Novel Marmoset (Callithrix jacchus) Model of Human Herpesvirus 6A and 6B Infections: Immunologic, Virologic and Radiologic Characterization

PLoS Pathogens

Daniel S. Reich¹  Jillian E. Wohler²  Afonso Silva³  Kelsey Motanic³  Susan Westmoreland³  Steven Jacobson⁴  Pietro Maggi⁴  Mary Ellis⁴  Sheila M. Cummings Macri⁵  María I. Gaitán⁵  Emily Leibovitch⁵  Erin Harberts⁵ 

[1] Cerebral Microcirculation Unit, Laboratory of Functional and Molecular Imaging, NINDS/NIH, Bethesda, Maryland, United States of America;Institute for Biomedical Sciences, George Washington University, Washington, DC, United States of America;New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, United States of America;Translational Neuroradiology Unit, Neuroimmunology Branch, NINDS/NIH, Bethesda, Maryland, United States of America;Viral Immunology Section, Neuroimmunology Branch, NINDS/NIH, Bethesda, Maryland, United States of America

关键词: Marmosets;    Central nervous system;    Magnetic resonance imaging;    Spinal cord;    Multiple sclerosis;    Antibody response;    Antibodies;    Saliva;   

DOI  :  10.1371/journal.ppat.1003138

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Human Herpesvirus 6 (HHV-6) is a ubiquitous virus with an estimated seroprevalence of 95% in the adult population. HHV-6 is associated with several neurologic disorders, including multiple sclerosis, an inflammatory demyelinating disease affecting the CNS. Animal models of HHV-6 infection would help clarify its role in human disease but have been slow to develop because rodents lack CD46, the receptor for cellular entry. Therefore, we investigated the effects of HHV-6 infections in a non-human primate, the common marmoset Callithrix jacchus. We inoculated a total of 12 marmosets with HHV-6A and HHV-6B intravenously and HHV-6A intranasally. Animals were monitored for 25 weeks post-inoculation clinically, immunologically and by MRI. Marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms and generated virus-specific antibody responses, while those inoculated intravenously with HHV-6B were asymptomatic and generated comparatively lower antibody responses. Viral DNA was detected at a low frequency in paraffin-embedded CNS tissue of a subset of marmosets inoculated with HHV-6A and HHV-6B intravenously. When different routes of HHV-6A inoculation were compared, intravenous inoculation 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. Moreover, marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms, while marmosets inoculated with HHV-6A intranasally were asymptomatic. We demonstrate that a marmoset model of HHV-6 infection can serve to further define the contribution of this ubiquitous virus to human neurologic disorders.

【 授权许可】

CC BY