Reactivation of human herpesvirus-6 in natalizumab treated multiple sclerosis patients.
The alpha(4) integrin antagonist natalizumab was shown to be effective in patients with immune-mediated disorders but was unexpectedly associated with JC polyomavirus associated progressive multifocal leukoencephalopathy (PML) in two multiple sclerosis (MS) and one Crohn's disease patients. Impaired immune surveillance due to natalizumab treatment may have contributed to the JCV reactivation. As HHV-6 has been suggested to play a role in MS, we asked whether this virus could also have been reactivated during natalizumab therapy. Matched sera and CSF from a limited set of MS patients treated with and without natalizumab were examined for evidence of HHV-6. In addition, we also superinfected a persistent JC virus infected glial cell with HHV-6A to determine if JC virus can be increased. Elevated serum HHV6 IgG and HHV-6A DNA was detected in the CSF of a subset of patients but not controls. We confirmed that superinfection with HHV-6 of a JC virus infected glial cells increased expression of JCV. These results support the hypothesis that treatment with natalizumab may be associated with reduced immune surveillance resulting in reactivation of viruses associated with MS pathogenesis.
Yao
Karen
K
Viral Immunology Section, National Institutes of Health, Bethesda, Maryland, United States of America.
Gagnon
Susan
S
Akhyani
Nahid
N
Williams
Elizabeth
E
Fotheringham
Julie
J
Frohman
Elliot
E
Stuve
Olaf
O
Monson
Nancy
N
Racke
Michael K
MK
Jacobson
Steven
S
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D002460:Cell Line; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D015654:Herpesvirus 6, Human / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid; D007577:JC Virus / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000821:virology*; D000069442:Natalizumab; D019349:Roseolovirus Infections / Q000821:virology; D015854:Up-Regulation / Q000187:drug effects; D014775:Virus Activation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; D004279:DNA, Viral; D007074:Immunoglobulin G; D000069442:Natalizumab