ORF7 of varicella-zoster virus is a neurotropic factor.
Varicella-zoster virus (VZV) is the causative agent of chickenpox and herpes zoster (shingles). After the primary infection, the virus remains latent in sensory ganglia and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding skin tissue. The current varicella vaccine is highly attenuated in the skin and yet retains its neurovirulence and may reactivate and damage sensory neurons. The factors involved in neuronal invasion and establishment of latency are still elusive. Previously, we constructed a library of whole-gene deletion mutants carrying a bacterial artificial chromosome sequence and a luciferase marker in order to perform a comprehensive VZV genome functional analysis. Here, screening of dispensable gene deletion mutants in differentiated neuronal cells led to the identification of ORF7 as the first known, likely a main, VZV neurotropic factor. ORF7 is a virion component localized to the Golgi compartment in infected cells, whose deletion causes loss of polykaryon formation in epithelial cell culture. Interestingly, ORF7 deletion completely abolishes viral spread in human nervous tissue ex vivo and in an in vivo mouse model. This finding adds to our previous report that ORF7 is also a skin-tropic factor. The results of our investigation will not only lead to a better understanding of VZV neurotropism but could also contribute to the development of a neuroattenuated vaccine candidate against shingles or a vector for delivery of other antigens.
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA.
Anca
A
Selariu
Tong
T
Cheng
Qiyi
Q
Tang
Benjamin
B
Silver
Lianwei
L
Yang
Che
C
Liu
Xiangzhong
X
Ye
Amos
A
Markus
Ronald S
RS
Goldstein
Ruth S
RS
Cruz-Cosme
Yanzhen
Y
Lin
Lanling
L
Wen
Hongliu
H
Qian
Jinle
J
Han
Kalpana
K
Dulal
Ying
Y
Huang
Yimin
Y
Li
Ningshao
N
Xia
Hua
H
Zhu
D000818:Animals; D004195:Disease Models, Animal; D017353:Gene Deletion; D006562:Herpes Zoster / Q000473:pathology / Q000821:virology; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000821:virology*; D009924:Organ Culture Techniques; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
C553585:ORF7 protein, human herpesvirus 3; D014764:Viral Proteins; D037521:Virulence Factors