HBeAg defective mutants in active/inactive anti-HBe positive HBV carriers: possible role of pre-core initiation mutants.

FLICHMAN D, CAVALLONE D, BIAGIONI R, OLIVERI F, CICCOROSSI P, COCO B, COLOMBATTO P, SACCO R, BONINO F, BRUNETTO M

Paris

Congreso; 9th Annual Meeting European Society for Clinical Virology; 2006

&amp;amp;amp;amp;amp;lt;!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-GB;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --&amp;amp;amp;amp;amp;gt; Background and Objectives: Mutations that modulate HBeAg expression at translational or transcriptional levels are present in anti-HBe-positive HBsAg carriers, but their relationship with active and inactive infections is unclear. Methods: We characterize by direct sequencing Basic Core promoter (BCP) HBV mutants in 104 chronic anti-HBe positive carriers, followed prospectively for 25.3 months (range: 12-32) and classified as inactive (26) or active (78) according to 12-month persistence of normal ALT and HBV-DNA levels <5 log10 cp/ml. Results: BCP and pC mutants were found in all cases [1762T: 60.8%; 1764A; 68.6%; 1896:72.5%; 1899A: 52%; 2bp insertion 1.0%; 1817T: 2.9% and pre-Core initiation codon (PIC): 10.8%]. The 1896A single mutation pattern prevailed in younger than older (>50 years) carriers (29.6% vs 0.0% p<0.001). Mutations at nt 1762, 1764 and 1896 had lower prevalence in inactive than active carriers [37.5% vs. 67.9% (p=0.009)], 45.8% 75.6% (p=0.011), 58.6% vs 78.9% (n.s.)] respectively; whereas 1899 mutation was evenly distributed in the 2 groups (50% vs 53%). PIC variants prevailed in inactive HBV genotype D carriers (29.2% vs 5.3% p<0.003) and were associated with ALT flares in active carriers. Conclusions: BCPpC mutations are the hallmark of chronic anti-HBe positive HBV infection. Translational pC mutants prevail in younger whereas transcriptional BCP mutants might provide selective viral fitness in older and active HBV carriers. PIC mutations in inactive HBV genotype D carriers might play a role in shifting from active to inactive infection. In vitro studies are in progression to verify the replication efficiency of isolates with and without PIC mutations.