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Evaluation of the antiviral potential of the soluble forms of glycoprotein D receptors on ocular herpes caused by HSV‐1 and HSV‐2 infections in a transgenic mouse model
Author(s) -
Fujimoto Yoshikazu,
Hikita Shinichi,
Takeda Keiko,
Ozaki Kinuyo,
Inoue Hideya,
Takakuwa Hiroki,
Sonoda Kohhei,
Ono Etsuro
Publication year - 2019
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.25384
Subject(s) - herpes simplex virus , virology , vero cell , virus , genetically modified mouse , transgene , biology , in vivo , in vitro , immunology , gene , biochemistry , microbiology and biotechnology
Ocular herpes, caused by herpes simplex virus type 1 (HSV‐1) and type 2 (HSV‐2) infections, remains an important corneal disease, which may result in loss of vision. Because the frequency of acyclovir resistance in HSV has increased, novel antiviral agents are needed for therapeutic approaches to ocular herpes. Several studies have demonstrated that fusion proteins containing entire ectodomain of HSV glycoprotein D receptors, including herpesvirus entry mediator A (HVEM), nectin‐1 and nectin‐2, and the Fc portion of human IgG (HVEMIg, nectin‐1Ig, and nectin‐2Ig, respectively), can exert antiviral effects in vitro and in vivo. Here, to evaluate the antiviral potential of HVEMIg, nectin‐1Ig, and nectin‐2Ig against ocular infections with HSV, transgenic mice expressing these fusion proteins were ocularly inoculated with HSV‐1 and HSV‐2. Transgenic mouse lines expressing HVEMIg and nectin‐1Ig showed marked resistance to ocular herpes; on the other hand, mouse lines expressing nectin‐2Ig did not. Furthermore, to investigate the therapeutic effects of nectin‐1Ig, which can neutralize HSVs in vitro against ocular disease, transgenic mouse serum containing nectin‐1Ig was dropped into the eyes of wild‐type mice after HSV infection. Reduction of severe symptoms could be observed in mice treated with nectin‐1Ig serum. These results warrant further study of soluble HVEM and nectin‐1 products as preventive and therapeutic agents against ocular herpes caused by HSV‐1 and HSV‐2 infections, especially nectin‐1Ig as a new eye drop.