Role of Viruses in the Pathogenesis of Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is an immune inflammatory disease, where the underlying etiological cause remains elusive. Multiple triggering factors have been suggested, including environmental, genetic and gender components. However, underlying infectious triggers to the disease are also suspected. There is an increasing abundance of evidence supporting a viral etiology to MS, including the efficacy of interferon therapy and over-detection of viral antibodies and nucleic acids when compared with healthy patients. Several viruses have been proposed as potential triggering agents, including Epstein-Barr virus, human herpesvirus 6, varicella-zoster virus, cytomegalovirus, John Cunningham virus and human endogenous retroviruses. These viruses are all near ubiquitous and have a high prevalence in adult populations (or in the case of the retroviruses are actually part of the genome). They can establish lifelong infections with periods of reactivation, which may be linked to the relapsing nature of MS. In this review, the evidence for a role for viral infection in MS will be discussed with an emphasis on immune system activation related to MS disease pathogenesis.

Keywords: Epstein–Barr virus; John Cunningham virus; cytomegalovirus; human endogenous retroviruses; human herpesvirus 6; multiple sclerosis; varicella–zoster virus.

Figure 1

Clinical presentation of multiple sclerosis (MS). Relapsing–remitting MS (RRMS)—has worsening of clinical symptoms followed by periods of recovery; primary progressive MS (PPMS)—has steady progression of clinical symptoms; secondary progressive MS (SPMS)—initial relapsing–remitting course followed by steady progression of symptoms; and progressive relapsing MS (PRMS)—steady progression of clinical symptoms with occasional relapses.

Figure 2

Myelin-associated glycoprotein (MOG) expression on the surface of the myelin, covering the axon. The myelin sheets are held together with Myelin basic protein (MBP), while MOG is located on the surface and exposed to the autoreactive leukocytes.

Figure 3

The structure of herpesviruses. The viral DNA is packed inside the capsid, which is wrapped by the tegument. The envelope, the outer layer of the virion, is composed of the phospholipids bilayer embedded with glycoproteins.

Figure 4

The structure of the John Cunningham virus (JCV). The viral DNA is packed around the histones in a chromatin-like complex. It is covered by viral structural proteins VP1, forming the capsid with the VP2 and VP3 proteins incorporated.