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Occult infection of peripheral B cells by hepatitis C variants which have low translational efficiency in cultured hepatocytes
  1. Tony Durand1,
  2. Gaëtana Di Liberto1,2,
  3. Hélène Colman1,
  4. Anne Cammas3,
  5. Sebastien Boni1,
  6. Patrick Marcellin2,
  7. Annie Cahour4,
  8. Stephan Vagner3,
  9. Cyrille Féray
  1. 1INSERM U948 and EA 4271, Nantes University, France
  2. 2Centre de Recherche Biomédicale Bichat-Beaujon INSERM 3, France
  3. 3INSERM U563, Toulouse, France
  4. 4UPRES EA 2387, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
  1. Correspondence to Dr Cyrille Féray, INSERM U948, Hôtel-Dieu, 9 quai Moncousu, Nantes 44, France; cyrille.feray{at}univ-nantes.fr

Abstract

Background Plasma hepatitis C virus (HCV) originates from hepatocytes. However, in certain subjects, B cells may harbour both plasma strains and occult HCV strains tha t are not detected in the plasma. The internal ribosome entry site (IRES) of these latter strains is mutated, suggesting that the efficiency of viral translation could drive the cellular tropism of HCV.

Aims To determine if the translational efficiency of IRES variants in cultured hepatocytes or B cells is correlated with their cellular tropism in vivo.

Methods The efficiency of IRES of 10 B cell-specific variants and nine plasma variants, isolated from six patients with compartmentalised variants in B cells, was estimated by bicistronic dual luciferase expression in hepatocyte cell types (Huh7), in primary cultured human hepatocytes (PCHs) and in two B cell lines (Raji and Daudi).

Results For each of the six subjects, the plasma IRESes were significantly and repeatedly more efficient than B cell IRESes in Huh7 (1.7±0.3 vs 0.7±0.2; p<0.01) and PCH cells. In B cell lines, B cell and plasma IRES had similar low efficiencies (0.8±0.1 vs 0.9±0.1; NS). For three subjects, two IRES variants from the same compartment could be analysed, and had the same efficiency in each cell type. Silencing the lupus antigen, a known IRES trans-acting factor, inhibited plasma IRES variants to a greater extent than B cell-specific IRESes.

Conclusions B cells can harbour occult variants that have a poor translational efficiency in hepatocytes, strongly suggesting their extra-hepatic origin and raising the hypothesis that competition between HCV variants with different IRESes is driven at a translational level in hepatic, as well as in extra-hepatic, sites.

  • HCV
  • hepatitis

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Footnotes

  • Linked articles 210054.

  • Funding This work was supported by the French National agency for AIDS and hepatitis research (ANRS).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the CHU Nantes.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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