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Discrete viral E2 lysine residues and scavenger receptor MARCO are required for clearance of circulating alphaviruses.
- Source :
-
ELife [Elife] 2019 Oct 09; Vol. 8. Date of Electronic Publication: 2019 Oct 09. - Publication Year :
- 2019
-
Abstract
- 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.<br />Competing Interests: KC, BD, KH, MM, NM, AR, CR, GE, TM No competing interests declared<br /> (© 2019, Carpentier et al.)
- Subjects :
- Animals
Disease Models, Animal
Lysine genetics
Lysine metabolism
Mice
Mutation, Missense
Alphavirus Infections immunology
Chikungunya virus immunology
Kupffer Cells immunology
O'nyong-nyong Virus immunology
Receptors, Immunologic metabolism
Viral Envelope Proteins genetics
Viral Envelope Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 31596239
- Full Text :
- https://doi.org/10.7554/eLife.49163