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 w ith 10(6.0) TCID50 of porcine reproductive and respiratory syndrome virus ( PRRSV) (Lelystad) and euthanized at different time intervals post-inoculati on (p,i,), Bronchoalveolar lavage (BAL) cell populations were characterized , together with the pattern of virus replication and appearance of antibodi es in the lungs. Total BAL cell numbers increased from 140 x 10(6) at 5 day s p,i, to 948 x 10(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 betw een 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 an d 20 days p,i, and that between the same time interval, both 74-22-15-posit ive and 41D3-negative cells, presumably monocytes, and 74-22-15-positive an d 41D3-double negative cells, presumably non-phagocytes, entered the alveol ar spaces. Virus replication was highest at 7 to 9 days p,i,, decreased slo wly thereafter and was detected until 40 days p,i, Anti-PRRSV antibodies we re detected starting at 9 days p,i, but neutralizing antibodies were only d emonstrated in one pig euthanized at 35 days and another at 52 days p.i, Th e decrease of virus replication in the lungs from 9 days p,i, can be attrib uted to (i) shortage of susceptible differentiated macrophages, (ii) lack o f 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.