Role of herpes simplex virus 1 Us3 in viral neuroinvasiveness

Authors

  • Naoto Koyanagi,

    1. Division of Molecular Virology, Department of Microbiology and Immunology
    2. Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-Ku, Tokyo, Japan
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  • Takahiko Imai,

    1. Division of Molecular Virology, Department of Microbiology and Immunology
    2. Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-Ku, Tokyo, Japan
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  • Jun Arii,

    1. Division of Molecular Virology, Department of Microbiology and Immunology
    2. Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-Ku, Tokyo, Japan
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  • Akihisa Kato,

    1. Division of Molecular Virology, Department of Microbiology and Immunology
    2. Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-Ku, Tokyo, Japan
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  • Yasushi Kawaguchi

    Corresponding author
    1. Division of Molecular Virology, Department of Microbiology and Immunology
    2. Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-Ku, Tokyo, Japan
    • Correspondence

      Yasushi Kawaguchi, Division of Molecular Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan. Tel: +81 3 6409 2070; fax: +81 3 6409 2072; email: ykawagu@ims.u-tokyo.ac.jp

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ABSTRACT

Us3 is a serine–threonine protein kinase that is encoded by herpes simplex virus 1 (HSV-1). In experimental animal models of HSV infection, peripheral and intracranial inoculations can be used to study viral pathogenicity in peripheral sites (e.g., eyes and vagina) and central nervous systems (CNSs), respectively. In addition, peripheral inoculation can be used to investigate this virus' ability to invade the CNS (neuroinvasiveness) from peripheral sites. HSV-1 Us3 has previously been shown to be critical for viral pathogenicity in both peripheral sites and CNSs of mice. However, the role of HSV-1 Us3 in viral neuroinvasiveness has not yet been elucidated. In the present study, the yields of a Us3 null mutant virus and its repaired virus in the eyes, trigeminal ganglia, and brains of mice following ocular inoculation were examined. It was found that, although the repaired virus appeared in the brains of mice 3 days after infection, peak replication occurring 7 days after infection, no viral replication of the Us3 null mutant virus was detectable. These findings indicate that HSV-1 Us3 plays a crucial role in the ability of the virus to invade the brain from the eyes. Thus, HSV-1 Us3 is a significant neuroinvasiveness factor in vivo.

Ancillary