Dual impacts of a glycan shield on the envelope glycoprotein B of HSV-1: evasion from human antibodies in vivo and neurovirulence

Author:

Fukui Ayano12ORCID,Maruzuru Yuhei123ORCID,Ohno Shiho4,Nobe Moeka12,Iwata Shuji12,Takeshima Kosuke12,Koyanagi Naoto123,Kato Akihisa123,Kitazume Shinobu5,Yamaguchi Yoshiki4,Kawaguchi Yasushi1236ORCID

Affiliation:

1. Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo , Tokyo, Japan

2. Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo , Tokyo, Japan

3. Research Center for Asian Infectious Diseases, The Institute of Medical Science, The University of Tokyo , Tokyo, Japan

4. Division of Structural Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University , Miyagi, Japan

5. Department of Clinical Laboratory Sciences, School of Health Sciences, Fukushima Medical University , Fukushima, Japan

6. The University of Tokyo, Pandemic Preparedness, Infection and Advanced Research Center , Tokyo, Japan

Abstract

ABSTRACT Identification of the mechanisms of viral evasion from human antibodies is crucial both for understanding viral pathogenesis and for designing effective vaccines. Here we show in cell cultures that an N-glycan shield on the herpes simplex virus 1 (HSV-1) envelope glycoprotein B (gB) mediated evasion from neutralization and antibody-dependent cellular cytotoxicity due to pooled γ-globulins derived from human blood. We also demonstrated that the presence of human γ-globulins in mice and immunity to HSV-1 induced by viral infection in mice significantly reduced replication in their eyes of a mutant virus lacking the glycosylation site but had little effect on the replication of its repaired virus. These results suggest that an N-glycan shield on a specific site of HSV-1 envelope gB mediated evasion from human antibodies in vivo and from HSV-1 immunity induced by viral infection in vivo . Notably, we also found that an N-glycan shield on a specific site of HSV-1 gB was significant for HSV-1 neurovirulence and replication in the central nervous system of naïve mice. Thus, we have identified a critical N-glycan shield on HSV-1 gB that has dual impacts, namely evasion from human antibodies in vivo and viral neurovirulence. IMPORTANCE Herpes simplex virus 1 (HSV-1) establishes lifelong latent and recurrent infections in humans. To produce recurrent infections that contribute to transmission of the virus to new human host(s), the virus must be able to evade the antibodies persisting in latently infected individuals. Here, we show that an N-glycan shield on the specific site of the envelope glycoprotein B (gB) of HSV-1 mediates evasion from pooled γ-globulins derived from human blood both in cell cultures and mice. Notably, the N-glycan shield on the specific site of gB was also significant for HSV-1 neurovirulence in naïve mice. Considering the clinical features of HSV-1 infection, these results suggest that the glycan shield not only facilitates recurrent HSV-1 infections in latently infected humans by evading antibodies but is also important for HSV-1 pathogenesis during the initial infection.

Funder

MEXT | Japan Society for the Promotion of Science

MEXT | Japan Science and Technology Agency

Japan Agency for Medical Research and Development

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

Reference77 articles.

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