Spotlight on Horvat & Reynaud from INSERM

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Spotlight on Horvat & Reynaud from INSERM

Branka Horvat, MD, PhD, Director of Research at the International Centre for Infectiology Research in Lyon, France (INSERM), and her doctoral student Josephine Reynaud have recently published an important paper on a new transgenic mouse model for HHV-6A. The paper demonstrates how HHV-6A infection leads to viral persistence and induces neuroinflammation via TLR9. It is the third paper to be published by this group on HHV-6 in two years. The group has published two review papers in the past year as well, one on animals models for HHV-6, and the other on HHV-6 and neuroinflammation.

Originally from Yugoslavia, Branka spent three years at Yale and lectured in Croatia before arriving at INSERM, France in 1991. We asked Branka about her future plans for the mouse model. “We are interested to understand better the type of cells in the murine brain infected with HHV-6A, particularly those supporting long-term infection, and to characterize further cells infiltrating the brain after HHV-6A infection,” she explained, adding that grant proposals are in progress.

One of the interesting findings was that HHV-6A persisted in the mouse brains for 9 months. We asked if there were signs of persistent infection after nine months. “The longest period we looked at was 10 months after infection. In that very last experiment 7 out of 7 HHV-6A-infected CD46 transgenic mice were still positive for viral DNA” she explained. “It is highly possible that HHV-6A DNA could persist longer than 10 months” she added, but Josephine had to wrap up the project before leaving for her new position as a post-doctoral researcher at University of Alabama.

We also asked if there was any evidence of HHV-6 infection in neurons, as is the case with measles, another virus that uses CD46 as a receptor. “In most of the studies described so far it seems that in human brain HHV-6 infects preferentially microglial cells while measles virus infects preferentially neurons. However, additional work is required to elucidate these questions and to identify HHV-6 cell targets in the murine brain. It may be interesting to test co-infection with these two viruses, to analyze whether measles could ‘wake up’ persistent HHV-6A infection in murine brain, as some papers suggest to happen in humans. Our model opens new avenues for this type of in vivo approaches.”