Document 0533
 DOCN  M9460533
 TI    A thymidine kinase-negative HSV-1 strain establishes a persistent
       infection in SCID mice that features uncontrolled peripheral replication
       but only marginal nervous system involvement.
 DT    9404
 AU    Valyi-Nagy T; Gesser RM; Raengsakulrach B; Deshmane SL; Randazzo BP;
       Dillner AJ; Fraser NW; Wistar Institute, Philadelphia, Pennsylvania
       19104.
 SO    Virology. 1994 Mar;199(2):484-90. Unique Identifier : AIDSLINE
       MED/94167886
 AB    A detailed knowledge of the pathogenesis of infections caused by
       thymidine-kinase (TK)-deficient herpes simplex virus type 1 (HSV-1)
       strains is important because such mutants can arise during treatment of
       HSV infections with acyclovir--especially in immunocompromised
       patients--and also because TK-negative mutants may become useful for the
       therapy of intracranial tumors. In this work, we studied the
       pathogenesis of a genetically engineered TK-negative HSV-1 strain
       dlsptk, in SCID mice (mice with severe combined immunodeficiency) after
       corneal infection. We found that dlsptk established a persistent
       infection that kills SCID mice within 80.2 +/- 21.3 days. The cause of
       death seemed to be related to uncontrolled viral replication in the
       superficial and deep facial tissues of the animals. Viremia probably did
       not occur, as judged by the inability to detect infectious virus and
       viral gene expression in various internal organs. However, the virus did
       reach the nervous system, most probably by axonal transport from the
       primary site of the infection. Virus-specific DNA reached low but
       detectable levels in the trigeminal ganglia and the brainstems by 7 days
       p.i. and remained at low levels for up to 50 days p.i. as determined by
       spot blot analysis. By in situ hybridization and immunostaining we
       determined that, in some of the neurons of the trigeminal ganglia
       infected by the virus, viral latency was established. However, our
       results suggested that in other infected neurons viral replication
       occurred and virus spread to surrounding nonneuronal cells and to the
       central nervous system. This work provides a new model in which the
       pathogenesis of infections caused by TK-deficient HSV strains in
       immunocompromised hosts can be effectively studied and which may also
       help to identify the potential side effects of the therapy of
       intracranial tumors with TK-negative HSV strains.
 DE    Animal  Disease Models, Animal  Herpes Simplex/*MICROBIOLOGY
       Herpesvirus 1, Human/ENZYMOLOGY/PHYSIOLOGY/*PATHOGENICITY  Mice  Mice,
       Inbred BALB C  Mice, SCID  Neurons/*MICROBIOLOGY  Support, U.S. Gov't,
       P.H.S.  Thymidine Kinase/*PHYSIOLOGY  Virus Replication/*PHYSIOLOGY
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).