stranded conformational polymorphism (SSCP) revealed features which argued against the possibility of carry-over of variants from plasma-derived HCV RNA or from virus nonspecifically attached to the cell surface [5-9, 13, 15, 42, 48, 49].…”

Section: Hcv Compartmentalization In the Immune Systemmentioning

confidence: 99%

HCV Lymphotropism and Its Pathogenic Significance

Michalak¹

2018

Hepatitis C - From Infection to Cure

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Hepatitis C virus (HCV) is not only a hepatotropic but also a lymphotropic virus. Infection of the immune system appears to be a natural propensity of HCV and, as the accumulated data indicate, a common characteristic of both symptomatic and clinically silent but molecularly evident infection known as occult infection. The ability of HCV to infect cells of the immune system is consistent with a significantly greater prevalence of certain lymphoproliferative disorders in HCV-infected patients, such as mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma. This chapter recapitulates the approaches used to detect HCV and its replication within lymphoid cells, features of HCV compartmentalization in the lymphatic system and in different types of immune cells, and the cell culture models developed to study HCV lymphotropism. In addition, the characteristics of the molecules recently identified as those specifically mediating HCV entry leading to virus replication in B and T lymphocytes, which are distinct from those involved in virus entry to hepatocytes, are presented. Finally, the biological impact of HCV lymphotropism on the function of immune cells, virus persistence, and immune cell proliferation and lymphomagenesis is summarized.

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“…HCV has been isolated from monocytes/macrophages, B lymphocytes, thyroid tissue, renal biopsy tissue, and pancreas biopsy tissue (16–19). Interestingly, the diversity of genotypes noted in isolates from different tissues would suggest that altered cellular trophism and viral partitioning into extrahepatic reservoirs does exist among the different genotypes of HCV and may, in part, explain the diversity of extraheptatic manifestations seen (20–25). Although there is no reported experience in using HCV + donors for pancreas transplantation of either HCV + or HCV − recipients, these new data raise theoretical concerns regarding exposure of recipients to various HCV genotypes with diverse patterns of extrahepatic trophism.…”

Section: Discussionmentioning

confidence: 99%

Impact of hepatitis C virus status in pancreas transplantation: a case controlled study

Honaker

Stratta

et al. 2002

Clinical Transplantation

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Available data suggest that hepatitis C virus positive (HCV+) renal transplant patients may be at an increased risk of morbidity and mortality compared with HCV- patients. Limited data are available regarding the impact of HCV status in pancreas transplant patients. We compared the outcomes of 10 HCV+ patients undergoing pancreas transplantation (seven simultaneous kidney-pancreas, one pancreas after kidney, two pancreas alone) between 1/96 and 10/99 with 20 HCV- recipients that were matched for age, race, gender, timing of transplant, type of pancreas transplant, and surgical technique. Length of follow-up was not significantly different between the HCV+ group compared with the HCV- group (24 +/- 14 vs. 20 +/- 13 months; p=0.45). There was a trend toward a higher incidence of all cause mortality in HCV+ recipients compared with HCV- recipients, 30 vs. 10%, respectively (p=0.17). Additionally, the HCV+ recipients had a trend toward a higher incidence of sepsis-related mortality compared with HCV- recipients, 20 vs. 5%, respectively (p=0.19). Renal allograft survival was 50% in the HCV+ group compared with 94% in the HCV- group (p=0.02). Pancreas allograft survival was not significantly different between the groups, 60 vs. 80%, respectively (p=0.24). At 3, 6, 12 months, and end of follow-up, there were no differences in serum creatinine, amylase, C-peptide, or fasting glucose levels. However, there was a significantly higher incidence of proteinuria at last follow-up in the HCV+ recipients with a renal allograft when compared with HCV- recipients, 50 vs. 12.5%, respectively (p=0.05). In order to maintain comparable glycemic control between the groups, there was a significant increase in oral hypoglycemic requirement in HCV+ recipients compared with HCV- recipients, 33 vs. 0%, respectively (p=0.01). These data suggest that HCV+ pancreas transplant patients may be at an increased risk of graft dysfunction and morbidity. Further studies with more patients and longer follow-up are needed to fully define the impact of HCV status on pancreas graft survival and function.

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Divergent evolution of hepatitis C virus in liver and peripheral blood mononuclear cells of infected patients

Cited by 5 publications

References 0 publications

Frequent compartmentalization of hepatitis C virus variants in circulating B cells and monocytes

Frequent compartmentalization of hepatitis C virus variants in circulating B cells and monocytes

HCV Lymphotropism and Its Pathogenic Significance

Impact of hepatitis C virus status in pancreas transplantation: a case controlled study

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