Although only a small number of pediatric cases have been reported in literature, the authors conclude that evidence suggests HHV-6 should be considered as a causative agent of inflammatory cardiomyopathy, particularly in young children (under 3 years of age) who might be experiencing a primary infection.
Investigators in Japan studied 145 patients who developed HHV-6 encephalitis. At 100 days after transplantation, the overall survival rate was just 58.3%, compared with 80.5% for patients who did not develop encephalitis. High-dose antiviral therapy was shown to mitigate high mortality rates in these patients.
Investigators at Kings College London report that seropositivity for CMV, Herpes simplex 1 and HHV-6 are all associated with a significant shortening of telomeres over a three-year period. Furthermore, the magnitude of the changes was large. For example, CMV seropositivity was associated with the equivalent of almost 12 years of chronological age.
Sequencing of over 8,000 individuals were used to determined the prevalence of 94 different viruses. HHV-7 was the most common virus, with HHV-6B and HHV-6A 4th and 5th respectively.
A group at University of Rochester demonstrated that the HHV-6A latency gene, U94, inhibits migration of cells involved in myelin repair. Inefficient myelin repair is associated with progression MS, and the ability of HHV-6A to impede this process suggests that it could be involved in the progression of MS, and raises questions about the virus’s role in other chronic demyelinating diseases.
T-cell depleted stem cell transplant patients at Memorial Sloan Kettering Cancer Center with HHV-6 viremia, CMV viremia, or 2 or more viremias experienced longer hospital stays and were readmitted more often. HHV-6 was the most commonly reactivated virus, with 61% of patients affected patients .
“Off-the-shelf” donor T cells primed to fight five specific viruses were shown to be effective in a Phase 2 trial backed by Viracyte. A single infusion produced a complete or partial response rate of 92%.
A team in Japan has reports that ciHHV-6A prevalence is influenced by a “founder effect” and is likely derived from a common ancestor. All of the individuals in the small study were found to have HHV-6A integrated into the telomeric region of chromosome 22, a common site of integration.
A higher prevalence of inherited virus was found in patients
Investigators at Fred Hutchinson Cancer Center determined that transplant patients with inherited ciHHV-6 were twice as likely to develop acute graft vs host disease and three times more likely to develop high level CMV viremia. Transplant patients were also significantly more likely to have inherited ciHHV-6 than donors.
CD8+ T cells recover but CD4+ T cells remain low
Investigators in France discovered that monocytes and B lymphocytes recover quickly and become abnormally elevated by day 75 in cord blood patients, while they remain below normal or normal in stem cell patients. Although CD8 T cells recover, CD4+ T cells remain below normal levels for six months in both groups.
Italian investigators found that HHV-6 latency-associated gene U94, inserted in a HSV1 vector, inhibited the development of breast cancer, cervical cancer, and lung metastasis. It also impaired tumor driven angiogenesis.
Retrospective analysis of transplant patients revealed that low serum sodium levels are associated with HHV-6 encephalitis, but not HHV-6 myelitis. Low sodium is a possible marker for HHV-6 encephalitis post-transplantation.
A group led by Louis Flamand, PhD in Canada has developed a culture system that can be used to determine how the virus enters latency by integrating into the chromosome, and which drugs cause it to activate.
Growing evidence implicates HHV-6, especially HHV-6A, in some cases of female infertility, miscarriage, and other gestational problems affecting both the mother and child. The authors of the paper wonder if heparin, an anticoagulant with antiviral properties often used to treat infertility, might mitigate the detrimental effects of HHV-6 in the uterine environment.
Over a dozen studies have now found HHV-6 to predict aGVHD, but this is the first to correlate viral reactivation with poor CD4+ cell immune reconstitution.