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Replication of human cytomegalovirus in severe combined immunodeficient mice implanted with human retinal tissue
D J Bidanset1, R J Rybak, C B Hartline
1Department of Pediatrics, University of Alabama School of Medicine, Birmingham, AL 35294, USA. Debbie@uab.edu
Abstract:
Because human cytomegalovirus (HCMV) infection and replication are limited to human cells, few animal models can be used to specifically examine the biology of HCMV in vivo. In these studies, fetal human retinal tissue was implanted into the anterior chamber of the severe combined immunodeficient (SCID) mouse eye and subsequently was inoculated with HCMV. Viral replication, localized to glial cells in the xenografts, was first detected 7 days after infection. Thereafter, HCMV replication increased to peak levels through days 21-28 and then gradually decreased to undetectable levels by 8 weeks after infection. The clinical isolate Toledo replicated to higher titers than did strain AD169 or Towne. A comparison of implant age indicated that older tissue could support higher levels of HCMV replication than could younger implants. SCID mice implanted with human retinal tissue provide an excellent model for evaluation of HCMV infection of an ocular structure in vivo.
Insights
A novel SCID mouse model using human retinal tissue xenografts allows in vivo study of human cytomegalovirus (HCMV) ocular infection. This model effectively replicates HCMV, aiding research into viral disease.
Area of Science:
- Virology
- Immunology
- Ophthalmology
Background:
- Human cytomegalovirus (HCMV) infection is restricted to human cells, limiting in vivo study.
- Existing animal models are insufficient for examining HCMV biology in a living organism.
Purpose of the Study:
- To develop and validate a severe combined immunodeficient (SCID) mouse model for studying HCMV ocular infection in vivo.
- To evaluate HCMV replication dynamics and influencing factors within human retinal xenografts.
Main Methods:
- Fetal human retinal tissue was xenografted into the anterior chamber of SCID mouse eyes.
- Xenografts were inoculated with HCMV (clinical isolate Toledo, AD169, or Towne strains).
- Viral replication was monitored over 8 weeks using quantitative methods.
Main Results:
- HCMV replication was detected in glial cells of retinal xenografts, peaking between days 21-28 post-infection.
- The clinical isolate Toledo demonstrated higher replication titers compared to AD169 and Towne strains.
- Older retinal tissue supported significantly higher levels of HCMV replication than younger tissue.
Conclusions:
- SCID mice bearing human retinal xenografts provide a robust and relevant model for in vivo HCMV ocular infection.
- This model facilitates the investigation of HCMV pathogenesis and replication within ocular tissues.
- Implant age is a critical factor influencing HCMV replication in this xenograft model.