HHV-6 is a double stranded DNA virus belonging to the betaherpesvirinae subfamily. HHV-6 viruses comprise two distinct species: HHV-6A and HHV-6B. HHV-6 is a T-cell lymphotropic virus with high affinity for CD4 lymphocytes and is capable of infecting virtually all human beings. HHV-6B is responsible for at least 97% of HHV-6 infections in the USA while HHV-6A is frequently associated with patients with neuroinflammatory diseases such as multiple sclerosis. HHV-6A and HHV-6B proteins share more than 92% of their amino acids composition. However, the immediate-early protein locus A, has less than 70% of homology between the two species. At this locus, IE1 and IE2 proteins are encoded with IE2 being the most divergent between HHV-6A and HHV-6B. IE2 is expressed within few hours’ post-infection and is a potent transactivator of multiple cellular and viral promoters.