Immunomodulation and immunosuppression by human herpesvirus 6A and 6B
http://www.futuremedicine.com/doi/abs/10.2217/fvl.13.7
Lorenzo Dagna Joshua C Pritchett & Paolo Lusso
 
Lorenzo Dagna Joshua C Pritchett & Paolo Lusso
   
Vol. 8, No. 3, Pages 273-287
, DOI 10.2217/fvl.13.7
  
        (doi:10.2217/fvl.13.7) 
"Like
 other members of the Herpesviridae family, human herpesvirus (HHV)-6A 
and HHV-6B have developed a wide variety of strategies to modulate or 
suppress host immune responses and, thereby, facilitate their own spread
 and persistence in vivo. Long considered two variants of the 
same virus, HHV-6A and HHV-6B have recently been reclassified as 
distinct viral species, although the established nomenclature has been 
maintained. In this review, we summarize the distinctive profiles of 
interaction of these two viruses with the human immune system. Both 
HHV-6A and HHV-6B display a tropism for CD4+ T lymphocytes, 
but they can also infect, in a productive or nonproductive fashion, 
other cells of the immune system. However, there are important 
differences regarding the ability of each virus to infect cytotoxic 
effector cells, as HHV-6A has been shown to productively infect several 
of these cells, whereas HHV-6B infects them inefficiently at best. In 
addition to direct cytopathic effects, both HHV-6A and HHV-6B can 
interfere with immunologic functions to varying degrees via cytokine 
modulation, including blockade of IL-12 production by professional 
antigen-presenting cells, modulation of cell-surface molecules essential
 for T-cell activation, and expression of viral chemokines and chemokine
 receptors. Some of these effects are related to signaling through and 
downregulation of the viral receptor, CD46, a key molecule linking 
innate and adaptive immune responses. Increasing attention has recently 
been focused on the importance of viral interactions with dendritic 
cells, which may serve both as targets of virus-mediated 
immunosuppression and as vehicles for viral transfer to CD4+ T
 cells. Our deepening knowledge of the mechanisms developed by HHV-6A 
and HHV-6B to evade immunologic control may lead to new strategies for 
the prevention and treatment of the diseases associated with these 
viruses. Moreover, elucidation of these viral mechanisms may uncover new
 avenues to therapeutically manipulate or modulate the immune system in 
immunologically mediated human diseases."
 
 
 
 
 
 
 
 
 
 
