Varicella-zoster virus at relapses of multiple sclerosis

Abstract

The possible participation of different herpes viruses was studied during exacerbations of multiple sclerosis (MS). We searched for the presence of DNA from the following herpes viruses: varicella zoster virus (VZV), herpes-simplex viruses 1 and 2; Epstein-Barr virus (EBV) and human herpes-virus-6 (HHV6) in mononuclear cells from patients with MS during relapse (n = 40), MS during remission (n = 131) and controls (n = 125). Additionally, immune cells containing viral antigens were quantified by flow cytometry, and VZV load was determined by real time PCR in 2 MS patients at various times during relapse and remission. DNA from VZV was found in 95% of MS patients during relapse and in 17% during remission; all controls were negative; by contrast, DNA from HHV6 was found in 24% of MS patients during relapse and in 2% during remission; DNA from herpes simplex viruses was not found in any subject; and DNA from EBV was found in a similar percentage of subjects from all groups. Sequential quantification of VZV-load showed a curve that increased during relapse and disappeared at remission. Also, VZV antigens were found inside a large number of immune cells from MS patients during relapse as compared with MS patients on remission and controls. In the typical forms of VZV infection, varicella and herpes-zoster, DNA from VZV is found in mononuclear cells exclusively during brief periods at the beginning of the active infection, but not during latency; thus, the conspicuous presence of VZV during relapses of MS may indicate a period of active infection and suggests the participation of VZV in the pathogenesis of MS.

Relation between Epstein-Barr virus and multiple sclerosis: analytic study of scientific production

“…When the presence of the virus DNA in total blood, cells, plasma, CSF or brain biopsy was analysed, only one of the studies found a relationship between the infection and the disease [40]. On the other hand, it is known that EBV DNA in serum is present in most patients in the acute phase of MS, as a consequence of the virus replication; however, during the latency stage, its detection in plasma or CSF is more difficult, although the higher viral load will be found in B lymphocytes [49].…”

“…In addition, Sanders et al [39] found a small proportion of positive cases in the brain tissue, with no differences between patients with active and inactive demyelinating plaques. Neither were there any differences when remittent or recurrent patients were considered [27,40]. However, lytic and latent infection markers have recently been found in the CSF of MS patients, in ectopic follicles [11].…”

“…Studies based on the detection of EBV DNA in serum [41], plasma [29] and mononuclear cells [20,27,28,40] (Table 6) found DNA, both in cases and in controls, but only showed OR: odds ratio; CI: confidence interval; S: selection; C: comparability; E: exposure OR: odds ratio; CI: confidence interval; S: selection; C: comparability; E: exposure a significant association between the virus and the disease in the study by Sotelo et al [40]. The study by Hay and Tenser [28] should be highlighted, with 100% positive results in both cases and controls.…”

Antibodies in multiple sclerosis oligoclonal bands target debris

“…Some earlier studies that evaluated whole CSF IgG from MS patients identified antibodies to several different viruses, such as measles, varicella zoster, human T-lymphocytic virus 1, and human hepatitis virus 6 (7), whereas other investigations found antibodies targeting major myelin proteins, myelin basic protein (MBP) and myelin oligodencrocyte glycoprotein (MOG) (8,9) as well as glycolipids, fatty acids, and neurofilament proteins (10). Similarly, more recent investigations that have applied single-cell PCR cloning to individual CSF B cells in MS have detected antibodies to certain viruses or myelin proteins (11)(12)(13). However, it has been impossible to match specificity of antibodies identified in CSF to OCB by studying whole CSF IgG or recombinant antibodies constructed from rearranged Ig heavy-and light-chain genes in individual B cells.…”

Mini review article. Human herpesvirus-6 and the etiology of multiple sclerosis: a literature review

“…Reports on the presence of HHV-6 DNA in peripheral blood mononuclear cells (PBMCs) or peripheral blood from healthy controls vary considerably. Sotelo et al [36] and Hon et al [37] reported HHV-6 DNA absent, Fredj et al [38] in 2.0%, Hay and Tenser, [35] in 14%, and Mameli et al [39] in 21.4% of healthy controls. lvarez-Lafuente et al [31], Alvarez-Lafuenteet al [40], and Chapenko et al [30] reported higher prevalence rates, 30.4%, 21.6%, and 28.7% respectively, while Ablashi et al [41] reported HHV-6 DNA in PBMCs from 60.0% of healthy controls.…”