Natural killer cell dependent within-host competition arises during multiple MCMV infection: consequences for viral transmission and evolution.

It is becoming increasingly clear that many diseases are the result of infection from multiple genetically distinct strains of a pathogen. Such multi-strain infections have the capacity to alter both disease and pathogen dynamics. Infection with multiple strains of human cytomegalovirus (HCMV) is co...

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Autores principales:	Andrea R McWhorter, Lee M Smith, Laura L Masters, Baca Chan, Geoffrey R Shellam, Alec J Redwood
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/2c1058716fd949ec952a544d9e165b4b
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spelling	oai:doaj.org-article:2c1058716fd949ec952a544d9e165b4b2021-11-18T06:06:11ZNatural killer cell dependent within-host competition arises during multiple MCMV infection: consequences for viral transmission and evolution.1553-73661553-737410.1371/journal.ppat.1003111https://doaj.org/article/2c1058716fd949ec952a544d9e165b4b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300458/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374It is becoming increasingly clear that many diseases are the result of infection from multiple genetically distinct strains of a pathogen. Such multi-strain infections have the capacity to alter both disease and pathogen dynamics. Infection with multiple strains of human cytomegalovirus (HCMV) is common and has been linked to enhanced disease. Suggestions that disease enhancement in multi-strain infected patients is due to complementation have been supported by trans-complementation studies in mice during co-infection of wild type and gene knockout strains of murine CMV (MCMV). Complementation between naturally circulating strains of CMV has, however, not been assessed. In addition, many models of multi-strain infection predict that co-infecting strains will compete with each other and that this competition may contribute to selective transmission of more virulent pathogen strains. To assess the outcome of multi-strain infection, C57BL/6 mice were infected with up to four naturally circulating strains of MCMV. In this study, profound within-host competition was observed between co-infecting strains of MCMV. This competition was MCMV strain specific and resulted in the complete exclusion of certain strains of MCMV from the salivary glands of multi-strain infected mice. Competition was dependent on Ly49H(+) natural killer (NK) cells as well as the expression of the ligand for Ly49H, the MCMV encoded product, m157. Strains of MCMV which expressed an m157 gene product capable of ligating Ly49H were outcompeted by strains of MCMV expressing variant m157 genes. Importantly, within-host competition prevented the shedding of the less virulent strains of MCMV, those recognized by Ly49H, into the saliva of multi-strain infected mice. These data demonstrate that NK cells have the strain specific recognition capacity required to meditate within-host competition between strains of MCMV. Furthermore, this within-host competition has the capacity to shape the dynamics of viral shedding and potentially select for the transmission of more virulent virus strains.Andrea R McWhorterLee M SmithLaura L MastersBaca ChanGeoffrey R ShellamAlec J RedwoodPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 1, p e1003111 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Andrea R McWhorter Lee M Smith Laura L Masters Baca Chan Geoffrey R Shellam Alec J Redwood Natural killer cell dependent within-host competition arises during multiple MCMV infection: consequences for viral transmission and evolution.
description	It is becoming increasingly clear that many diseases are the result of infection from multiple genetically distinct strains of a pathogen. Such multi-strain infections have the capacity to alter both disease and pathogen dynamics. Infection with multiple strains of human cytomegalovirus (HCMV) is common and has been linked to enhanced disease. Suggestions that disease enhancement in multi-strain infected patients is due to complementation have been supported by trans-complementation studies in mice during co-infection of wild type and gene knockout strains of murine CMV (MCMV). Complementation between naturally circulating strains of CMV has, however, not been assessed. In addition, many models of multi-strain infection predict that co-infecting strains will compete with each other and that this competition may contribute to selective transmission of more virulent pathogen strains. To assess the outcome of multi-strain infection, C57BL/6 mice were infected with up to four naturally circulating strains of MCMV. In this study, profound within-host competition was observed between co-infecting strains of MCMV. This competition was MCMV strain specific and resulted in the complete exclusion of certain strains of MCMV from the salivary glands of multi-strain infected mice. Competition was dependent on Ly49H(+) natural killer (NK) cells as well as the expression of the ligand for Ly49H, the MCMV encoded product, m157. Strains of MCMV which expressed an m157 gene product capable of ligating Ly49H were outcompeted by strains of MCMV expressing variant m157 genes. Importantly, within-host competition prevented the shedding of the less virulent strains of MCMV, those recognized by Ly49H, into the saliva of multi-strain infected mice. These data demonstrate that NK cells have the strain specific recognition capacity required to meditate within-host competition between strains of MCMV. Furthermore, this within-host competition has the capacity to shape the dynamics of viral shedding and potentially select for the transmission of more virulent virus strains.
format	article
author	Andrea R McWhorter Lee M Smith Laura L Masters Baca Chan Geoffrey R Shellam Alec J Redwood
author_facet	Andrea R McWhorter Lee M Smith Laura L Masters Baca Chan Geoffrey R Shellam Alec J Redwood
author_sort	Andrea R McWhorter
title	Natural killer cell dependent within-host competition arises during multiple MCMV infection: consequences for viral transmission and evolution.
title_short	Natural killer cell dependent within-host competition arises during multiple MCMV infection: consequences for viral transmission and evolution.
title_full	Natural killer cell dependent within-host competition arises during multiple MCMV infection: consequences for viral transmission and evolution.
title_fullStr	Natural killer cell dependent within-host competition arises during multiple MCMV infection: consequences for viral transmission and evolution.
title_full_unstemmed	Natural killer cell dependent within-host competition arises during multiple MCMV infection: consequences for viral transmission and evolution.
title_sort	natural killer cell dependent within-host competition arises during multiple mcmv infection: consequences for viral transmission and evolution.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/2c1058716fd949ec952a544d9e165b4b
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Natural killer cell dependent within-host competition arises during multiple MCMV infection: consequences for viral transmission and evolution.

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