The reactivation of HHV-6 in transplant recipients has long been known to induce clinical complications and poor outcomes following transplantation.  However, the clinical relevance of transplant patients with Chromosomally-integrated HHV-6 (CIHHV-6)—an inheritable and transmissible condition in which the HHV-6 virus is integrated into the chromosomes of every host cell—has not yet been established.

A new study  from the Mayo Clinic, lead by Infectious Disease and Transplant specialist Dr. Raymund Razonable, looked at 548 cases of liver transplantation in an attempt to determine the clinical significance of CIHHV-6 among transplant patients.  While 1.3% of transplant patients were found to have CIHHV-6—a number consistent with the established prevalence of CIHHV-6 in the general population—the group found a higher rate of bacterial infection and allograft rejection in CIHHV-6 patients as compared to transplant recipients without the condition.   Their data suggest that patients with CIHHV-6 may be at an increased risk of complications following transplantation.

http://www.ncbi.nlm.nih.gov/pubmed/21629177

Click here to learn more about HHV-6 and Transplantation.

Since its initial description, Hodgkin’s Lymphoma (HL) has been considered as an infectious disease.  Initially, Epstein Bar Virus (EBV) was identified in 25%-40% of HL. For the first time, another virus other than EBV has been implicated in HL.

By examining 48 lymph node biopsies previously found positive for HHV-6B DNA, Lacroix et al demonstrated the presence of HHV-6B in the Reed Sternberg (RS) cells of 39.5% of the nodular sclerosis subset of HL, and even more surprising, they found that the HHV-6B specific protein DR7B was detected in 73.7% of these tissues.  Interestingly, this subset of HL tissue was EBV-negative.  By showing that HHV-6B transactivates NFkB and increases Id2 expression through the expression of DR7B, HHV-6 has now been implicated as an oncogenic agent in the nodular sclerosis subset of Hodgkin’s Lymphoma.  Also, detection of DR7B in the RS cells of EBV-negative HL patients may be considered as a surrogate marker for the identification of patients with a high probability of remission. (Lacroix 2010).

HHV-6 integrates into the chromosome during latency and reactivates in response to chemical stimulation. Peter Medveczky and colleagues determined that HHV-6 uses a novel form of latency. The virus finds safe harbor inside the human chromosomes to evade the immune system. Medveczky made this surprising finding by studying patients who have a rare form of HHV-6. These patients are actually born with HHV-6 integrated into every cell of their body, and the virus is passed from parent to child. Many scientists believed that this integrated virus could not be reactivated, but Medveczky’s group determined that chemical stimulation can cause the integrated virus to reactivate and start producing active virus. See Abstract from PNAS.

Dr. Yoshizo Asano was presented the “Dharam Ablashi Lifetime Achievement Award” at the 7th international conference on HHV-6 & 7. From left to right: Tetsushi Yoshikawa, Koichi Yamanishi, Dharam Ablashi, Yoshizo Asano, Kristin Loomis, Louis Flamand

The Chairs of the 2011 International Conference on HHV-6 & 7, Louis Flamand and Tetsushi Yoshikawa, were delighted to award Dr. Yoshizo Asano the Foundation’s Lifetime Achievement award. The author of over 90 publications on HHV-6 & 7, Yoshizo Asano served as Chair of the Pediatrics Department at Fujita Health University from 1994 to 2010 until retiring last year to become a professor for the Zambia Project at the Research Center for Zoonosis Control at Hokkaido University.

Dr. Asano has written over 90 papers on HHV-6 & HHV-7, often working with his close associate Tetsushi Yoskhikawa who succeeded him at Fujita Health University.
Before heading the Pediatrics Department, Dr. Asano was a visiting scientist at the FDA in Bethesda, Maryland and served in the pediatrics or virology departments at Nagoya University, Osaka University and Fujita Heath University.

The “Dharam Ablashi Lifetime Achievement Award” was established in 2006 and given every other year to an investigator who has contributed both extraordinary work and exemplary leadership in the field of HHV-6 research.

HHV-6 & MTLE in China

Mesial temporal lobe epilepsy brain tissue found to have HHV-6B DNA and elevated NF-κB expression. Dr. Li and colleagues from China have found that 28% of refractory epilepsy patients have high levels of HHV-6B DNA in their brain tissues when they have brain resections as a last resort to halt seizures. This study confirmed several earlier findings, including a 2007 study by NINDS investigators (Fotheringham 2007a). The Chinese group used immunohistochemistry, real time PCR and other techniques to demonstrate that the HHV-6 was found in the same cell locations as NF-κB, a key transcription factor associated with inflammatory responses. The subset of patients found with HHV-6-positive DNA had a history of febrile convulsions. Read Abstract.

HHV-6 & MTLE in Germany

HHV-6 DNA found in majority of epilepsy patients with a history of encephalitis. Niehusmann and colleagues from Germany found HHV-6 DNA in over 55% of the temporal lobe epilepsy patients with a history of encephalitis, and none of the controls, using nested PCR. Unlike the Li and Fotheringham studies featured above, they did not find HHV-6B in the subset of patients with a history of febrile seizures. The difference may be due in part to the fact that the Li and Fotheringham studies analyzed fresh rather than stored tissues. Read Abstract

HHV-6 in Febrile Status Epilepticus in USA

The FEBSTAT Study

Drs. Shinnar and Epstein at Northwestern University conducted a prospective study of the consequences of prolonged febrile seizures (FEBSTAT), which determined the frequency of HHV-6 and HHV-7 infection as a cause of febrile status eptilepticus (FSE).  Of the 119 children (ages 1 month to 5 years old) enrolled after presenting with FSE, HHV-6B viremia was found in 31% and HHV-7 viremia was found in 7% of patients at baseline.  Together, they account for one third of FSE, a condition associated with an increased risk of both hippocampal injury and subsequent temporal lobe epilepsy.  The FEBSTAT study is ongoing and the investigators have not yet published this data.