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Dramatic interstrain differences in the replication of human cytomegalovirus in SCID-hu mice
J M Brown1, H Kaneshima, E S Mocarski
1Department of Microbiology, Stanford University School of Medicine, CA 94305-5402, USA.
Abstract:
The ability of a low-passage strain (Toledo) and laboratory strains (AD169 and Towne) of human cytomegalovirus to replicate in SCID-hu (thymus plus liver) mice were compared. At a time of peak replication, 14 days after inoculation, the Toledo strain grew 2-3 orders of magnitude better than any laboratory strain, a difference reflecting the number of infected thymic stromal cells in the implants. The growth property of the Toledo strain was stable through serial passage and plaque purification. The AD169-ATCC strain failed to grow at all, while an independently maintained stock of this strain obtained from the United Kingdom replicated to low levels, suggesting that divergence had occurred during propagation in different locations. This work predicts the existence of viral genetic determinant(s) for growth in tissues that are lost during propagation in culture.
Insights
The Toledo strain of human cytomegalovirus replicates significantly better in SCID-hu mice than lab strains. This suggests tissue-specific growth factors are lost during cell culture adaptation.
Area of Science:
- Virology
- Immunology
- Animal Models
Background:
- Human cytomegalovirus (HCMV) is a widespread pathogen.
- Laboratory strains (AD169, Towne) are widely used but may have altered properties.
- SCID-hu mice (thymus and liver) provide a model for human tissue infection.
Purpose of the Study:
- To compare the replication of a low-passage HCMV strain (Toledo) versus laboratory strains (AD169, Towne) in SCID-hu mice.
- To investigate viral determinants of tissue tropism and replication.
Main Methods:
- Inoculation of SCID-hu mice with Toledo, AD169-ATCC, and AD169-UK strains of HCMV.
- Quantification of viral replication at peak levels (14 days post-inoculation).
- Assessment of viral genetic stability through serial passage and plaque purification.
Main Results:
- The Toledo strain demonstrated 2-3 orders of magnitude greater replication than laboratory strains.
- Replication differences correlated with the number of infected thymic stromal cells.
- AD169-ATCC failed to replicate, while AD169-UK showed low-level replication, indicating strain divergence.
Conclusions:
- Low-passage HCMV strains exhibit superior replication in human tissues compared to adapted laboratory strains.
- Tissue-specific growth determinants are likely lost during prolonged cell culture.
- Further research into viral genetic factors influencing HCMV tissue tropism is warranted.