Association between chronic lung allograft dysfunction and human Cytomegalovirus UL40 peptide variants in lung-transplant recipients

J Heart Lung Transplant. 2021 Sep;40(9):900-904. doi: 10.1016/j.healun.2021.05.011. Epub 2021 May 31.

Abstract

Natural-Killer cells play an important role in the pathogenesis of chronic lung allograft dysfunction (CLAD) in lung-transplant recipients. Activating NKG2C+ and inhibitory NKG2A+ NK cells proliferate in response to human Cytomegalovirus (HCMV) infection via the presentation of virally encoded UL40 peptides on HLA-E molecules. We aimed to clarify whether infection with HCMV strains carrying different UL40 peptide variants is associated with the development of CLAD. We included 82 lung-transplant recipients, 18 patients developing CLAD and 64 matched control patients without CLAD. In all patients 1 episode of high-level HCMV-replication occurred. HCMV UL40 variants and Natural-Killer-cell proliferation with distinct UL40 peptides were assessed. The VMTPRTLIL variant was significantly overrepresented in patients developing CLAD (p < 0.0001) and lead to a significantly lower proliferation of inhibitory NKG2A+ cells, compared to the VMAPRTLIL, VMAPRTLVL and VMAPRTLLL variants (p < 0.0001). Thus, HCMV UL40 variants may contribute to development of CLAD over the NK cell response.

Keywords: CLAD; NK cells; NKG2C; UL40; human cytomegalovirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Allografts
  • Case-Control Studies
  • Chronic Disease
  • Cytomegalovirus / metabolism*
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / metabolism
  • Cytomegalovirus Infections / virology*
  • Female
  • Humans
  • Killer Cells, Natural / immunology*
  • Lung Transplantation*
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Primary Graft Dysfunction / immunology
  • Primary Graft Dysfunction / metabolism
  • Primary Graft Dysfunction / virology*
  • Retrospective Studies
  • Transplant Recipients*
  • Viral Proteins / metabolism*
  • Young Adult

Substances

  • UL40 glycoprotein, Cytomegalovirus
  • Viral Proteins