TY - JOUR
T1 - CD164 is a host factor for lymphocytic choriomeningitis virus entry
AU - Bakkers, Mark J.G.
AU - Moon-Walker, Alex
AU - Herlo, Rasmus
AU - Brusic, Vesna
AU - Stubbs, Sarah Hulsey
AU - Hastie, Kathryn M.
AU - Saphire, Erica Ollmann
AU - Kirchhausen, Tomas L.
AU - Whelan, Sean P.J.
N1 - Funding Information:
We gratefully acknowledge the expert support of the Harvard Medical School Flow Cytometry Core and the MicRoN imaging core. We thank Juan Carlos de la Torre (Scripps) for LCMV-2A-GFP and Nir Hacohen (Broad Institute of Massachusetts Institute of Technology and Harvard) for provision of A549-Cas9 cells. We also thank members of the S.P.J.W. laboratory for extensive discussions. Funding was provided by the following grants: NIH Grant U19-AI109740 (S.P.J.W.), NIH Grant T32-AI007245 (S.P.J.W.), and NIH Grant F31-AI154700 (A.M.-W.).
Funding Information:
ACKNOWLEDGMENTS. We gratefully acknowledge the expert support of the Harvard Medical School Flow Cytometry Core and the MicRoN imaging core. We thank Juan Carlos de la Torre (Scripps) for LCMV-2A-GFP and Nir Hacohen (Broad Institute of Massachusetts Institute of Technology and Harvard) for provision of A549-Cas9 cells. We also thank members of the S.P.J.W. laboratory for extensive discussions. Funding was provided by the following grants: NIH Grant U19-AI109740 (S.P.J.W.), NIH Grant T32-AI007245 (S.P.J.W.), and NIH Grant F31-AI154700 (A.M.-W.).
Publisher Copyright:
© 2022 National Academy of Sciences. All rights reserved.
PY - 2022/3/8
Y1 - 2022/3/8
N2 - Lymphocytic choriomeningitis virus (LCMV) is a rodent-borne zoonotic arenavirus that causes congenital abnormalities and can be fatal for transplant recipients. Using a genome-wide loss-of-function screen, we identify host factors required for LCMV entry into cells. We identify the lysosomal mucin CD164, glycosylation factors, the heparan sulfate biosynthesis machinery, and the known receptor alpha-dystroglycan (α-DG). Biochemical analysis revealed that the LCMV glycoprotein binds CD164 at acidic pH and requires a sialylated glycan at residue N104. We demonstrate that LCMV entry proceeds by the virus switching binding from heparan sulfate or α-DG at the plasma membrane to CD164 prior to membrane fusion, thus identifying additional potential targets for therapeutic intervention.
AB - Lymphocytic choriomeningitis virus (LCMV) is a rodent-borne zoonotic arenavirus that causes congenital abnormalities and can be fatal for transplant recipients. Using a genome-wide loss-of-function screen, we identify host factors required for LCMV entry into cells. We identify the lysosomal mucin CD164, glycosylation factors, the heparan sulfate biosynthesis machinery, and the known receptor alpha-dystroglycan (α-DG). Biochemical analysis revealed that the LCMV glycoprotein binds CD164 at acidic pH and requires a sialylated glycan at residue N104. We demonstrate that LCMV entry proceeds by the virus switching binding from heparan sulfate or α-DG at the plasma membrane to CD164 prior to membrane fusion, thus identifying additional potential targets for therapeutic intervention.
KW - CD164
KW - arenavirus
KW - lymphocytic choriomeningitis virus
KW - virus entry
UR - http://www.scopus.com/inward/record.url?scp=85125614529&partnerID=8YFLogxK
U2 - 10.1073/pnas.2119676119
DO - 10.1073/pnas.2119676119
M3 - Article
C2 - 35235462
AN - SCOPUS:85125614529
VL - 119
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 10
M1 - e2119676119
ER -