TABLE 1.
Group and time | No. of animals analyzed | Reporter gene (GFP or RFP) fluorescence in livera | Viremia (mean no. of copies/ml ± SD) | Mean % intrahepatic WHV DNA ± SD
|
Antigen core staining (mean % WHc virus-positive hepatocytes ± SD) | PCNA staining (mean % PCNA-positive hepatocytes ± SD) | Inflammatory activity (mean Metavir score ± SD) | |
---|---|---|---|---|---|---|---|---|
Total DNA (initial total DNA) | cccDNA (initial cccDNA) | |||||||
L-FMAU-FTC | ||||||||
T0 | 6 | − (0/6) | 1.7 × 1010 ± 9.3 × 109 | 100 | 100 | 45 ± 10 | 0.38 ± 0.27 | 1.5 ± 0.58 |
M1 | 6 | 1.1 × 106 ± 1.0 × 106 | 12 ± 4 | 63 ± 19 | 38 ± 5 | 0.67 ± 0.46 | 1.7 ± 0.51 | |
M2 | 5 | − (0/5) | 5.3 × 106 ± 5.0 × 106 | 5 ± 3 | 53 ± 37 | 37 ± 11 | 1.37 ± 0.51 | 1.6 ± 0.54 |
M6 | 5 | 5.6 × 107 ± 9.4 × 107 | 34 ± 13 | 62 ± 58 | 23 ± 18 | 1.32 ± 1.12 | 1.5 ± 0.57 | |
L-FMAU-FTC+Ad-IFN | ||||||||
T0 | 6 | − (0/6) | 2.5 × 1010 ± 7.6 × 109 | 100 | 100 | 52 ± 6 | 0.58 ± 0.25 | 1.2 ± 0.45 |
M1 | 6 | 8.6 × 106 ± 2.5 × 106 | 19 ± 25 | 88 ± 41 | 41 ± 10 | 0.84 ± 0.73 | 2.4 ± 0.89 | |
M2 | 5 | + (5/5) | 4.7 × 106 ± 9.0 × 105 | 11 ± 5 | 76 ± 71 | 45 ± 7 | 1.06 ± 0.61 | 2.5 ± 0.58 |
M6 | 3 | 2.5 × 109 ± 3.7 × 109 | 56 ± 60 | 86 ± 100 | 43 ± 24 | 1.49 ± 0.66 | 2.4 ± 0.50 | |
Ad-IFN | ||||||||
T0 | 2 | − (0/2) | 1.4 × 1010 ± 1.6 × 109 | 100 | 100 | 50 ± 3 | 0.43 ± 0.22 | 2 ± 0 |
M1 | 2 | 2.2 × 1010 ± 9.5 × 109 | 112 ± 18 | 85 ± 16 | 56 ± 5 | 0.98 ± 0.42 | 2 ± 0 | |
M2 | 2 | + (2/2) | 1.4 × 1010 ± 1.5 × 1010 | 113 ± 14 | 80 ± 21 | 55 ± 4 | 1.36 ± 0.04 | 2 ± 0 |
M6 | 1 | 93 | 101 | 59 | 1.06 | 2 ± 0 | ||
Ad-GFP | ||||||||
T0 | 2 | − (0/2) | 1.8 × 1010 ± 1.1 × 1010 | 100 | 100 | 42 ± 3 | 0.95 ± 0.82 | 1.5 ± 0.5 |
M1 | 2 | 1.1 × 1010 ± 9.9 × 109 | 136 ± 85 | 119 ± 51 | 58 ± 9 | 1.2 ± 0.65 | 1.5 ± 0.5 | |
M2 | 2 | + (2/2) | 1.1 × 1010 ± 3.9 × 109 | ND | ND | 49 ± 15 | 1.48 ± 0.74 | 1.5 ± 0.5 |
M6 | 2 | 1.8 × 1010 ± 8.3 × 109 | 166 ± 88 | 126 ± 63 | 49 ± 10 | 0.665 ± 0.83 | 1.5 ± 0.5 | |
Untreated | ||||||||
T0 | 1 | − (0/1) | 1.5 × 1010 | 100 | 100 | 57 | 0.78 | 2 |
M1 | 1 | 1.9 × 1010 | 121 | 85 | 57 | 0.55 | 1.5 | |
M2 | 1 | − (0/1) | 2.8 × 1010 | 127 | 149 | 55 | 0.83 | 2 |
M6 | 1 | 4.0 × 1010 | 160 | 146 | 50 | 0.978 | 2 |
A “+” indicates that specific fluorescence was detected by using confocal microscopy in liver sections. The ratio in parentheses indicates the number of animals that presented a positive fluorescence versus the total liver sections observed per group. All results mentioned here (viremia, intrahepatic DNA, anticore, PCNA staining and Metavir score) are means of the different results obtained for all animals in the same group. For intrahepatic viral DNA, baseline levels were considered arbitrarily as 100%. For WHV core antigen and PCNA staining, the values indicate the mean numbers of hepatocytes expressing these antigens. For liver histology analysis, the mean inflammatory activity score for each animal group is presented.