TABLE 2.

Virus-cell junctions and complexity in untreated and ETV-treated woodchucks infected with WHV

Woodchuck and treatment groupSample date (wk p.i.)aTotal no. of unique virus-cell junctionsbTotal no. of virus-cell junctionsbComplexity of virus-cell junctionscMinimum cumulative hepatocyte turnoverdCumulative hepatocyte turnover (random)e
Untreated animals
    wc53016981510.650.350.53
    wc535161463120.470.531.1
    wc55819843200.260.742.8
    wc55919572360.240.763.1
    Avg0.41f0.591.88
ETV-treated animals
    wc522161211820.660.340.51
    wc5311639580.670.330.49
    wc533161181380.860.140.16
    Avg0.73f0.270.39
  • a p.i., postinfection.

  • b Extracted liver tissue was analyzed using inverse PCR followed by sequencing for the detection of unique and total virus-cell junctions as described in Materials and Methods.

  • c The complexity of virus-cell junctions was calculated as the ratio of unique to total virus-cell junctions detected.

  • d The minimum cumulative hepatocyte turnover was determined as shown in Fig. 2A as 1.0 minus complexity.

  • e The cumulative hepatocyte turnover due to random killing and compensatory proliferation needed to reach the measured complexity was calculated using the program comp10 described in Materials and Methods. In this simulation infected hepatocytes were assumed to be killed at 20 times the rate of uninfected hepatocytes (1% versus 0.05% per cycle, respectively); virtually identical values were calculated when the death rate for uninfected hepatocytes was set at zero.

  • f The complexity measurements in individual untreated woodchucks were compared to those in the ETV-treated group using a Wilcoxon two-samples, two-sided nonparametric test (P = 0.057), and approached statistical significance.