An Intact Sialoadhesin (Sn/SIGLEC1/CD169) Is Not Required for Attachment/Internalization of the Porcine Reproductive and Respiratory Syndrome Virus

Abstract

bSurface expression of SIGLEC1, also known as sialoadhesin or CD169, is considered a primary determinant of the permissiveness of porcine alveolar macrophages for infection by porcine reproductive and respiratory syndrome virus (PRRSV). In vitro, the attachment and internalization of PRRSV are dependent on the interaction between sialic acid on the virion surface and the sialic acid binding domain of the SIGLEC1 gene. To test the role of SIGLEC1 in PRRSV infection, a SIGLEC1 gene knockout pig was created by removing part of exon 1 and all of exons 2 and 3 of the SIGLEC1 gene. The resulting knockout ablated SIGLEC1 expression on the surface of alveolar macrophages but had no effect on the expression of CD163, a coreceptor for PRRSV. After infection, PRRSV viremia in SIGLEC1 ؊/؊ pigs followed the same course as in SIGLEC1 ؊/؉ and SIGLEC1 ؉/؉ littermates. The absence of SIGLEC1 had no measurable effect on other aspects of PRRSV infection, including clinical disease course and histopathology. The results demonstrate that the expression of the SIGLEC1 gene is not required for infection of pigs with PRRSV and that the absence of SIGLEC1 does not contribute to the pathogenesis of acute disease.

Replacement of Porcine CD163 Scavenger Receptor Cysteine-Rich Domain 5 with a CD163-Like Homolog Confers Resistance of Pigs to Genotype 1 but Not Genotype 2 Porcine Reproductive and Respiratory Syndrome Virus

“…of wild-type pigs after infection with a type 2 virus (14). These results supported previous in vitro studies showing that PRRSV-resistant cell lines lacking surface CD169 and CD163 supported virus replication after transfection with a CD163 plasmid (15).…”

“…Staining for surface expression of CD169 and CD163 was performed as described previously (14). Measurement of PRRS viremia.…”

The Crystal Structure of the Fifth Scavenger Receptor Cysteine-Rich Domain of Porcine CD163 Reveals an Important Residue Involved in Porcine Reproductive and Respiratory Syndrome Virus Infection

“…However, one study showed that Sn gene knockout pigs were infected by PRRSV as usual (49), and a recent study using geneedited pigs demonstrates the indispensability of pCD163 (28). Therefore, pCD163 is a core receptor for PRRSV infection and requires more in-depth research.…”

Mouse Siglec-1 Mediates trans-Infection of Surface-bound Murine Leukemia Virus in a Sialic Acid N-Acyl Side Chain-dependent Manner

“…Earlier work indicated a role of Siglec-1 as a receptor for infection of alveolar macrophages by porcine reproductive and respiratory syndrome virus. However, this was called into question in a study using Siglec-1 KO pigs (12). Both human and mouse Siglec-1 (mSiglec-1) expressed on human cells were recently shown to capture ecotropic murine leukemia virus (MLV), a simple retrovirus and mouse pathogen, in a ganglioside-dependent manner (13).…”