Investigators from University of Michigan have demonstrated that murine roseolovirus is a useful homolog for the study of HHV-6 reactivation in lung disease. In a large retrospective study of HCT patients, they also found early HHV-6 reactivation to increase the risk of both idiopathic pneumonia syndrome and non-relapse mortality.
MS patients with a particular haplotype on natural killer cells are more susceptible to HHV-6A infection. Similarly, HHV-6A/B may contribute to Alzheimer’s by utilizing a specific NK cell inhibitory receptor to disrupt the ability of NK cells to clear infected cells.
A 73% of 165 hematopoietic stem cell transplant patients tested for possible encephalitis were positive for HHV-6 in a recent review. Only 10% were positive for EBV and no other virus was positive in more than 3% of cases. The outcome for patients with viral infection was poor with 50% mortality within 6 months and only 30% survival at 5 years.
Investigators from the Children’s Hospital of Mexico found that although CMV caused the biggest increase in risk for liver rejection, HHV-6 was the more important infection associated with rejection of kidney transplants. A single HHV-6 infection resulted in an increased risk of over 5 fold, while a coinfection of EBV, HHV-6 and HHV-7 increased the risk of kidney rejection by over 17 fold.
Herpesviruses are common in the trigeminal and facial ganglia, latently infecting 64% of cases. HHV-6 was the most commonly identified herpesvirus in these tissues- about half of all autopsy specimens were found to have the virus in trigeminal and/or facial ganglia.
HHV-6 was found to be significantly correlated with nerve fiber damage severity by Latvian investigators. 51% of fibromyalgia patients had detectable HHV-6 DNA in whole blood compared to just 6% of controls.
Since its discovery, HHV-6 has been studied in the context of lymphoproliferative disorders and various types of cancer. Several obstacles, particularly the ubiquitous nature of the virus, have made it difficult to determine exactly how HHV-6 might, or might not, be involved in tumor development.
A team at Stanford reported that 48% of young children with “liver failure of unknown etiology” had high viral loads of HHV-6 in their liver tissues. As a result, Stanford has now instituted routine evaluation for HHV-6 in all children who present with liver failure.
Both infectious and UV-inactivated HHV-6A activate endogenous retrovirus envelope protein – but so does selective stimulation of HHV-6A’s CD46 receptor. This “cross-talk” between HHV-6A and endogenous retrovirus appears to play an important role in the pathogenesis of inflammatory diseases.
Porcine CMV is an immunosuppressive virus that inhibits T-lymphocyte and macrophage immune functions, and like HHV-6A, it causes infertility. Porcine CMV infection also reduces the survival of pig xenotransplants.
The HHV-6 latency gene U94 has been found to block angiogenesis, but the mechanisms behind this phenomenon have been unclear. A team lead by Roberta Rizzo and Elisabetta Caselli in Italy shed light on this process, opening the door to new potential molecular targets to pursue in treating diseases marked by improper vascularization.
A group led by Mara Cirone in Italy found that HHV-6B blocks autophagy in HSB-2 cells. Both HSV-1 and CMV have proteins that block autophagy, and HHV-6B carries genes that are homologues of those encoding for CMV’s anti-autophagy protein. Her next step is to study the impact of both HHV-6A and HHV-6B on autophagy in neuronal cells.
Investigators at University of Washington studied multiple samples to develop an assay that can detect active infection in patients with chromosomally integrated HHV-6. Current quantitative PCR DNA testing cannot determine whether a ciHHV6 patient has active replication.
Marmosets infected with HHV-6A/B intranasally were initially asymptomatic but later developed significantly accelerated disease and died in a shorter period of time. HHV-6 proteins were found at high levels in the brain lesions.
A genomic analysis of samples from 141,431 Chinese women found a highly significant association between ciHHV-6 and a variant in the MLCI-MOV10L region. The MLC1 gene is involved in myeloid cell differentiation and the MOV10L1 gene may allow for more efficient integration during spermatogenesis.