CD163 Expression Confers Susceptibility to Porcine Reproductive and Respiratory Syndrome Viruses

Calvert, Jay G.; Slade, David E.; Shields, Shelly; Jolie, Rika; Mannan, Ramasamy M.; Ankenbauer, Robert G.; Welch, Siao-Kun W.

doi:10.1128/jvi.00513-07

Cited by 295 publications

(251 citation statements)

References 34 publications

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“…Most likely, endosomal acidification activates proteases such as cathepsin E or other serine proteases, which are involved in the uncoating of PRRSV. In addition, transient transfection of CD163 was shown to enable PRRSV replication in non-susceptible cells and CD163 antibodies were shown to interfere with infection of Marc-145 cells [6]. These results suggests that besides a critical role of CD163 in PRRSV entry in Marc-145 cells, this molecule might also be involved in PRRSV entry in macrophages, however this needs to be addressed in more detail in studies with primary macrophages.…”

Section: Discussionmentioning

confidence: 94%

“…Attachment of PRRSV to sialoadhesin is mediated by sialic acids present on the surface of PRRS virions [14,16]. CD163, a cellular protein in the scavenger receptor cysteine-rich superfamily, has recently been shown also to function as a PRRSV receptor in Marc-145 cells, but its role in PRRSV infection of primary macrophages has not been studied [6].…”

Section: Introductionmentioning

confidence: 99%

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Involvement of proteases in porcine reproductive and respiratory syndrome virus uncoating upon internalization in primary macrophages

2008

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-Porcine reproductive and respiratory syndrome virus (PRRSV) replicates in differentiated macrophages. In macrophages, heparan sulphate glycosaminoglycans mediate the initial PRRSV attachment and the receptor sialoadhesin mediates both PRRSV attachment and internalization into endosomes. Upon a pH drop, PRRSV is uncoated and its genome is released from the endosomes into the cytoplasm, which allows virus replication. However, expression of heparan sulphate and sialoadhesin in non-susceptible cells only allows virus internalization, but no virus uncoating and infection, indicating that other factors are involved. In the present study, it is shown that treatment of macrophages with serum (mainly the alpha-globulin fraction) inhibited PRRSV infection without affecting attachment and internalization. Because alpha-globulins contain several protease inhibitors, macrophages were treated with different protease inhibitors to investigate the involvement of proteases in PRRSV uncoating. Treatment of macrophages with broadly active inhibitors of serine or aspartic proteases, but not cysteine-or metallo-proteases, inhibited PRRSV uncoating and infection. Further investigation using specific inhibitors indicated that the aspartic protease cathepsin E is involved during PRRSV uncoating, but did not allow identification of the serine protease involved. The involvement of cathepsin E during PRRSV uncoating was confirmed by partial co-localization of internalized PRRSV with cathepsin E. Furthermore, cathepsin E expression increased with macrophage cultivation, which was positively correlated with an increased susceptibility to PRRSV infection. Together, these data show that, in macrophages, both the aspartic protease cathepsin E and an unidentified trypsin-like serine protease are involved in uncoating of internalized PRRSV and subsequent infection. porcine arterivirus / macrophage / virus entry / protease / receptor

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Involvement of proteases in porcine reproductive and respiratory syndrome virus uncoating upon internalization in primary macrophages

2008

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“…This receptor is restricted to cells of the porcine monocyte/macrophage lineage and more specifically, to macrophages and tissue DC [53] and confers susceptibility to PRRSV [43]. CD163…”

Section: Cd163mentioning

confidence: 99%

Membrane markers of the immune cells in swine: an update

Piriou-Guzylack¹,

2008

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-Besides their breeding value, swine are increasingly used as biomedical models. As reported in three international swine clusters of differentiation (CD) workshops and in the animal homologue section of the last workshop for the determination of human leukocyte differentiation antigens (HLDA 8), characterisation of leukocyte surface antigens by monoclonal antibodies and other molecular studies have determined the cell lineages and blood leukocyte subsets implicated in the immune response, including cell adhesion molecules involved in cell trafficking. This review focusses on the current state of knowledge of porcine leukocyte differentiation and major histocompatibility complex (SLA) molecules. Examples of porcine particularities such as the double-positive T lymphocytes with the phenotype CD4 + CD8 low and CD4 − CD8 low T cell subsets and the persistence of SLA class II after T-lymphocyte activation are illustrated, as well as the shared characteristics of the Artiodactyla group, such as the high proportion of TcR (T cell receptor) T cells in blood and other lymphoid tissues. Furthermore, discrepancies between swine and humans, such as CD16 expression on dendritic cells and CD11b (wCD11R1) tissue distribution are outlined. The rapidly growing information should facilitate manipulation of the swine immune system towards improving disease control, and open new avenues for biomedical research using the pig as a model. cluster of differentiation (CD) / monoclonal antibody / immune system / histocompatibility system / pig

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“…Signaling through CD163 can, in turn, lead to the secretion of high levels of IL-10 in macrophages, resulting in a positive feedback loop (Philippidis et al, 2004). In this respect, the interaction of PRRSV with CD163 recently reported by Calvert et al (2007) might play a role in the increased levels of IL-10 in PRRS.…”

Section: Discussionmentioning

confidence: 99%

“…In swine, we reported a role for CD163 in African swine fever (ASF) virus infection of monocyte/macrophage (Sánchez-Torres et al, 2003). Recently, Calvert et al (2007) have shown that expression of CD163 made cells susceptible to porcine respiratory and reproductive syndrome (PRRS) virus infection.…”

Section: Discussionmentioning

confidence: 99%

Cloning and expression of porcine CD163: its use for characterization of monoclonal antibodies to porcine CD163 and development of an ELISA to measure soluble CD163 in biological fluids

Pérez¹,

Ezquerra²,

Ortuño³

et al. 2008

Span. j. agric. res.

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CD163 is a member of the family of proteins with scavenger receptor cysteine-rich domains, whose expression is restricted to monocytes and macrophages. It functions as a receptor for haemoglobin/haptoglobin complexes and it has also been implicated in the regulation of inflammatory processes. Treatment of monocytes/macrophages with phorbol esters, LPS or cross-linking of Fc gamma receptors, causes shedding of CD163 from cell surface by a protease-dependent mechanism. The level of soluble CD163 (sCD163) in serum and other body fluids has been considered a useful marker of macrophage activation. In addition, porcine CD163 has been shown to play a role in the infection of monocytes/macrophages by the African swine fever virus. The porcine CD163 cDNA has been cloned, and expressed in transfected CHO cells. Clones of CHO cells stably expressing porcine CD163 have been used for the characterization of three new mAbs against porcine CD163. Using two of these mAbs, that bind to different epitopes on CD163 molecule, a sandwich enzyme-linked immunoassay (ELISA) has been developed to measure levels of sCD163 in porcine sera and biological fluids. The assay was calibrated using lysates of CD163 transfectants, showing a sensitivity of 10 5 cells mL -1 , that allowed to detect sCD163 in sera and in culture supernatants of activated alveolar macrophages. This assay can be a useful method of monitoring the degree of activation of macrophages in a variety of inflammatory and infectious diseases of swine.Additional key words: macrophage, SRCR family, swine. ResumenClonación y expresión de CD163 porcino: aplicación en la caracterización de anticuerpos monoclonales frente a CD163 porcino, y desarrollo de un ELISA para cuantificar CD163 soluble en fluidos biológicos CD163 es un miembro de la familia de proteínas con dominios de receptores «scavenger» ricos en cisteína, con una expresión restringida a células del linaje monocítico. Se ha demostrado su función como receptor de complejos hemoglobina/haptoglobina, y se le ha implicado en la regulación de procesos inflamatorios. El tratamiento de monocitos/macrófagos con ésteres de forbol, LPS, o mediante entrecruzamiento de receptores Fc gamma, provoca la liberación de CD163 de la superficie celular por un mecanismo dependiente de proteasas. La cantidad de CD163 soluble (sCD163) en suero y otros fluidos corporales se considera un indicador de la activación de los macrófagos. Recientemente, nuestro grupo demostró que CD163 está implicado en la infección de monocitos/macrófagos porcinos por el virus de la peste porcina africana. En este trabajo se describe la clonación del cDNA de CD163 porcino, y su expresión en células CHO transfectadas. Se obtuvieron clones de células CHO transfectadas que expresan de forma estable la molécula CD163 porcina, y se utilizaron para caracterizar tres nuevos anticuerpos monoclonales que reconocen específicamente CD163 porcino. El uso de dos de estos anticuerpos, que reconocen epítopos diferentes en CD163 porcino, ha permitido desarrollar un ensayo i...

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CD163 Expression Confers Susceptibility to Porcine Reproductive and Respiratory Syndrome Viruses

Cited by 295 publications

References 34 publications

Involvement of proteases in porcine reproductive and respiratory syndrome virus uncoating upon internalization in primary macrophages

Involvement of proteases in porcine reproductive and respiratory syndrome virus uncoating upon internalization in primary macrophages

Membrane markers of the immune cells in swine: an update

Cloning and expression of porcine CD163: its use for characterization of monoclonal antibodies to porcine CD163 and development of an ELISA to measure soluble CD163 in biological fluids

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