PMID- 35506985
OWN - NLM
STAT- MEDLINE
DCOM- 20220506
LR  - 20220531
IS  - 1465-2099 (Electronic)
IS  - 0022-1317 (Linking)
VI  - 103
IP  - 5
DP  - 2022 May
TI  - Mutations within scavenger receptor cysteine-rich (SRCR) protein domain 5 of 
      porcine CD163 involved in infection with porcine reproductive and respiratory 
      syndrome virus (PRRS).
LID - 10.1099/jgv.0.001740 [doi]
AB  - CD163, a macrophage-specific membrane scavenger receptor, serves as a cellular 
      entry receptor for porcine reproductive and respiratory syndrome virus (PRRSV). 
      The removal of scavenger receptor cysteine-rich (SRCR) domain 5 (SRCR5) of CD163 
      is sufficient to make transfected cells or genetically modified pigs resistant to 
      PRRSV-1 and PRRSV-2 genotypes, and substitution of SRCR5 with SRCR8 from human 
      CD163-like protein (hCD163L1) confers resistance to PRRSV-1 but not PRRSV-2 
      isolates. However, the specific regions within the SRCR5 polypeptide involved in 
      PRRSV infection remain largely unknown. In this report, we performed mutational 
      studies in order to identify which regions or amino acid sequences in the SRCR5 
      domain are critical for PRRSV infection. The approach used in this study was to 
      make proline-arginine (PR) insertions along the SRCR5 polypeptide. Constructs 
      were transfected into HEK293T cells, and then evaluated for infection with 
      PRRSV-2 or PRRSV-1. For PRRSV-2, four PR insertions located after amino acids 8 
      (PR-9), 47 (PR-48), 54 (PR-55), and 99 (PR-100) had the greatest impact on 
      infection. For PRRSV-1, insertions after amino acids 57 (PR-58) and 99 (PR-100) 
      were critical. Computer simulations based on the crystal structure of SRCR5 
      showed that the mutations that affected infection localized to a similar region 
      on the surface of the 3-D structure. Specifically, we found two surface patches 
      that are essential for PRRSV infection. PR-58 and PR-55, which were separated by 
      only three amino acids, had reciprocal effects on PRRSV-1 and PRRSV-2. 
      Substitution of Glu-58 with Lys-58 reduced PRRSV-1 infection without affecting 
      PRRSV-2, which partially explains the resistance to PRRSV-1 caused by the SRCR5 
      replacement with the homolog human SRCR8 previously observed. Finally, resistance 
      to infection was observed following the disruption of any of the four conserved 
      disulfide bonds within SRCR5. In summary, the results confirm that there are 
      distinct differences between PRRSV-1 and PRRSV-2 on recognition of CD163; 
      however, all mutations that affect infection locate on a similar region on the 
      same face of SRCR5.
FAU - Stoian, Ana M M
AU  - Stoian AMM
AD  - School of Medicine, Department of Medial Microbiology and Immunology, University 
      of California Davis, Davis, CA, USA.
FAU - Rowland, Raymond R R
AU  - Rowland RRR
AD  - Department of Pathobiology, College of Veterinary Medicine, University of 
      Illinois at Urbana-Champaign, Urbana, Illinois, USA.
FAU - Brandariz-Nunez, Alberto
AU  - Brandariz-Nunez A
AD  - Department of Pathobiology, College of Veterinary Medicine, University of 
      Illinois at Urbana-Champaign, Urbana, Illinois, USA.
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Gen Virol
JT  - The Journal of general virology
JID - 0077340
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CD163 antigen)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Scavenger)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Animals
MH  - Antigens, CD
MH  - Antigens, Differentiation, Myelomonocytic/genetics/metabolism
MH  - Cysteine/genetics
MH  - HEK293 Cells
MH  - Humans
MH  - Mutation
MH  - *Porcine Reproductive and Respiratory Syndrome/genetics
MH  - *Porcine respiratory and reproductive syndrome virus/genetics/metabolism
MH  - Protein Domains
MH  - Receptors, Cell Surface
MH  - Receptors, Scavenger/genetics
MH  - Swine
OTO - NOTNLM
OT  - CD163
OT  - PRRSV
OT  - SRCR5 domain
EDAT- 2022/05/05 06:00
MHDA- 2022/05/07 06:00
CRDT- 2022/05/04 10:53
PHST- 2022/05/04 10:53 [entrez]
PHST- 2022/05/05 06:00 [pubmed]
PHST- 2022/05/07 06:00 [medline]
AID - 10.1099/jgv.0.001740 [doi]
PST - ppublish
SO  - J Gen Virol. 2022 May;103(5). doi: 10.1099/jgv.0.001740.