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1994-08-27
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Document 0716
DOCN M9480716
TI Cytomegalovirus infection of human retinal tissue: an in vivo model.
DT 9410
AU DiLoreto D Jr; Epstein LG; Lazar ES; Britt WJ; del Cerro M; Department
of Neurobiology and Anatomy, University of Rochester; School of
Medicine, New York.
SO Lab Invest. 1994 Jul;71(1):141-8. Unique Identifier : AIDSLINE
MED/94315864
AB BACKGROUND: Cytomegalovirus (CMV) retinitis is a common, devastating
complication of AIDS. Strict host specificity of human CMV (HCMV), has
limited the study of the virus. The purpose of this research was to
create a model that allowed the in vivo infection of human retinal
tissue with HCMV. EXPERIMENTAL DESIGN: Small fragments of 13-week human
fetal retina were transplanted into the anterior chambers of
immune-deficient mice. One week later, 15 of 30 grafts were inoculated
with HCMV. Infected and noninfected specimens were compared for
histopathologic changes at 14, 30, and 60 days at light and electron
microscopic levels. Histochemistry was performed to characterize: level
of graft differentiation, range of viral replication cycle, and effects
on neuronal, glial, and monocytic elements of the retina. RESULTS: At 30
and 60 days, grafts were well differentiated histologically and
histochemically. The infected grafts showed numerous large cells
containing intranuclear and intracytoplasmic inclusions. Ultrastructural
examination revealed viral particles within cytoplasm and nuclei.
Infected cells expressed proteins representative of all phases of the
HCMV replication cycle. Most HCMV-infected cells expressed the neuronal
marker, protein gene product 9.5. In a second series of experiments,
tissue from one graft harvested at 45 days postinfection was used to
recover HCMV in fibroblast cultures and also used successfully to
passage the virus to two control grafts. CONCLUSIONS: This model allows
HCMV to actively infect and replicate within highly differentiated human
neural tissue. It produces pathology characteristic of CMV-infected
neural tissue in a time course suitable for long-term study. The nature
of this model will allow the study of: the replication properties of
HCMV in nervous tissue, the specific effects of HCMV on the human
retina, the interaction of HCMV with other viruses, e.g., HIV, and
various anti-viral therapies.
DE Animal *Cytomegalovirus Infections/MICROBIOLOGY/PATHOLOGY Disease
Models, Animal Fetal Tissue Transplantation Human Mice Mice, SCID
Microscopy, Electron Retina/*EMBRYOLOGY/MICROBIOLOGY/PATHOLOGY
*Retinal Diseases/MICROBIOLOGY/PATHOLOGY Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S. Transplantation, Heterologous Virus
Replication JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).