Evasion of CD8+ T cells is critical for superinfection by cytomegalovirus

Science. 2010 Apr 2;328(5974):102-6. doi: 10.1126/science.1185350.


Cytomegalovirus (CMV) can superinfect persistently infected hosts despite CMV-specific humoral and cellular immunity; however, how it does so remains undefined. We have demonstrated that superinfection of rhesus CMV-infected rhesus macaques (RM) requires evasion of CD8+ T cell immunity by virally encoded inhibitors of major histocompatibility complex class I (MHC-I) antigen presentation, particularly the homologs of human CMV US2, 3, 6, and 11. In contrast, MHC-I interference was dispensable for primary infection of RM, or for the establishment of a persistent secondary infection in CMV-infected RM transiently depleted of CD8+ lymphocytes. These findings demonstrate that US2-11 glycoproteins promote evasion of CD8+ T cells in vivo, thus supporting viral replication and dissemination during superinfection, a process that complicates the development of preventive CMV vaccines but that can be exploited for CMV-based vector development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology
  • Cytomegalovirus / physiology*
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology*
  • Cytomegalovirus Vaccines / immunology
  • Disease Models, Animal
  • Gene Products, gag / immunology
  • Genes, Viral
  • Histocompatibility Antigens Class I / immunology
  • Immune Evasion*
  • Immunologic Factors / genetics
  • Immunologic Factors / physiology*
  • Macaca mulatta
  • Male
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology
  • Superinfection
  • Viral Proteins / genetics
  • Viral Proteins / physiology*
  • Virus Replication
  • Virus Shedding


  • Cytomegalovirus Vaccines
  • Gene Products, gag
  • Histocompatibility Antigens Class I
  • Immunologic Factors
  • Viral Proteins

Associated data

  • GEO/GSE20308