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

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

研究成果: ジャーナルへの寄稿学術誌査読

206 被引用数 (Scopus)

抄録

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. Band 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 Tlymphocytes, suggesting transmission of MV between these cell types. Fluorescent imaging of MV infection in nonhuman primates demonstrated a crucial role for lymphocytes and dendritic cells in the pathogenesis of measles and measles-associated immunosuppression.

本文言語英語
ページ(範囲)1771-1781
ページ数11
ジャーナルPLoS pathogens
3
11
DOI
出版ステータス出版済み - 11月 2007

!!!All Science Journal Classification (ASJC) codes

  • 寄生虫科
  • 微生物学
  • 免疫学
  • 分子生物学
  • 遺伝学
  • ウイルス学

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