Discrete viral E2 lysine residues and scavenger receptor MARCO are required for clearance of circulating alphaviruses.
alphavirus
arbovirus
infectious disease
innate immunity
microbiology
mouse
scavenger receptor
virus
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
09 10 2019
09 10 2019
Historique:
received:
07
06
2019
accepted:
04
10
2019
pubmed:
10
10
2019
medline:
12
3
2020
entrez:
10
10
2019
Statut:
epublish
Résumé
The magnitude and duration of vertebrate viremia is a critical determinant of arbovirus transmission, geographic spread, and disease severity. We find that multiple alphaviruses, including chikungunya (CHIKV), Ross River (RRV), and o'nyong 'nyong (ONNV) viruses, are cleared from the circulation of mice by liver Kupffer cells, impeding viral dissemination. Clearance from the circulation was independent of natural antibodies or complement factor C3, and instead relied on scavenger receptor SR-A6 (MARCO). Remarkably, lysine to arginine substitutions at distinct residues within the E2 glycoproteins of CHIKV and ONNV (E2 K200R) as well as RRV (E2 K251R) allowed for escape from clearance and enhanced viremia and dissemination. Mutational analysis revealed that viral clearance from the circulation is strictly dependent on the presence of lysine at these positions. These findings reveal a previously unrecognized innate immune pathway that controls alphavirus viremia and dissemination in vertebrate hosts, ultimately influencing disease severity and likely transmission efficiency.
Identifiants
pubmed: 31596239
doi: 10.7554/eLife.49163
pii: 49163
pmc: PMC6839921
doi:
pii:
Substances chimiques
Marco protein, mouse
0
Receptors, Immunologic
0
Viral Envelope Proteins
0
Lysine
K3Z4F929H6
Banques de données
GEO
['GSE109774']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : F32 AI140567
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI123348
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI052066
Pays : United States
Informations de copyright
© 2019, Carpentier et al.
Déclaration de conflit d'intérêts
KC, BD, KH, MM, NM, AR, CR, GE, TM No competing interests declared
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