Identification of a novel HBV precorecore deletion mutant in HIVHBV coinfected individuals.

1
Identification of a novel HBV precore/core
deletion mutant in HIV/HBV co-infected
individuals.
Peter Revill, Margaret Littlejohn, Anna Ayres,
Angeline Bartholomeusz, Lilly Yuen, Liza Cabuang,
Danni Colledge, Joe Sasadeusz, Sharon Lewin,
Gregory Dore, Gail Matthews, Chloe Thio and
Stephen Locarnini Victorian Infectious Diseases
Reference Laboratory
This project is funded by NIH grant AIO60449
VIDRL
2

• Co-infection with HBV is common in HIV infected
  persons Alter, J Hepatol, 2006 Cooley et al., J.
  Clin Virol, 2003.
• Co-infection associated with increased HBV
  replication and 14 fold increased risk of
  liver-related mortality Thio et al.,Lancet,2002.
• We have identified a novel 1G HBV deletion
  mutant significantly associated with HIV/HBV
  co-infection (plt0.001)
• Frameshift resulted in truncation of the deduced
• nucleocapsid and HBeAg proteins.
• The mutant was the dominant virus in some
  individuals (9/10 clones), but wild-type HBV was
  always detected.

• Analysis of 58 samples showed the 1G mutant was
  associated with high HBV viral DNA levels
  (p0.002)

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In vitro analysis

• Although incapable of autonomous replication,
  replication of the 1G mutant was restored by HBV
  core protein supplied in trans (lane 3)
• The rescued 1G mutant was HBeAg negative.

M 1 2 3 4
HBeAg
1500 bp

1. WT/EV 11 2. WT/pCIcore 11 3. -1G/pCI core
11 4.-1G/EV.
1. WT/EV 2. WT/core 3. 1G/EV 4. 1G/Core 5.
pCI precore 6. pCI core