Pathogenic potentials of glycoprotein C-negative syncytial mutants from rabbit T cells infected persistently with herpes simplex virus type 1

• Published in: Journal of medical virology Vol. 76; no. 1; pp. 89 - 97
• Main Authors: Ishida, Yoshimasa, Okabe, Tomoyuki, Azukizawa, Yoshimi, Isono, Takahiro, Seto, Akira
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.05.2005; Wiley-Liss
• Subjects: Adrenal Glands - virology; Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; CD8-Positive T-Lymphocytes; Cell Line, Transformed; Cytopathogenic Effect, Viral; Fundamental and applied biological sciences. Psychology; Giant Cells - pathology; glycoprotein C; Herpes Simplex - pathology; Herpesvirus 1, Human - genetics; Herpesvirus 1, Human - immunology; Herpesvirus 1, Human - pathogenicity; HSV-1; Human viral diseases; Infectious diseases; Medical sciences; Microbiology; Miscellaneous; Molecular Sequence Data; mutant; Mutation; pathogenicity; persistent infection; rabbit; Rabbits; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Sequence Alignment; syncytium; T cell; Time Factors; Viral diseases; Viral Envelope Proteins - analysis; Viral Envelope Proteins - genetics; Virology; Virulence; syncytium; HSV- 1; Herpesviridae; T cell; glycoprotein C; Alphaherpesvirinae; Glycoprotein; Rabbit; Lagomorpha; Virus; Pathogenicity; Vertebrata; Mammalia; Persistent infection; T-Lymphocyte; Human herpesvirus 1; Infected cell; Mutation; mutant
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.20328

Human T cell lymphotropic virus type I (HTLV‐I)‐transformed T cells of rabbits were infected persistently with Herpes simplex virus type 1 (HSV‐1) strain KOS. These infected cells yielded syncytial mutants, either glycoprotein C (gC)‐negative or ‐positive, which predominated over and replaced the wild‐type virus in a long‐term culture for 2 years. An alignment of nucleotide sequences showed multiple mutations in glycoprotein B (gB) and gC genes of these mutants, which are or may be responsible for the mutant phenotypes. One of four mutants analyzed produced extensively large syncytia and possessed point mutations within the cytoplasmic domain of gB. All four mutants possessed multiple point mutations in gC and two possessed single insertions which resulted in a frame shift, leading to the premature termination of the gC polypeptide chain. The supernatant of the 2‐year culture of cells infected persistently, containing only gC‐negative syncytial mutants, induced encephalitic symptoms in B/Jas inbred rabbits, when injected intravenously. One gC‐negative syncytial isolate from an encephalitic lesion, together with those from the culture supernatant, were examined for pathogenic potential in vitro and in vivo. All these mutants were more cytotoxic and more susceptible to complement inactivation than the parental virus, and could infect and replicate in adrenal glands when injected intravenously into rabbits. Invasion into the central nervous system appeared to be blocked at the portal of entry, the adrenal gland, i.e., none exhibited neuroinvasive potential by itself. Syncytial gC‐negative mutants could thus be pathogenic in rabbits. J. Med. Virol. 76:89–97, 2005. © 2005 Wiley‐Liss, Inc.