Recent Advances in PRRS Virus Receptors and the Targeting of Receptor-Ligand for Control

Abstract

Cellular receptors play a critical role in viral infection. At least seven cellular molecules have been identified as putative viral entry mediators for porcine reproductive and respiratory syndrome virus (PRRSV). Accumulating data indicate that among these candidates, CD163, a cysteine-rich scavenger receptor on macrophages, is the major receptor for PRRSV. This review discusses the recent advances and understanding of the entry of PRRSV into cells, viral pathogenesis in CD163 gene-edited swine, and CD163 as a potential target of receptor-ligand for the control of PRRS.

Keywords: CD163; PRRSV; porcine reproductive and respiratory syndrome; receptor.

Figure 1

Structure of porcine CD163, human CD163, human CD163L1, and their supportability for porcine reproductive and respiratory syndrome virus (PRRSV)-1 or PRRSV-2 infection. Porcine CD163 supports PRRSV-1 and PRRSV-2 infections, whereas human CD163 supports PRRSV-2 infection [32]. Whether human CD163 supports PRRSV-1 infection is unknown. Human CD163L1 is a homolog of CD163 but does not support PRRSV-1 infection [94]. The cysteine-rich scavenger receptor superfamily (SRCR)5-swap CD163 was made by replacing the SRCR5 domain of porcine CD163 with the SRCR8 domain of human CD163L1. Expression of SRCR5-swap CD163 in HEK293T (human embryonic kidney cells) and porcine alveolar macrophages (PAMs) does not confer the permissiveness of PRRSV-1 [94,98]. However, SRCR5-swap CD163 in PAMs supports most PRRSV-2 strains infection [98], except PRRSV-2 JXA1 [99].

Figure 2

The gene-edited swine with CD163-KO or SRCR5-swap CD163 were tested for the permissiveness of different strains of PRRSV. (a) All strains of PRRSV-1 and PRRSV-2 can infect wild-type pigs; (b) after knockout CD163, swine were resistant to PRRSV-1 (SD16-15, Lelystad, 03-1059, 03-1060, SD01-08, 4353-PZ [98], H2, DAI, SU1-Bel [114], BOR-57 [38]) and PRRSV-2 (NVSL 97, KS-06, P129, VR2332, CO90, CO84, MLV-ResP, KS62, KS483 [98], TP [39], JXA1 [40], MY [41]); (c) SRCR5-swap CD163 swine were resistant to PRRSV-1 (SD16-15, Lelystad, 03-1059, 03-1060, SD01-08, 4353-PZ) [98]; however, these swine still minimally allowed PRRSV-2 infection (NVSL 97, KS-06, P129, VR2332, CO90, CO84, MLV-ResP, KS62, KS483) [98].