Roseoloviruses: Ubiquitous in humans and macaques
Human herpesviruses HHV-6A, 6B and 7 are classified as Roseoloviruses within the Betaherpesvirinae subfamily and are highly prevalent in the human population. Following primary infections roseoloviruses establish life-long latency with occasional reactivation. Viral reactivation in immuno-compromised patients can cause severe pathological conditions. Macaques are a valuable animal model of many different human viral diseases and represent an essential resource for biomedical research. Our project started with a question: is there a macaque viral homolog of HHV-6 and does it cause disease in macaques similar to that seen with HHV-6? Answering this simple question is important since multiple infectious agents present in a host have the potential to interact with each other and with their hosts, which often results in unexpected consequences. Indeed, the unsuspected presence of additional endogenous viruses may act as a confounding factor in many viral diseases. The serological data available in the literature suggested the existence of a roseolovirus in non-human primates; however, previous attempts to detect such a virus by PCR have failed.
We chose macaque saliva as DNA source hoping that a macaque HHV-6 homolog would be present in saliva as frequently as is HHV-6. Initially, we screened saliva from five macaques using CODEHOP PCR primers targeting a sequence conserved among roseolovirus DNA polymerase genes. In one macaque sample, we detected a fragment with a novel viral sequence closely related to the HHV-6 DNA polymerase. We named this virus MneHV6.
This was a serendipitous discovery since we later found that MneHV6 was not persistently secreted in macaque saliva. Our search could have ended there, but in an effort to enhance detection of MneHV6, we reanalyzed the same five saliva samples using a lower annealing temperature. To our surprise, this approach led to the amplification of a second distinct roselovirus DNA polymerase gene, this time closely related to HHV-7, which we called MneHV7. These findings have opened up the daunting but exciting task of further characterizing these two newly discovered viruses.
We have characterized the prevalence, oral shedding pattern, and tissue tropism for these novel macaque roseoloviruses by qPCR and more recently, we visualized viral protein expression by immuno-histochemistry (see picture). Our findings have shown strong similarities with the biological properties of the human roseoloviruses. Thus, macaque endogenous infection with MneHV6 and MneHV7 is a promising new animal model to study viral interactions between these roseoloviruses and to elucidate the mechanisms underlying roseolovirus associations with diseases.
Introducing Author Serge Barcy
About the research
Discovery and biological characterization of two novel pig-tailed macaque homologs of HHV-6 and HHV-7.
Virology, Volumes 471–473, December 2014, Pages 126–140
Jeannette P. Staheli, Michael R. Dyen, Patrick Lewis, Serge Barcy