Dr. Steven Jacobson’s laboratory at the US National Institute of Health has developed a novel marmoset model for the study of HHV-6 infection. Because rodents lack CD46, the primary receptor for HHV-6 cellular entry, the field of HHV-6 research has been slow to develop animal models to study the role of HHV-6 in disease. However, the common marmoset is uniquely suited for the study of HHV-6 because of its genetic/immunological similarity to humans as well as its heightened susceptibility to infection. Jacobson’s group inoculated several of these animals (Callithrix jacchus) with HHV-6A and HHV-6B both intranasally and intravenously, then monitored them clinically, immunologically, and radiologically (via MRI) for 25 weeks post-inoculation.
The group identified several important distinctions between both viral species and route of viral transmission. Marmosets inoculated intravenously with HHV-6A and HHV-6B showed low-level DNA detection in CNS tissues, while only those inoculated intravenously with HHV-6A exhibited neurologic symptoms (including sensory and motor impairment, facial palsy, and diminished sensation in extremities) and robust anti-HHV-6 antibody responses. Furthermore, intravenous inoculation with HHV-6A resulted in virus-specific antibody responses and infrequent detection of viral DNA in the periphery, while intranasal inoculation resulted in negligible virus-specific antibody responses and frequent detection of viral DNA in the periphery. By contrast, marmosets inoculated intravenously with HHV-6B were asymptomatic and generated comparatively weaker antibody responses.
This marmoset model of HHV-6A and HHV-6B infection will allow researchers to further characterize the acquisition and host response to HHV-6A, which has been significantly correlated with several neurological manifestations but has yet to be fully elucidated in humans. Moreover, this model of infection will enable researchers to study how these viruses may trigger or contribute to disease, and thus can be utilized for preclinical testing of potential interventional strategies specific to HHV-6A and HHV-6B.
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