Predominant infection of CD150+ lymphocytes and dendritic cells during measles virus infection of macaques.

Measles virus (MV) is hypothesized to enter the host by infecting epithelial cells of the respiratory tract, followed by viremia mediated by infected monocytes. However, neither of these cell types express signaling lymphocyte activation molecule (CD150), which has been identified as the receptor fo...

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Main Authors: Rik L de Swart, Martin Ludlow, Lot de Witte, Yusuke Yanagi, Geert van Amerongen, Stephen McQuaid, Selma Yüksel, Teunis B H Geijtenbeek, W Paul Duprex, Albert D M E Osterhaus
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2007-11-01
Series:PLoS Pathogens
Online Access:https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.0030178&type=printable
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author Rik L de Swart
Martin Ludlow
Lot de Witte
Yusuke Yanagi
Geert van Amerongen
Stephen McQuaid
Selma Yüksel
Teunis B H Geijtenbeek
W Paul Duprex
Albert D M E Osterhaus
author_facet Rik L de Swart
Martin Ludlow
Lot de Witte
Yusuke Yanagi
Geert van Amerongen
Stephen McQuaid
Selma Yüksel
Teunis B H Geijtenbeek
W Paul Duprex
Albert D M E Osterhaus
author_sort Rik L de Swart
collection DOAJ
description Measles virus (MV) is hypothesized to enter the host by infecting epithelial cells of the respiratory tract, followed by viremia mediated by infected monocytes. However, neither of these cell types express signaling lymphocyte activation molecule (CD150), which has been identified as the receptor for wild-type MV. We have infected rhesus and cynomolgus macaques with a recombinant MV strain expressing enhanced green fluorescent protein (EGFP); thus bringing together the optimal animal model for measles and a virus that can be detected with unprecedented sensitivity. Blood samples and broncho-alveolar lavages were collected every 3 d, and necropsies were performed upon euthanasia 9 or 15 d after infection. EGFP production by MV-infected cells was visualized macroscopically, in both living and sacrificed animals, and microscopically by confocal microscopy and FACS analysis. At the peak of viremia, EGFP fluorescence was detected in skin, respiratory and digestive tract, but most intensely in all lymphoid tissues. B- and T-lymphocytes expressing CD150 were the major target cells for MV infection. Highest percentages (up to 30%) of infected lymphocytes were detected in lymphoid tissues, and the virus preferentially targeted cells with a memory phenotype. Unexpectedly, circulating monocytes did not sustain productive MV infection. In peripheral tissues, large numbers of MV-infected CD11c+ MHC class-II+ myeloid dendritic cells were detected in conjunction with infected T-lymphocytes, suggesting transmission of MV between these cell types. Fluorescent imaging of MV infection in non-human primates demonstrated a crucial role for lymphocytes and dendritic cells in the pathogenesis of measles and measles-associated immunosuppression.
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spelling doaj-art-36055ec898274357aec538a1c469e3382025-08-20T03:22:26ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742007-11-01311e17810.1371/journal.ppat.0030178Predominant infection of CD150+ lymphocytes and dendritic cells during measles virus infection of macaques.Rik L de SwartMartin LudlowLot de WitteYusuke YanagiGeert van AmerongenStephen McQuaidSelma YükselTeunis B H GeijtenbeekW Paul DuprexAlbert D M E OsterhausMeasles virus (MV) is hypothesized to enter the host by infecting epithelial cells of the respiratory tract, followed by viremia mediated by infected monocytes. However, neither of these cell types express signaling lymphocyte activation molecule (CD150), which has been identified as the receptor for wild-type MV. We have infected rhesus and cynomolgus macaques with a recombinant MV strain expressing enhanced green fluorescent protein (EGFP); thus bringing together the optimal animal model for measles and a virus that can be detected with unprecedented sensitivity. Blood samples and broncho-alveolar lavages were collected every 3 d, and necropsies were performed upon euthanasia 9 or 15 d after infection. EGFP production by MV-infected cells was visualized macroscopically, in both living and sacrificed animals, and microscopically by confocal microscopy and FACS analysis. At the peak of viremia, EGFP fluorescence was detected in skin, respiratory and digestive tract, but most intensely in all lymphoid tissues. B- and T-lymphocytes expressing CD150 were the major target cells for MV infection. Highest percentages (up to 30%) of infected lymphocytes were detected in lymphoid tissues, and the virus preferentially targeted cells with a memory phenotype. Unexpectedly, circulating monocytes did not sustain productive MV infection. In peripheral tissues, large numbers of MV-infected CD11c+ MHC class-II+ myeloid dendritic cells were detected in conjunction with infected T-lymphocytes, suggesting transmission of MV between these cell types. Fluorescent imaging of MV infection in non-human primates demonstrated a crucial role for lymphocytes and dendritic cells in the pathogenesis of measles and measles-associated immunosuppression.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.0030178&type=printable
spellingShingle Rik L de Swart
Martin Ludlow
Lot de Witte
Yusuke Yanagi
Geert van Amerongen
Stephen McQuaid
Selma Yüksel
Teunis B H Geijtenbeek
W Paul Duprex
Albert D M E Osterhaus
Predominant infection of CD150+ lymphocytes and dendritic cells during measles virus infection of macaques.
PLoS Pathogens
title Predominant infection of CD150+ lymphocytes and dendritic cells during measles virus infection of macaques.
title_full Predominant infection of CD150+ lymphocytes and dendritic cells during measles virus infection of macaques.
title_fullStr Predominant infection of CD150+ lymphocytes and dendritic cells during measles virus infection of macaques.
title_full_unstemmed Predominant infection of CD150+ lymphocytes and dendritic cells during measles virus infection of macaques.
title_short Predominant infection of CD150+ lymphocytes and dendritic cells during measles virus infection of macaques.
title_sort predominant infection of cd150 lymphocytes and dendritic cells during measles virus infection of macaques
url https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.0030178&type=printable
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