RESUMEN
PRRSV can replicate for months in lymphoid organs leading to persistent host infections. Porcine bone marrow comprises two major monocyte subsets, one of which expresses CD163 and CD169, two receptors involved in the entry of PRRSV in macrophages. In this study, we investigate the permissiveness of these subsets to PRRSV infection. PRRSV replicates efficiently in BM CD163+ monocytes reaching titers similar to those obtained in alveolar macrophages, but with a delayed kinetics. Infection of BM CD163- monocytes was variable and yielded lower titers. This may be related with the capacity of BM CD163- monocytes to differentiate into CD163+ CD169+ cells after culture in presence of M-CSF. Both subsets secreted IL-8 in response to virus but CD163+ cells tended to produce higher amounts. The infection of BM monocytes by PRRSV may contribute to persistence of the virus in this compartment and to hematological disorders found in infected animals such as the reduction in the number of peripheral blood monocytes.
Asunto(s)
Células de la Médula Ósea/virología , Médula Ósea/inmunología , Monocitos/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Animales , Antígenos CD/efectos de los fármacos , Antígenos CD/inmunología , Antígenos de Diferenciación Mielomonocítica/efectos de los fármacos , Antígenos de Diferenciación Mielomonocítica/inmunología , Médula Ósea/virología , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/inmunología , Células Cultivadas , Interacciones Huésped-Patógeno/inmunología , Interleucina-8/inmunología , Interleucina-8/metabolismo , Factor Estimulante de Colonias de Macrófagos/genética , Factor Estimulante de Colonias de Macrófagos/farmacología , Monocitos/clasificación , Monocitos/inmunología , Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/inmunología , Receptores de Superficie Celular/efectos de los fármacos , Receptores de Superficie Celular/inmunología , Lectina 1 Similar a Ig de Unión al Ácido Siálico/efectos de los fármacos , Lectina 1 Similar a Ig de Unión al Ácido Siálico/inmunología , Porcinos , Replicación ViralRESUMEN
CD169 and CD163 have been involved in the process of PRRS virus attachment and infection in macrophages, although recent studies have challenged the requirement for CD169. In addition to CD169, macrophages express other siglecs, whose role in PRRS virus infection is so far unknown. Splenic CD163+ macrophages express Siglec-3 and Siglec-5 but almost undetectable levels of CD169. Hence, we considered this cell population appropriate for analysing the role of these siglecs in the attachment and internalization of PRRS virus into macrophages. PRRS virus replicated efficiently in these macrophages, yielding even higher titres than in alveolar macrophages. Besides, a recombinant protein consisting in the ectodomain of porcine Siglec-3 fused to the Fc fragment of human IgG1 (Siglec3-Fc) was able to bind PRRS virus, while binding to Siglec-5-Fc was inconsistent. Antibodies to CD169 but not to Siglec-3 or Siglec-5 blocked the binding and infection of PRRS virus on alveolar macrophages. Unexpectedly, our antibody to CD169 also blocked the binding of PRRS virus to splenic CD163+ macrophages, whereas antibodies to Siglec-3 or Siglec-5 had no effect. These results show that very low levels of CD169 expression are enough to support the attachment and internalization of PRRS virus into macrophages, whereas Siglec-3 and Siglec-5 do not seem to contribute to the virus entry in these cells.