Phylogenetic studies of frequently diagnostically sampled herpesviruses - Possibilities for clinical applications?

With the modern sequencing technologies and the capability to sequence large viral genomes virtually overnight, full-genome sequencing of large DNA viruses and correlating any sequence variation to specific clinical manifestations is now eminently feasible - but is it worth doing, i.e. can such large-scale viral genomic analyses be clinically useful? A few clinical conditions, such as organ and bone marrow transplant recipients, require the regular diagnostic sampling and testing for certain viruses over an extended period of time. Such frequent sampling leads to the routine archiving of multiple samples from the same patient over an extended time period and it is the purpose of this mini-review to explore whether such routinely collected samples can be utilized for viral sequencing studies to produce clinically useful outcomes. Specific examples of this include the monitoring of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) levels in transplant recipients, as rising levels of these viruses in these patients can cause serious and sometimes fatal disease during the post-transplant period when their immune system is gradually recovering from the transplant process. Other herpesviruses, such as herpes simplex virus (HSV) and varicella zoster virus (VZV), may also reactivate and cause disease in post-transplant and other types of immunocompromised patients, though the specific complications may differ between patients. Although the natural mutation rate for these human herpes DNA viruses are very low, all of these viruses are capable of developing specific drug resistance within a few weeks of therapy, demonstrating that these viruses do have the ability to adapt rapidly to their local environment if the need arises. Specific problems with analyzing these large DNA virus genomes include the selection of the appropriate gene target (unless a full-genome analysis is the aim), and how to deal with overlapping and inverted reading frames, which are discussed in this mini-review.

► Important clinical aspects of individual DNA herpesviruses are summarized. ► Options for utilizing clinical samples for phylogenetic analysis are suggested. ► Practical problems, the feasibility and limitations of such approaches are discussed.