HHV-6 and the immune system: mechanisms of immunomodulation and viral escape

J Clin Virol. 2006 Dec;37 Suppl 1:S4-10. doi: 10.1016/S1386-6532(06)70004-X.


Clinical and experimental evidence indicates that human herpesvirus 6 (HHV-6) can interfere with the function of the host immune system through a variety of mechanisms. Both HHV-6A and B can infect, either productively or nonproductively, several types of immune cells. The primary target for HHV-6 replication, both in vitro and in vivo, is the CD4+ T lymphocyte, a pivotal cell in the generation of humoral and cell-mediated adaptive immune responses. HHV-6A, but not B, also replicates in various cytotoxic effector cells, such as CD8+ T cells, gammadelta T cells and natural killer cells. In professional antigen-presenting cells like macrophages and dendritic cells, HHV-6 infection is typically nonproductive; yet, it induces dramatic functional abnormalities, including a selective suppression of IL-12, a critical cytokine in the generation of Th1-polarized antiviral immune responses. This and other immunomodulatory effects seem to be mediated by the engagement of the primary HHV-6 receptor, CD46. Moreover, HHV-6 infection results in a generalized loss of CD46 expression in lymphoid tissue, which may lead to an aberrant activation of autologous complement. Additional mechanisms of immunomodulation by HHV-6 include alterations in cell surface receptor expression and cytokine/chemokine production. HHV-6 can also modulate influence responses through the expression of virally-encoded homologs of chemokines and chemokine receptors. By modulating specific antiviral immune responses, HHV-6 can facilitate its own spread and persistence in vivo, as well as enhance the pathogenic effects of other agents, such as human immunodeficiency virus.

Publication types

  • Review

MeSH terms

  • Acquired Immunodeficiency Syndrome / virology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • Complement System Proteins / immunology
  • Cytokines / biosynthesis*
  • Disease Progression
  • HIV-1 / pathogenicity
  • Herpesvirus 6, Human / immunology
  • Herpesvirus 6, Human / pathogenicity
  • Humans
  • Lymphocyte Subsets / virology*
  • Roseolovirus Infections / immunology*
  • Roseolovirus Infections / virology*
  • T-Lymphocytes / virology*


  • Cytokines
  • Complement System Proteins