CiHHV-6A is the dominant virus in malignancy and inflammatory disease cases, while ciHHV-6B is the dominant virus in myocarditis cases

In All, ciHHV-6, Heart Disease, News by hhv6foundation

Divergent disease associations suggested for ciHHV6-A and ciHHV-6B

Although HHV-6B accounts for >97% of reactivation cases in transplant patients, a new study indicates that ciHHV-6A is likely the dominant virus in patients with malignancy. 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 ciHHV-6A 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.

The integrated genomes encoded the “secreted active form” of virus chemokines. Other findings that support the argument that integrated virus can reactivate include: 1) ciHHV-6A recombined with HHV-B in 20% of the malignancy/inflammatory disease cases, 2) a subset of integrated samples expressed early/late transcripts from chemokine receptor inflammatory mediator genes, and 3) deep sequencing revealed that superinfection resulted in minor variations only in ciHHV-6A individuals that were actively expressing transcripts.

Gompels calls ciHHV-6A an emergent virus with potent encoded chemokine and chemokine receptors. She notes that the active alleles present in the ciHHV-6 genomes, and evidence for gene expression in a subset of patients, indicate that these are novel human genes, which may underlie diverse inflammatory conditions. She adds that the ability to reactivate via superinfection combined with demonstrated chemokine leukocyte chemoattractant properties make it clear that ciHHV-6A is an important emergent infection.

HHV-6A has been infection linked with glial malignancy (Chi 2012) and thyroid disease (Caselli 2012) as well as neuroinflammatory diseases that involve glial cells and demyelination such as multiple sclerosis (Liebovitch 2014).

Gompels explains that the association of ciHHV-6B in German patients with cardiovascular disease is consistent with expression of the active ‘long’ form of HHV-6B U83 chemokine, which mimics human CCL2 (MCP-1) which is associated with cardiovascular disease.Parvovirus B19 and HHV-6 are the two most common viruses found in endomyocardial biopsies of patients with left ventricular dysfunction and myocarditis (Kühl 2005, Kühl 2005b).

Collaborators on this paper include Petr Hubacek from Czech republic who studied ciHHV-6 in patients with malignancies (Hubacek 2013) as well as cardiology specialists Uwe Kühl and Dirk Lassner from Berlin who have studied HHV-6 and ciHHV-6 in patients with heart failure (Kühl 2014).

For more information, read the full paper.