ABSTRACT
Shortly after the discovery of human herpesvirus 6 (HHV-6), two distinct variants, HHV-6A and HHV-6B, were identified. In 2012, the International Committee on Taxonomy of Viruses (ICTV) classified HHV-6A and HHV-6B as separate viruses. This review outlines several of the documented epidemiological, biological, and immunological distinctions between HHV-6A and HHV-6B, which support the ICTV classification. The utilization of virus-specific clinical and laboratory assays for distinguishing HHV-6A and HHV-6B is now required for further classification. For clarity in biological and clinical distinctions between HHV-6A and HHV-6B, scientists and physicians are herein urged, where possible, to differentiate carefully between HHV-6A and HHV-6B in all future publications.
Subject(s)
Genetic Variation , Herpesvirus 6, Human/classification , Herpesvirus 6, Human/genetics , Roseolovirus Infections/virology , Humans , Roseolovirus Infections/epidemiology , Roseolovirus Infections/immunologyABSTRACT
The human herpesvirus 6 (HHV-6) variant A genome has conserved sequences which are signals for initiating lytic replication (origin, 'ori-lyt') and DNA packaging into the virion (pac2/1). Here these are functionally characterised and used to construct a gene-expression amplifiable-vector, an 'amplicon', with applications for gene delivery to lymphoid-myeloid cells or their progenitor stem cells. A minimal efficient ori-lyt for replication was identified which was enhanced in the presence of the imperfect direct repeated DNA domain (IDR). In A variant strains these are arranged as three adjacent repeats with the most divergence in IDR3. Addition of the pac2/1 sequences also enhanced detection of ori-lyt replication and conferred DNA packaging properties, thus, the amplicon could be packaged with 'helper' virus. An HHV-6 specific factor, which inhibits amplicon replication was identified by trans replication assays. This is the U94-Rep 'latency' gene product, which can modulate efficiency of such amplifiable vectors, based on the lytic origin. It could also affect maintenance of viral genomes or vectors during latency.
