KINETICS OF DUCK HEPATITIS-B VIRUS-INFECTION FOLLOWING LOW-DOSE VIRUSINOCULATION - ONE VIRUS-DNA GENOME IS INFECTIOUS IN NEONATAL DUCKS

Using pooled serum from congenitally duck hepatitis 9 virus (DHBV)-inf ected ducks as inoculum, we examined the effect of virus dose on the i ncubation period of infection and on the patterns of spread of virus i nfection in the liver. The pealed serum inoculum contained 9.5 x 10(9) DHBV genomes per milliliter and had an infectivity titre (ID50) in ne wly hatched ducks of 1.5 x 10(10) per milliliter with a 95% confidence interval of 3.0 x 10(8) to 6.3 x 10(10) ID50/ml, indicating the equiv alence between one DHBV genome and one infectious unit within the limi ts of the assays. The incubation period of infection was inversely rel ated to the dose of inoculum and the onset of viraemia ranged from Day 6 with the highest dose to Day 14 or 29 with the lowest dose inoculum . To study the spread of virus infection from a low percentage of init ially infected cells we inoculated newly hatched ducks intravenously w ith sufficient DHBV (1.5 x 10(3) ID50) to infect only similar to 0.000 1% of total liver cells. DHBV infection first reached detectable level s on Day 4 postinoculation (p.l.) and was detected in similar to 0.035 % of hepatocytes, most of which occurred as single cells or pairs of c ells, indicating that a number of rounds of infection had occurred wit h the spread of virus both to adjoining cells, i.e., by cell-to-cell s pread, and to cells located In other parts of the liver lobule. Despit e some bird-to-bird variation in timing, the percentage of infected he patocytes increased exponentially with a mean doubling time of 16 hr f rom Day 4 to Day 14 p.i., by which time replication was seen in >95% o f hepatocytes. This rapid dissemination from a smalt number of infecte d hepatocytes suggests that in neonatal ducks, there are no major dela ys in virus replication within the liver, that any innate and adaptive defence mechanisms operating during the first 10 to 14 days of infect ion are insufficient to contain virus spread, and that even a small nu mber of infected hepatocytes produce enough progeny to rapidly infect the remaining hepatocytes. (C) 1996 Academic Press. Inc