A new study shows that HHV-6A direct repeats can survive alone in an integrated state without the rest of the viral genome. The study also identified non-telomeric integration of HHV-6A in both in vitro cultured cells as well as one iciHHV-6A patient.
Human papillomavirus 4 is a benign strain not associated with cancer. However, in a woman with inherited chromosomally integrated HHV-6A, a high grade vaginal squamous lesion developed rapidly. The authors warn that there may be a synergistic effect between HPV4 and iciHHV6A.
Two physicians from Texas propose that ciHHV6 status of donors and recipients be determined before solid organ transplantion, using a single pre-transplant qPCR test on whole blood, and that patients with ciHHV-6 or ciHHV-6 donors be carefully monitored for signs of active HHV-6 infection.
Investigators from the University of Ferrara, Italy have found evidence suggesting that high levels of U94 in ciHHV6 may predispose to the formation of marker chromosomes. A patient with diffuse large B-cell lymphoma positive for inherited chromosomally integrated HHV-6A and HHV-6A was also found in a marker chromosome, an abnormal piece of chromosome that is seen in some leukemia and lymphomas.
Investigators led by Bhupesh Prusty, PhD at University of Wurzbürg in Germany have identified two cases of possible germline inherited chromosomally integrated HHV-7.
A pregnant ciHHV-6B woman with a history of miscarriages was given weekly doses of high dose progesterone. Could progesterone, like hydrocortisone, activate integrated ciHHV-6 in vitro.
When the research team led by Benedikt Kaufer attempted to shed light on the mechanism behind HHV-6 integration, they were suprised to find telomeric repeats were critical to the integration process. Since the U94 gene shares homology and biological properties with the adenovirus Rep68 gene responsible for viral integration into human chromosomes, U94 was considered the most likely candidate to mediate HHV-6 integration.
A group led by Ursula Gompels from the London School of Hygiene & Tropical Medicine, University of London, did next generation sequencing on three ciHHV6A cardiac patients and found superinfections of HHV-6A in two of the three. They characterized the first full genome sequence of ciHHV-6A and demonstrated the inherited ciHHV6 genome was similar but distinct from known exogenous (community acquired) strains of HHV-6A .
In an article published this month in the Proceedings of the National Academy of Sciences, Dr. Louis Flamand’s team has described a relationship between inherited chromosomally integrated HHV-6 (iciHHV-6) and the development of angina pectoris.
Since the discovery of chromosomally integrated HHV-6 (ciHHV-6), investigators have wondered about the potential consequences of having chromosome integrated HHV-6 in the genome.
A sequencing study led by Ursula Gompels of London School of Hygiene & Tropical Medicine, found that 95% (19/21) of Czech ciHHV-6 malignancy and inflammatory disease patients had ciHHV6A while 65% (13/20) of a German myocarditis cohort had ciHHV-6B. The authors propose that this divergence suggests different disease links for the two viruses.
ciHHV-6 infants score 4 points lower than controls on the Bayley Mental Development Index
Scottish study finds inheritance of ciHHV-6 does not increase the risk of developing cHL
Dr. Flamand, a professor and molecular virologist at Université Laval in Quebec city, has written an editorial calling for screening of organ donors for ciHHV-6 status and careful monitoring of recipients of ciHHV-6 donor tissues for signs of active HHV-6 infection and HHV-6 antigen-induced immune rejection. Flamand also questions whether solid organs and stem cells derived from persons with ciHHV-6 should be used in transplantation.
Experts emphasize need for larger studies to determine the impact of ciHHV-6 on patient outcomes
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