REVIEW: Important differences between the HHV-6A and HHV-6B viruses

Important differences between the HHV-6A and HHV-6B viruses: review

An international group of HHV-6 researchers worked together to compile a very useful review of the documented epidemiological, biological, and immunological distinctions between HHV-6A and HHV- 6B. Moving forward, the group urges scientists and physicians, where possible, to differentiate carefully between HHV-6A and HHV-6B in all future publications.

The article cites several existing complications that must be overcome while moving forward with differentiation assays, including the fact that since HHV-6A can be present at lower copy numbers than HHV-6B, assays that rely strictly on melting point analysis for differentiation may be biased toward the detection of HHV-6B, resulting in further confusion.  Furthermore, new serological assays are needed to allow researchers and clinicians alike to differentiate HHV-6A and HHV-6B in serological samples.

The two genomes share an overall common identity of 90% but show divergence of more than 30% in the immediate early (IE) region.

The authors are hopeful that strict adherence to the identification and differentiation of HHV-6B from HHV-6A virus will ultimately equip future physicians with a greater understanding of how to more effectively and comprehensively manage these infections in future clinical settings.

Among the most important differences:

  • HHV-6B is the dominant virus in peripheral blood cells and is the dominant virus that activates in transplant cases.
  • HHV-6B but not HHV-6A has been associated with febrile status epilepticus and mesial temporal lobe epilepsy.
  • HHV-6A but not HHV-6B has been implicated in Hashimoto’s thyroiditis and in syncytial-giant cell hepatitis.
  • HHV-6A has been identified in 72% of pediatric glial tumors and is the dominant virus found in MS.
  • HHV-6A, but not HHV-6B, has been shown to productively infect CD8+ T cells, natural killer cells and gamma/delta T cells
  • Both viruses utilize CD46 as a cellular receptor, HHV-6B utilizes CD134
  • HHV-6A but not HHV-6B can replicate in human neural stem cells and oligodendrocyte progenitor cells
  • HHV-6A can replicate in astrocytes; HHV-6B infection leads to abortive infection
  • HHV-6B chemokine u83B is specific for CCR2 and can attract cells during latent or lytic infection, while HHV-6A chemokine U83A has broader specificity affecting dendritic, NK activated and skin homing T cells
  • Several monoclonal antibodies are virus-specific
  • HHV-6B is the dominant virus in primary infection

For more information, read the full paper.