HHV-6 and the immune system: mechanisms of immunomodulation and viral escape.
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.
Lusso
Paolo
P
Unit of Human Virology, Department of Biological and Technical Research (DIBIT), San Rafaele Scientific Institute, Milano, Italy. paolo.lusso@hsr.it
D000163:Acquired Immunodeficiency Syndrome / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D003165:Complement System Proteins / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D018450:Disease Progression; D015497:HIV-1 / Q000472:pathogenicity; D015654:Herpesvirus 6, Human / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D016131:Lymphocyte Subsets / Q000821:virology*; D019349:Roseolovirus Infections / Q000276:immunology* / Q000821:virology*; D013601:T-Lymphocytes / Q000821:virology*
D016207:Cytokines; D003165:Complement System Proteins