HHV-6A and HHV-6B now recognized as two distinct viruses

Philip Pellett, Former Chair, Herpesvirales Working Group

The International Committee on Taxonomoy of Viruses (ICTV) has made it official. HHV-6A and HHV-6B are now considered distinct viruses as subspecies of roseoloviruses. The outcome of the vote has been published as a supplement to the Ninth report of the ICTV book of viruses and the master list can be downloaded from the ICTV web site.

The decision came two years after the Herpesvirales Working Group Chair, Philip Pellett, PhD received a petition from Dario Di Luca, Dharam Ablashi and a group of 18 leaders in the field of HHV-6 research asking the group to officially recognize the two “variants” as separate species.

HHV-6B causes 97 – 100% of primary HHV-6 infections in the USA and Japan and is responsible for a comparable percentage of transplant reactivation cases. HHV-6B, but not HHV-6A has been associated with febrile seizures, mesial temporal lobe epilepsy and status epilepticus.

HHV-6A has been found more frequently in patients with neuroinflammatory diseases such as multiple sclerosis (MS) arhomboencephalitis. HHV-6A is acquired later in life, usually without clinical symptoms, except in Sub-Saharan Africa where (unlike in the US and Europe) HHV-6A is the first of the two HHV-6 viruses to be acquired in the majority of the pediatric population.

HHV-6B is more prevalent than HHV-6A in the peripheral blood mononuclear cells of healthy adults and transplant patients, while HHV-6A is found more frequently in the plasma of HSCT patients. HHV-6B but not HHV-6A is commonly found in saliva. HHV-6A, but not HHV-6B can productively infect CD8+ T-cells, natural killer cells, and γ/δ (gamma/delta) T-cells.

HHV6-A will generally not infect cell lines readily infected by HHV-6 B and vice versa. There are also several monoclonal antibodies that will only interact with one or the other.

All HHV-6 isolates including those found in chromosomally integrated HHV-6 can be clearly designated either A or B. The IE1 gene shows 30% divergence between the two new species, but is very stable (>95%) within the clinical and laboratory isolates of each species.

Many HHV-6 publications do not specify which virus was used in the research. The authors of the petition on HHV-6A and HHV-6B, listed below, urge all investigators of HHV-6 to specify whether their research relates to HHV-6A or HHV-6B. Anyone interested in learning more details about the arguments to identify the two “variants” as two separate species, should contact the Committee Co-Chairs, Dario Di Luca or Dharam Ablashi.

Ad Hoc Committee on HHV-6A & HHV-6B Genomic Divergence
Dharam Ablashi, DVM, HHV-6 Foundation, Santa Barbara, USA (Co-chair)
Henri Agut, MD, PhD, Hospital Pitie-Salpetriere, Paris, France
Yoshizo Asano, MD, PhD, Fujita Health University, Toyoake, Aichi, Japan
Roberto Alvarez-LaFuente, MD, Hospital Clinico San Carlos, Madrid, Spain
Don Carrigan, PhD, Wisconsin Viral Research Group, Milwaukee, USA
Duncan Clark, PhD, Royal Free & University College Medical School, London, UK
Dario Di Luca, PhD, University of Ferrara, Ferrara, Italy (Co-Chair)
Steve Dewhurst, PhD, University of Rochester, USA
Louis Flamand, PhD, University Laval, Quebec, Canada
Niza Frenkel, PhD, Tel Aviv University, Tel Aviv, Israel
Robert Gallo, MD, Institute of Virology, University of Maryland, USA
Ursula Gompels, PhD, London School of Tropical Medicine, London, UK
Caroline Hall, MD, University of Rochester, Rochester, USA
Steve Jacobson, PhD, National Institute of Neurological Disorders & Stroke/NIH, Bethesda, USA
Kazuhiro Kondo, MD, PhD, Jikei University School of Medicine, Tokyo, Japan
Mario Luppi, MD, PhD, University of Modena and Reggio Emilia, Modena, Italy
Paolo Lusso, MD, PhD, National Institute of Allergy and Infectious Diseases/NIH, Bethesda, USA
Yasauki Mori, MD, PhD, National Institute of Biomedical Innovation, Osaka, Japan
Koichi Yamanishi, MD, PhD, National Institute of Biomedical Innovation, Osaka, Japan
Tetsushi Yoshikawa, MD, Nagoya University School of Medicine, Toyoake Aichi, Japan