HDV Can Constrain HBV Genetic Evolution in HBsAg: Implications for the Identification of Innovative Pharmacological Targets
AbstractChronic HBV + HDV infection is associated with greater risk of liver fibrosis, earlier hepatic decompensation, and liver cirrhosis hepatocellular carcinoma compared to HBV mono-infection. However, to-date no direct anti-HDV drugs are available in clinical practice. Here, we identified conserved and variable regions in HBsAg and HDAg domains in HBV + HDV infection, a critical finding for the design of innovative therapeutic agents. The extent of amino-acid variability was measured by Shannon-Entropy (Sn) in HBsAg genotype-d sequences from 31 HBV + HDV infected and 62 HBV mono-infected patients (comparable for demographics and virological-parameters), and in 47 HDAg genotype-1 sequences. Positions with Sn = 0 were defined as conserved. The percentage of conserved HBsAg-positions was significantly higher in HBV + HDV infection than HBV mono-infection (p = 0.001). Results were confirmed after stratification for HBeAg-status and patients’ age. A Sn = 0 at specific positions in the C-terminus HBsAg were correlated with higher HDV-RNA, suggesting that conservation of these positions can preserve HDV-fitness. Conversely, HDAg was characterized by a lower percentage of conserved-residues than HBsAg (p < 0.001), indicating higher functional plasticity. Furthermore, specific HDAg-mutations were significantly correlated with higher HDV-RNA, suggesting a role in conferring HDV replicative-advantage. Among HDAg-domains, only the virus-assembly signal exhibited a high genetic conservation (75% of conserved-residues). In conclusion, HDV can constrain HBsAg genetic evolution to preserve its fitness. The identification of conserved regions in HDAg poses the basis for designing innovative targets against HDV-infection. View Full-Text
- Supplementary File 1:
PDF-Document (PDF, 969 KB)
Share & Cite This Article
Colagrossi, L.; Salpini, R.; Scutari, R.; Carioti, L.; Battisti, A.; Piermatteo, L.; Bertoli, A.; Fabeni, L.; Minichini, C.; Trimoulet, P.; Fleury, H.; Nebuloso, E.; De Cristofaro, M.; Cappiello, G.; Spanò, A.; Malagnino, V.; Mari, T.; Barlattani, A.; Iapadre, N.; Lichtner, M.; Mastroianni, C.; Lenci, I.; Pasquazzi, C.; De Sanctis, G.M.; Galeota Lanza, A.; Stanzione, M.; Stornaiuolo, G.; Marignani, M.; Sarmati, L.; Andreoni, M.; Angelico, M.; Ceccherini-Silberstein, F.; Perno, C.-F.; Coppola, N.; Svicher, V. HDV Can Constrain HBV Genetic Evolution in HBsAg: Implications for the Identification of Innovative Pharmacological Targets. Viruses 2018, 10, 363.
Colagrossi L, Salpini R, Scutari R, Carioti L, Battisti A, Piermatteo L, Bertoli A, Fabeni L, Minichini C, Trimoulet P, Fleury H, Nebuloso E, De Cristofaro M, Cappiello G, Spanò A, Malagnino V, Mari T, Barlattani A, Iapadre N, Lichtner M, Mastroianni C, Lenci I, Pasquazzi C, De Sanctis GM, Galeota Lanza A, Stanzione M, Stornaiuolo G, Marignani M, Sarmati L, Andreoni M, Angelico M, Ceccherini-Silberstein F, Perno C-F, Coppola N, Svicher V. HDV Can Constrain HBV Genetic Evolution in HBsAg: Implications for the Identification of Innovative Pharmacological Targets. Viruses. 2018; 10(7):363.Chicago/Turabian Style
Colagrossi, Luna; Salpini, Romina; Scutari, Rossana; Carioti, Luca; Battisti, Arianna; Piermatteo, Lorenzo; Bertoli, Ada; Fabeni, Lavinia; Minichini, Carmine; Trimoulet, Pascale; Fleury, Hervé; Nebuloso, Elena; De Cristofaro, Maria; Cappiello, Giuseppina; Spanò, Alberto; Malagnino, Vincenzo; Mari, Terenzio; Barlattani, Angelo; Iapadre, Nerio; Lichtner, Miriam; Mastroianni, Claudio; Lenci, Ilaria; Pasquazzi, Caterina; De Sanctis, Giuseppe M.; Galeota Lanza, Alfonso; Stanzione, Maria; Stornaiuolo, Gianfranca; Marignani, Massimo; Sarmati, Loredana; Andreoni, Massimo; Angelico, Mario; Ceccherini-Silberstein, Francesca; Perno, Carlo-Federico; Coppola, Nicola; Svicher, Valentina. 2018. "HDV Can Constrain HBV Genetic Evolution in HBsAg: Implications for the Identification of Innovative Pharmacological Targets." Viruses 10, no. 7: 363.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.