Novel Monkey Model to Enable Study of Dormant Herpes Infections

A team of molecular virologists has demonstrated the potential of the pigtailed macaque monkey model as a platform to study the implications of dormant herpes viruses on individuals with compromised immune systems.

Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses and are highly prevalent in the human population. Roseolovirus reactivation in an immunocompromised host can cause severe disease. While the pathogenic potential of HHV-7 is unclear, it can reactivate HHV-6 from latency and thus contributes to severe pathological conditions associated with HHV-6 such as such as encephalitis, bone marrow suppression, and pneumonitis. Because of the ubiquitous nature of roseoloviruses, their roles in such interactions and the resulting pathological consequences have been difficult to study. Furthermore, the lack of a relevant animal model for HHV-7 infection has hindered a better understanding of its contribution to roseolovirus-associated diseases.

During their search for a suitable herpes animal model, investigators at Seattle Children’s Research Institute (WA, USA) discovered that pigtailed macaques were naturally infected with viral homologs of HHV-6 and HHV-7, which they provisionally named MneHV6 and MneHV7, respectively. In this study, they confirmed that MneHV7 was genetically and biologically similar to its human counterpart, HHV-7.

The investigators reported in the August 2016 issue of the journal Virology that they had determined the complete unique MneHV7 genome sequence and provided a comprehensive annotation of all genes. They also characterized viral transcription profiles in salivary glands from naturally infected macaques. They showed that broad transcriptional activity across most of the viral genome was associated with high viral loads in infected parotid glands and that late viral protein expression was detected in salivary duct cells and peripheral nerve ganglia.

“It is common to find herpes virus in salivary glands of humans and animals,” said senior author Dr. Serge Barcy, a research assistant professor at Seattle Children’s Research Institute. “But we found herpes-7 in the nervous system of animal models, which was a surprise because that strain of herpes has not been detected in the nervous system before. We want to understand what it does in the nervous system, if the virus is also in the human nervous system and if it could be associated with nerve diseases. More and more evidence is building that herpes viruses may use the nervous system as a highway to spread and could be interfering with normal nerve function under certain circumstances. Our next step in the research is to investigate this possible link.”

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Seattle Children’s Research Institute