Human Herpesvirus 6 Genome and Antigen in Acute Multiple Sclerosis Lesions
http://www.medscape.com/viewarticle/457184_2
Infectious Diseases, July 2003 Journal Scan
Medscape Infectious Diseases 5(2), 2003.
The Journal of Infectious Diseases
May 1, 2003 (Volume 187, Number 9)
Goodman AD, Mock DJ, Powers JM, Baker JV, Blumberg BM
The Journal of Infectious Diseases. 2003;187(9):1365-1376
Multiple sclerosis (MS) remains a heartbreaking disease without clear etiology. Nevertheless, there have been important strides in therapy, offering hope to thousands with the illness. Such therapies have been developed on animal models of autoimmune demyelinative encephalitis. The trigger of this process has been thought for years to be 1 or more viral agent. Recent reports have suggested a role of Epstein Barr virus (EBV)[1] and other ubiquitous herpesviruses such as human herpesvirus 6 (HHV-6). This report extends the evidence that latent HHV-6 infection of brain oligodendrocytes, lymphocytes, and microglia is associated with acute manifestations of the disease.
The investigators, from the University of Rochester (New York), obtained brain biopsies from 5 patients with acute MS. These patients were atypical in that they presented acutely and within weeks in most cases had craniotomy for diagnosis of a brain tumor. The biopsies demonstrated inflammatory lesions with demyelination, and the subsequent course of each patient was more consistent with MS. The investigators used a 2-step in situ polymerase chain reaction (ISPCR) technique to demonstrate HHV-6 genome in formalin-fixed archival tissue. Immunocytochemical (ICC) staining was attempted to demonstrate HHV-6 antigens, including gp116. Specific cells were type-identified by histologic appearance. Unfortunately, no control tissue is reported.
Each of 9 pathologic specimens from the 5 patients demonstrated positive ISPCR in oligodendrocytes, lymphocytes, and glial/macrophage cells in the involved tumor. ICC stains were either weakly reactive in a variety of cells other than oligodendrocytes or were negative.
A companion article in the same issue used laser microdissection of formalized tissue from patients with MS and controls, then amplified extracted DNA for HHV-6 by nested PCR.[2] In this study, plaques from MS patients were much more likely to demonstrate HHV-6 genetic material (57.8%) than normal-appearing tissue (15.9%) or tissue from control patients (21.7% to 26.8%). The accompanying editorial[3] provides an excellent review of the biology of HHV-6 and the difficulty in attributing causation based on these and other studies.
These reports seem to add evidence of HHV-6 playing a role in the etiology of MS. Since this is a ubiquitous virus, the host immune response must be important in disease causation as well. Genetic susceptibility might explain the peculiar north-south distribution of the disease, as well as its exceptions, such as Key West, Florida, if a Scandinavian/Celtic heritage were associated with specific major histocompatibility complexes or other genetic variations. These articles seem to bring us a tiny step closer to understanding and possibly treating or preventing this disease.
Levin LI, Munger KL, Rubertone MV, et al. JAMA. 2003;289:1533-1536. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12672770&dopt=Abstract
Cermelli C, Berti R, Soldan SS, et al. High frequency of human herpesvirus 6 DNA in multiple sclerosis plaques isolated by laser microdissection. J Infect Dis. 2003;187:1377-1387. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12717618&dopt=Abstract
Tyler KL. Human herpesvirus 6 and multiple sclerosis: the continuing conundrum. J Infect Dis. 2003;187:1360-1364. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&list_uids=12717616&dopt=Abstract
Copyright © 2003, Medscape