Effect of cellular changes and onset of humoral immunity on the replication of porcine reproductive and respiratory syndrome virus in the lungs of pigs.

Twenty-two 4- to 5-week-old gnotobiotic pigs were intranasally inoculated with 10(6.0) TCID(50) of porcine reproductive and respiratory syndrome virus (PRRSV) (Lelystad) and euthanized at different time intervals post-inoculation (p.i.). Bronchoalveolar lavage (BAL) cell populations were characterized, together with the pattern of virus replication and appearance of antibodies in the lungs. Total BAL cell numbers increased from 140x10(6) at 5 days p.i. to 948x10(6) at 25 days p.i. and remained at high levels until the end of the experiment. The number of monocytes/macrophages, as identified by monoclonal antibodies 74-22-15 and 41D3, increased two- to fivefold between 9 and 52 days p.i. with a maximum at 25 days p.i. Flow cytometry showed that the population of differentiated macrophages was reduced between 9 and 20 days p.i. and that between the same time interval, both 74-22-15-positive and 41D3-negative cells, presumably monocytes, and 74-22-15- and 41D3-double negative cells, presumably non-phagocytes, entered the alveolar spaces. Virus replication was highest at 7 to 9 days p.i., decreased slowly thereafter and was detected until 40 days p.i. Anti-PRRSV antibodies were detected starting at 9 days p.i. but neutralizing antibodies were only demonstrated in one pig euthanized at 35 days and another at 52 days p.i. The decrease of virus replication in the lungs from 9 days p.i. can be attributed to (i) shortage of susceptible differentiated macrophages, (ii) lack of susceptibility of the newly infiltrated monocytes and (iii) appearance of anti-PRRSV antibodies in the lungs. Neutralizing antibodies may contribute to the clearance of PRRSV from the lungs.