Animal models for human herpesvirus 6 infection

Joséphine M Reynaud,Branka Horvat

doi:10.3389/fmicb.2013.00174

Abstract

Human herpesvirus (HHV)-6A and HHV-6B are two enveloped DNA viruses of β-herpesvirus family, infecting over 90% of the population and associated with several diseases, including exanthema subitum (for HHV-6B), multiple sclerosis and encephalitis, particularly in immunosuppressed patients. Animal models are highly important to better understand the pathogenesis of viral infections. Naturally developed neutralizing antibodies to HHV-6 or a related virus were found in different species of monkeys, suggesting their susceptibility to HHV-6 infection. Both HHV-6 DNA and infectious virus were detected in experimentally infected Cynomolgus and African green monkeys, although most animals remained clinically asymptomatic. Furthermore, HHV-6A infection was shown to accelerate the progression of AIDS (acquired immunodeficiency syndrome) in macaques and to lead to the development of neurological symptoms in the marmoset model. Humanized SCID (severe combined immunodeficiency) mice efficiently replicated HHV-6 and were also susceptible to coinfection with HHV-6 and HIV-1 (human immunodeficiency virus 1). As CD46 was identified as a receptor for HHV-6, transgenic mice expressing human CD46 may present a potentially interesting model for study certain aspects of HHV-6 infection and neuroinflammation.

Highlights

Human herpesvirus (HHV)-6 belongs to the β-Herpesviridae subfamily, together with its closest homolog HHV-7 and human cytomegalovirus (HCMV)
Numerous clinical studies have established a correlation between HHV-6A and -6B infection and the demyelinating, autoimmune disease-multiple sclerosis, and both viruses are thought to be involved in the development of certain cases of encephalitis, meningitis, and epilepsy (Theodore et al, 2008; Yao et al, 2010)
An active and wide-spread HHV-6 infection was observed in acquired immunodeficiency syndrome (AIDS) patients (Knox and Carrigan, 1994; Secchiero et al, 1995) and AIDS was described to progress rapidly after primary HHV-6 infection in children with vertically inherited human immunodeficiency virus (HIV; Kositanont et al, 1999)

Summary

INTRODUCTION

Human herpesvirus (HHV)-6 belongs to the β-Herpesviridae subfamily, together with its closest homolog HHV-7 and human cytomegalovirus (HCMV). An active and wide-spread HHV-6 infection was observed in AIDS patients (Knox and Carrigan, 1994; Secchiero et al, 1995) and AIDS was described to progress rapidly after primary HHV-6 infection in children with vertically inherited human immunodeficiency virus (HIV; Kositanont et al, 1999). A few antiviral drugs have been shown to be efficient against HHV-6 infection in vitro (Manichanh et al, 2000; De Clercq et al, 2001; De Bolle et al, 2005b) and were successfully used for the treatment of patients suffering from encephalitis following viral reactivation (reviewed in De Bolle et al, 2005b) These treatments are often associated with strong adverse effects and fully controlled specific clinical studies demonstrating their in vivo efficiency are still missing. The use of animal models has brought new evidence of the capacity of HHV-6A to induce neuropathology and has allowed the study of the interactions between HHV-6 and immunodeficiency viruses, showing a role of HHV-6A in AIDS progression and providing potential explanations for the impact of HHV-6A on the course of HIV infection

Virological data

SIMIAN MODELS

Findings

CONCLUSION