Molecular cloning of porcine Siglec-3, Siglec-5 and Siglec-10, and identification of Siglec-10 as an alternative receptor for porcine reproductive and respiratory syndrome virus (PRRSV)

Abstract

In recent years, several entry mediators have been characterized for porcine reproductive and respiratory syndrome virus (PRRSV). Porcine sialoadhesin [pSn, also known as sialic acid-binding immunoglobulin-type lectin (Siglec-1)] and porcine CD163 (pCD163) have been identified as the most important host entry mediators that can fully coordinate PRRSV infection into macrophages. However, recent isolates have not only shown a tropism for sialoadhesin-positive cells, but also for sialoadhesin-negative cells. This observation might be partly explained by the existence of additional receptors that can support PRRSV binding and entry. In the search for new receptors, recently identified porcine Siglecs (Siglec-3, Siglec-5 and Siglec-10), members of the same family as sialoadhesin, were cloned and characterized. Only Siglec-10 was able to significantly improve PRRSV infection and production in a CD163-transfected cell line. Compared with sialoadhesin, Siglec-10 performed equally effectively as a receptor for PRRSV type 2 strain MN-184, but it was less capable of supporting infection with PRRSV type 1 strain LV (Lelystad virus). Siglec-10 was demonstrated to be involved in the endocytosis of PRRSV, confirming the important role of Siglec-10 in the entry process of PRRSV. In conclusion, it can be stated that PRRSV may use several Siglecs to enter macrophages, which may explain the strain differences in the pathogenesis.

Siglecs at the Host–Pathogen Interface

“…Siglec-10 showed a higher affinity to type 2 PRRSV vs. type 1 PRRSV and mediates attachment and endocytosis of PRRSV in a Sia-dependent manner, while transfection of Siglec-10 into non-permissive cells also restored the PRRSV infectivity. These findings indicate that PRRSV can use several Siglecs to enter macrophages and may influence strain differences in pathogenesis (Xie et al 2017). Of note, PRRSV lung infection induces minimal production of type I interferon and inflammatory cytokines compared to infections caused by swine influenza virus and porcine respiratory coronavirus (Van Reeth et al 1999).…”

“…Although Siglec-1 and CD163 are general recognized as the key entry mediators for PRRSV infection, a recent report demonstrated that certain PRRSV strains can infect Siglec-1-deficient cells by exploiting Siglec-10 in the presence of CD163 (Frydas and Nauwynck 2016; Xie et al 2017). Siglec-10 showed a higher affinity to type 2 PRRSV vs. type 1 PRRSV and mediates attachment and endocytosis of PRRSV in a Sia-dependent manner, while transfection of Siglec-10 into non-permissive cells also restored the PRRSV infectivity.…”

Serine 105 and 120 are important phosphorylation sites for porcine reproductive and respiratory syndrome virus N protein function

“…PRRSV, lactate dehydrogenase-elevating virus (LDV), simian hemorrhagic fever virus (SHFV), and equine arteritis virus (EAV) are members of family Arteriviridae. PRRSV has two types: the EU type and the NA type (Xie et al, 2017). PRRSV contains 14 non-structural proteins and 7 structural proteins .…”

Characterization of the attachment and infection by Porcine reproductive and respiratory syndrome virus 1 isolates in bone marrow-derived dendritic cells

“…Recently, Xie et al (2017) showed that siglec-10 was an efficient receptor for PRRSV2 but less capable of supporting the infection by PRRSV1. Apart from the affinity of different isolates to different receptors, alternative entry pathways not driven by the receptor-ligand interaction might exist.…”