Structural Studies on the Shapeshifting Murine Norovirus

Noroviruses are responsible for almost a fifth of all cases of gastroenteritis worldwide. The calicivirus capsid is composed of 180 copies of VP1 with a molecular weight of ~58 kDa. This coat protein is divided into the N-terminus (N), the shell (S) and C-terminal protruding (P) domains. The S domai...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Michael B. Sherman, Alexis N. Williams, Hong Q. Smith, B. Montgomery Pettitt, Christiane E. Wobus, Thomas J. Smith
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	norovirus antibodies bile neutralization Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/05de2b4e581245df82b16756955a039b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:05de2b4e581245df82b16756955a039b
record_format	dspace
spelling	oai:doaj.org-article:05de2b4e581245df82b16756955a039b2021-11-25T19:12:56ZStructural Studies on the Shapeshifting Murine Norovirus10.3390/v131121621999-4915https://doaj.org/article/05de2b4e581245df82b16756955a039b2021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2162https://doaj.org/toc/1999-4915Noroviruses are responsible for almost a fifth of all cases of gastroenteritis worldwide. The calicivirus capsid is composed of 180 copies of VP1 with a molecular weight of ~58 kDa. This coat protein is divided into the N-terminus (N), the shell (S) and C-terminal protruding (P) domains. The S domain forms a shell around the viral RNA genome, while the P domains dimerize to form protrusions on the capsid surface. The P domain is subdivided into P1 and P2 subdomains, with the latter containing the binding sites for cellular receptors and neutralizing antibodies. Reviewed here are studies on murine norovirus (MNV) showing that the capsid responds to several physiologically relevant cues; bile, pH, Mg<sup>2+</sup>, and Ca<sup>2+</sup>. In the initial site of infection, the intestinal tract, high bile and metal concentrations and low pH cause two significant conformational changes: (1) the P domain contracts onto the shell domain and (2) several conformational changes within the P domain lead to enhanced receptor binding while blocking antibody neutralization. In contrast, the pH is neutral, and the concentrations of bile and metals are low in the serum. Under these conditions, the loops at the tip of the P domain are in the open conformation with the P domain floating on a linker or tether above the shell. This conformational state favors antibody binding but reduces interactions with the receptor. In this way, MNV uses metabolites and environmental cues in the intestine to optimize cellular attachment and escape antibody binding but presents a wholly different structure to the immune system in the serum. To our knowledge, this is the first example of a virus shapeshifting in this manner to escape the immune response.Michael B. ShermanAlexis N. WilliamsHong Q. SmithB. Montgomery PettittChristiane E. WobusThomas J. SmithMDPI AGarticlenorovirusantibodiesbileneutralizationMicrobiologyQR1-502ENViruses, Vol 13, Iss 2162, p 2162 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	norovirus antibodies bile neutralization Microbiology QR1-502
spellingShingle	norovirus antibodies bile neutralization Microbiology QR1-502 Michael B. Sherman Alexis N. Williams Hong Q. Smith B. Montgomery Pettitt Christiane E. Wobus Thomas J. Smith Structural Studies on the Shapeshifting Murine Norovirus
description	Noroviruses are responsible for almost a fifth of all cases of gastroenteritis worldwide. The calicivirus capsid is composed of 180 copies of VP1 with a molecular weight of ~58 kDa. This coat protein is divided into the N-terminus (N), the shell (S) and C-terminal protruding (P) domains. The S domain forms a shell around the viral RNA genome, while the P domains dimerize to form protrusions on the capsid surface. The P domain is subdivided into P1 and P2 subdomains, with the latter containing the binding sites for cellular receptors and neutralizing antibodies. Reviewed here are studies on murine norovirus (MNV) showing that the capsid responds to several physiologically relevant cues; bile, pH, Mg<sup>2+</sup>, and Ca<sup>2+</sup>. In the initial site of infection, the intestinal tract, high bile and metal concentrations and low pH cause two significant conformational changes: (1) the P domain contracts onto the shell domain and (2) several conformational changes within the P domain lead to enhanced receptor binding while blocking antibody neutralization. In contrast, the pH is neutral, and the concentrations of bile and metals are low in the serum. Under these conditions, the loops at the tip of the P domain are in the open conformation with the P domain floating on a linker or tether above the shell. This conformational state favors antibody binding but reduces interactions with the receptor. In this way, MNV uses metabolites and environmental cues in the intestine to optimize cellular attachment and escape antibody binding but presents a wholly different structure to the immune system in the serum. To our knowledge, this is the first example of a virus shapeshifting in this manner to escape the immune response.
format	article
author	Michael B. Sherman Alexis N. Williams Hong Q. Smith B. Montgomery Pettitt Christiane E. Wobus Thomas J. Smith
author_facet	Michael B. Sherman Alexis N. Williams Hong Q. Smith B. Montgomery Pettitt Christiane E. Wobus Thomas J. Smith
author_sort	Michael B. Sherman
title	Structural Studies on the Shapeshifting Murine Norovirus
title_short	Structural Studies on the Shapeshifting Murine Norovirus
title_full	Structural Studies on the Shapeshifting Murine Norovirus
title_fullStr	Structural Studies on the Shapeshifting Murine Norovirus
title_full_unstemmed	Structural Studies on the Shapeshifting Murine Norovirus
title_sort	structural studies on the shapeshifting murine norovirus
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/05de2b4e581245df82b16756955a039b
work_keys_str_mv	AT michaelbsherman structuralstudiesontheshapeshiftingmurinenorovirus AT alexisnwilliams structuralstudiesontheshapeshiftingmurinenorovirus AT hongqsmith structuralstudiesontheshapeshiftingmurinenorovirus AT bmontgomerypettitt structuralstudiesontheshapeshiftingmurinenorovirus AT christianeewobus structuralstudiesontheshapeshiftingmurinenorovirus AT thomasjsmith structuralstudiesontheshapeshiftingmurinenorovirus
_version_	1718410134156214272

Structural Studies on the Shapeshifting Murine Norovirus

Ejemplares similares