Antibody to varicella-zoster virus immediate-early protein 62 augments allodynia in zoster via brain-derived neurotrophic factor.
Varicella-zoster virus (VZV) expresses immediate-early protein 62 (IE62), and zoster is associated with neuropathic pain. Brain-derived neurotrophic factor (BDNF) is involved in the neuronal mechanism underlying pain hypersensitivity. Zoster is associated with prodrome and the robust production of booster antibody to VZV. We hypothesized that the intrathecal production of antibody to IE62 cross-reacting with BDNF and the nerve injury by skin lesions may augment allodynia in zoster by enhancing BDNF activity. One of three monoclonal antibodies against the 268-556 peptide of IE62 recognized BDNF. Immunological cross-reactivity between IE62 and BDNF and the effects of anti-IE62 monoclonal antibody (anti-IE62 MAb) cross-reactivity with BDNF on BDNF activity in cultured neurons were examined. Anti-IE62 MAb and anti-BDNF MAbs recognized the 414-429 peptide of IE62 and the BDNF dimer. Anti-IE62 MAb significantly augmented BDNF-related transcription in neurons and the morphological development of spinal dorsal horn neurons. Sera from patients recognized IE62 and BDNF and enhanced BDNF activity in neurons. The effect of anti-IE62 antibody on mechanical allodynia was characterized by the threshold of allodynia using von Frey filaments in a spinal nerve injury (SNI) in mice. The administration of anti-IE62 MAb to or immunization with cross-reacting IE62 protein to mice significantly enhanced mechanical allodynia on the side with SNI but not on the uninjured side. Anti-IE62 antibody augmented BDNF activity in neurons and allodynia in mice with SNI. The intrathecal production of anti-IE62 antibody augmenting BDNF activity and peripheral nerve injury by zoster may participate in the pathogenesis of allodynia in zoster.
Hama
Yuka
Y
Department of Virology, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Shiraki
Kimiyasu
K
Yoshida
Yoshihiro
Y
Maruyama
Atsushi
A
Yasuda
Makoto
M
Tsuda
Masaaki
M
Honda
Mariko
M
Takahashi
Michiaki
M
Higuchi
Hiroshi
H
Takasaki
Ichiro
I
Daikoku
Tohru
T
Tsumoto
Tadaharu
T
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001483:Base Sequence; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D002460:Cell Line; D003429:Cross Reactions; D017931:DNA Primers; D006562:Herpes Zoster / Q000276:immunology*; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000276:immunology; D015534:Trans-Activators / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D000914:Antibodies, Viral; D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; C074221:IE62 protein, Human herpesvirus 3; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D014759:Viral Envelope Proteins