**Subacute Sclerosing Panencephalitis and Other Lethal Encephalitis Caused by Measles Virus Infection: Pathogenesis and New Approaches to Treatment**

Fernandez-Muñoz R.\*, Carabaña J.1, Caballero M.1, Ortego J.2, Liton P.B.1, Duque B.M, Martin-Cortes A.3, Serrano-Pardo A., Muñoz-Alia M.A., Porras-Mansilla R., Alvarez-Cermeño J.C.4 and Celma M.L.\*

### **1. Introduction**

156 Non-Flavivirus Encephalitis

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Measles virus (MV) is a human, negative-stranded RNA virus, member of the Paramyxoviridae family, genus Morbillivirus. The virus enters cells by interaction of viral glycoprotein Hemagglutinin (H) with cellular receptors (CD46, CD150, CD147/EMMPRIN) and membrane fusion is mediated by viral fusion glycoprotein (F); helical nucleocapsids replicate in the cytoplasm on replication-transcription complexes formed by the viral catalytic subunit (L), the phosphoproteín (P) and the RNA wrapped in the viral nucleoprotein (N); virus particles bud out from plasmatic cell membrane patches internally lined by viral matrix protein(M). MV causes cytopathic effects by cell fusion forming syncytia, by inducing apoptosis, or both together, and may produce persistent infections in cultured cells and in the infected host. MV is highly lymphotropic infecting macrophages, lymphocytes and dendritic cells; causes systemic acute infections after cell-associated viremia generating life-long immunity (Griffin, 2007 for a review).

Despite the availability of an efficient live attenuated vaccine, MV still remains an important global pathogen infecting over 25 millions individuals and causing over 250.000 deaths per year, being one of the main causes of child death worldwide. Plans for the global eradication of measles are hindered by a number of factors: 1. high contagiousness of MeV (it is the most transmissible respiratory virus known, and it is needed a 95% to 98% protection in a population to avoid measles out-brakes), 2. vaccination fails in over 5% of the general population (non-responders), 3. vaccination has a low efficiency in infants under 9 months, 4. poor health care in some countries, and 5. objection to vaccination in sectors of the population.

*Virology Unit ( Madrid and Nacional Reference Laboratory for Measles Virus) Ramón y Cajal University Hospital, Madrid, Spain* 

*<sup>1</sup> Present address: Duke University Medical Center, Durham, NC, USA* 

*<sup>2</sup> Present address: Animal Health Research Center (CISA-INIA),Valdeolmos, Madrid, Spain* 

*<sup>3</sup> Present address: Complutense University of Madrid. Madrid, Spain* 

*<sup>4</sup> Neurology Department, Ramón y Cajal University Hospital, Madrid, Spain* 

*<sup>\*</sup> Corresponding authors* 

Subacute Sclerosing Panencephalitis and Other Lethal Encephalitis

Caused by Measles Virus Infection: Pathogenesis and New Approaches to Treatment 159

During acute measles, MV produces a transient clinical significant immunosuppression that can contribute to some complications as measles interstitial pneumonitis and giant cell pneumonia, otitis media and diarrhoea. Unfrequently, MV may cause Central Nervous System lethal complications as Acute measles post-infection disseminated encephalomyelitis (ADEM), Measles inclusion body encephalitis (MIBE), and Subacute sclerosing panencephalitis (SSPE) Figure 1 and Table1. In this chapter we will briefly review the epidemiology, clinical course, pathogenesis, treatment, and prevention of these encephalitis with emphasis on SSPE, and present some results from our group concerning pathogenesis and possible therapeutics approaches to this fatal disease.

Fig. 1. Neurological complications of Measles Virus Infections. Onset and time course of encephalitis after MV infection (ADEM, MIBE, and SSPE)
