PMID- 39048821
OWN - NLM
STAT- Publisher
LR  - 20240724
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Linking)
DP  - 2024 Jul 24
TI  - Shifts in receptors during submergence of an encephalitic arbovirus.
LID - 10.1038/s41586-024-07740-2 [doi]
AB  - Western equine encephalitis virus (WEEV) is an arthropod-borne virus (arbovirus) 
      that frequently caused major outbreaks of encephalitis in humans and horses in 
      the early twentieth century, but the frequency of outbreaks has since decreased 
      markedly, and strains of this alphavirus isolated in the past two decades are 
      less virulent in mammals than strains isolated in the 1930s and 1940s(1-3). The 
      basis for this phenotypic change in WEEV strains and coincident decrease in 
      epizootic activity (known as viral submergence(3)) is unclear, as is the 
      possibility of re-emergence of highly virulent strains. Here we identify 
      protocadherin 10 (PCDH10) as a cellular receptor for WEEV. We show that multiple 
      highly virulent ancestral WEEV strains isolated in the 1930s and 1940s, in 
      addition to binding human PCDH10, could also bind very low-density lipoprotein 
      receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2), which are recognized 
      by another encephalitic alphavirus as receptors(4). However, whereas most of the 
      WEEV strains that we examined bind to PCDH10, a contemporary strain has lost the 
      ability to recognize mammalian PCDH10 while retaining the ability to bind avian 
      receptors, suggesting WEEV adaptation to a main reservoir host during enzootic 
      circulation. PCDH10 supports WEEV E2-E1 glycoprotein-mediated infection of 
      primary mouse cortical neurons, and administration of a soluble form of PCDH10 
      protects mice from lethal WEEV challenge. Our results have implications for the 
      development of medical countermeasures and for risk assessment for re-emerging 
      WEEV strains.
CI  - © 2024. The Author(s).
FAU - Li, Wanyu
AU  - Li W
AUID- ORCID: 0000-0002-5964-1545
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
FAU - Plante, Jessica A
AU  - Plante JA
AUID- ORCID: 0000-0002-4768-7458
AD  - World Reference Center for Emerging Viruses and Arboviruses, University of Texas 
      Medical Branch, Galveston, TX, USA.
AD  - Department of Microbiology and Immunology, University of Texas Medical Branch, 
      Galveston, TX, USA.
AD  - Institute for Human Infections and Immunity, University of Texas Medical Branch, 
      Galveston, TX, USA.
FAU - Lin, ChieYu
AU  - Lin C
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
FAU - Basu, Himanish
AU  - Basu H
AUID- ORCID: 0000-0001-8236-1157
AD  - Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
FAU - Plung, Jesse S
AU  - Plung JS
AUID- ORCID: 0000-0003-1950-7031
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
FAU - Fan, Xiaoyi
AU  - Fan X
AUID- ORCID: 0009-0002-3181-9994
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
FAU - Boeckers, Joshua M
AU  - Boeckers JM
AD  - Department of Neurology, F. M. Kirby Neurobiology Center, Boston Children's 
      Hospital, Harvard Medical School, Boston, MA, USA.
FAU - Oros, Jessica
AU  - Oros J
AUID- ORCID: 0009-0004-9424-7289
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
FAU - Buck, Tierra K
AU  - Buck TK
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
FAU - Anekal, Praju V
AU  - Anekal PV
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
AD  - MicRoN Core, Harvard Medical School, Boston, MA, USA.
FAU - Hanson, Wesley A
AU  - Hanson WA
AUID- ORCID: 0000-0002-3627-3233
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
FAU - Varnum, Haley
AU  - Varnum H
AUID- ORCID: 0000-0001-8558-8007
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
FAU - Wells, Adrienne
AU  - Wells A
AUID- ORCID: 0000-0003-3372-5588
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
AD  - MicRoN Core, Harvard Medical School, Boston, MA, USA.
FAU - Mann, Colin J
AU  - Mann CJ
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
FAU - Tjang, Laurentia V
AU  - Tjang LV
AUID- ORCID: 0000-0003-0949-3713
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
FAU - Yang, Pan
AU  - Yang P
AUID- ORCID: 0000-0002-2431-0252
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
FAU - Reyna, Rachel A
AU  - Reyna RA
AUID- ORCID: 0000-0001-8421-8397
AD  - World Reference Center for Emerging Viruses and Arboviruses, University of Texas 
      Medical Branch, Galveston, TX, USA.
AD  - Department of Microbiology and Immunology, University of Texas Medical Branch, 
      Galveston, TX, USA.
AD  - Institute for Human Infections and Immunity, University of Texas Medical Branch, 
      Galveston, TX, USA.
FAU - Mitchell, Brooke M
AU  - Mitchell BM
AD  - World Reference Center for Emerging Viruses and Arboviruses, University of Texas 
      Medical Branch, Galveston, TX, USA.
AD  - Department of Microbiology and Immunology, University of Texas Medical Branch, 
      Galveston, TX, USA.
AD  - Institute for Human Infections and Immunity, University of Texas Medical Branch, 
      Galveston, TX, USA.
FAU - Shinde, Divya P
AU  - Shinde DP
AD  - World Reference Center for Emerging Viruses and Arboviruses, University of Texas 
      Medical Branch, Galveston, TX, USA.
AD  - Department of Microbiology and Immunology, University of Texas Medical Branch, 
      Galveston, TX, USA.
AD  - Institute for Human Infections and Immunity, University of Texas Medical Branch, 
      Galveston, TX, USA.
FAU - Walker, Jordyn L
AU  - Walker JL
AD  - World Reference Center for Emerging Viruses and Arboviruses, University of Texas 
      Medical Branch, Galveston, TX, USA.
AD  - Department of Microbiology and Immunology, University of Texas Medical Branch, 
      Galveston, TX, USA.
AD  - Institute for Human Infections and Immunity, University of Texas Medical Branch, 
      Galveston, TX, USA.
FAU - Choi, So Yoen
AU  - Choi SY
AD  - Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
FAU - Brusic, Vesna
AU  - Brusic V
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
FAU - Llopis, Paula Montero
AU  - Llopis PM
AUID- ORCID: 0000-0002-5983-2296
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
AD  - MicRoN Core, Harvard Medical School, Boston, MA, USA.
FAU - Weaver, Scott C
AU  - Weaver SC
AUID- ORCID: 0000-0001-8016-8556
AD  - World Reference Center for Emerging Viruses and Arboviruses, University of Texas 
      Medical Branch, Galveston, TX, USA.
AD  - Department of Microbiology and Immunology, University of Texas Medical Branch, 
      Galveston, TX, USA.
AD  - Institute for Human Infections and Immunity, University of Texas Medical Branch, 
      Galveston, TX, USA.
FAU - Umemori, Hisashi
AU  - Umemori H
AUID- ORCID: 0000-0001-7198-2062
AD  - Department of Neurology, F. M. Kirby Neurobiology Center, Boston Children's 
      Hospital, Harvard Medical School, Boston, MA, USA.
FAU - Chiu, Isaac M
AU  - Chiu IM
AUID- ORCID: 0000-0002-0723-4841
AD  - Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA.
FAU - Plante, Kenneth S
AU  - Plante KS
AUID- ORCID: 0000-0002-7485-3167
AD  - World Reference Center for Emerging Viruses and Arboviruses, University of Texas 
      Medical Branch, Galveston, TX, USA.
AD  - Department of Microbiology and Immunology, University of Texas Medical Branch, 
      Galveston, TX, USA.
AD  - Institute for Human Infections and Immunity, University of Texas Medical Branch, 
      Galveston, TX, USA.
FAU - Abraham, Jonathan
AU  - Abraham J
AUID- ORCID: 0000-0002-7937-3920
AD  - Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, 
      MA, USA. jonathan_abraham@hms.harvard.edu.
AD  - Department of Medicine, Division of Infectious Diseases, Brigham and Women's 
      Hospital, Boston, MA, USA. jonathan_abraham@hms.harvard.edu.
AD  - Center for Integrated Solutions in Infectious Diseases, Broad Institute of 
      Harvard and MIT, Cambridge, MA, USA. jonathan_abraham@hms.harvard.edu.
LA  - eng
PT  - Journal Article
DEP - 20240724
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
SB  - IM
EDAT- 2024/07/26 12:36
MHDA- 2024/07/26 12:36
CRDT- 2024/07/24 23:30
PHST- 2024/01/05 00:00 [received]
PHST- 2024/06/19 00:00 [accepted]
PHST- 2024/07/26 12:36 [medline]
PHST- 2024/07/26 12:36 [pubmed]
PHST- 2024/07/24 23:30 [entrez]
AID - 10.1038/s41586-024-07740-2 [pii]
AID - 10.1038/s41586-024-07740-2 [doi]
PST - aheadofprint
SO  - Nature. 2024 Jul 24. doi: 10.1038/s41586-024-07740-2.