4.7 Article

Middle East Respiratory Syndrome Coronavirus Efficiently Infects Human Primary T Lymphocytes and Activates the Extrinsic and Intrinsic Apoptosis Pathways

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 213, Issue 6, Pages 904-914

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiv380

Keywords

MERS-CoV; T lymphocytes; apoptosis; caspase; tonsil; spleen; marmosets

Funding

  1. Research Grants Council of the Hong Kong Special Administrative Region, China [T11/707/15]
  2. Providence Foundation Limited
  3. University of Hong Kong [201409176024]
  4. Hong Kong Health and Medical Research Fund [14131392]
  5. Hong Kong Research Grants Council [N_HKU728/14]
  6. National Science and Technology Major Projects of Infectious Disease [2012ZX10004501-004]

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Middle East respiratory syndrome (MERS) is associated with a mortality rate of >35%. We previously showed that MERS coronavirus (MERS-CoV) could infect human macrophages and dendritic cells and induce cytokine dysregulation. Here, we further investigated the interplay between human primary T cells and MERS-CoV in disease pathogenesis. Importantly, our results suggested that MERS-CoV efficiently infected T cells from the peripheral blood and from human lymphoid organs, including the spleen and the tonsil. We further demonstrated that MERS-CoV infection induced apoptosis in T cells, which involved the activation of both the extrinsic and intrinsic apoptosis pathways. Remarkably, immunostaining of spleen sections from MERS-CoV-infected common marmosets demonstrated the presence of viral nucleoprotein in their CD3(+) T cells. Overall, our results suggested that the unusual capacity of MERS-CoV to infect T cells and induce apoptosis might partly contribute to the high pathogenicity of the virus.

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