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Analysis of human cytomegalovirus US3 gene products
Wenzhong Liu1, Yiqiang Zhao, Bonita Biegalke
1Graduate Program in Giological Sciences, Department of Biomedical Sciences, Ohio Unversity College of Osteopathic Medicine, Athens, Ohio 45701, USA.
Abstract:
Similar to other herpesviruses, human cytomegalovirus remains in the infected host following resolution of the primary infection. The ability to persist in the host after primary infection is believed to be strongly influenced by the ability of HCMV to down-regulate immune recognition of infected cells. One of the genes contributing to immune evasion is the US3 gene. The US3 gene has been shown to retain major histocompatibility complex type I molecules in the endoplasmic reticulum. The US3 gene gives rise to three alternatively spliced RNAs which encode distinct but related proteins. Each of the alternatively spliced transcripts is present early in viral infection, suggesting that the encoded proteins play a role in the viral life cycle. We demonstrate that only the protein encoded by the unspliced US3 transcript is able to retain MHC class I heavy chains in the endoplasmic reticulum. The protein encoded by the singly spliced US3 transcript appears to be processed through the secretory pathway while the protein encoded by the doubly spliced transcript becomes localized to the Golgi apparatus. These experiments raise interesting questions about the functions of the smaller US3 proteins during viral infection in the host.
Insights
Human cytomegalovirus (HCMV) evades immune detection using its US3 gene. Only the unspliced US3 protein effectively retains MHC class I in the endoplasmic reticulum, aiding viral persistence.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Human cytomegalovirus (HCMV) establishes lifelong infections by evading host immune responses.
- Immune evasion is crucial for HCMV persistence after primary infection.
- The HCMV US3 gene is implicated in down-regulating immune recognition.
Purpose of the Study:
- To investigate the distinct functions of proteins encoded by alternatively spliced US3 transcripts.
- To determine which US3 protein isoform is responsible for retaining MHC class I in the endoplasmic reticulum.
Main Methods:
- Analysis of alternatively spliced US3 transcripts and their encoded proteins.
- Localization studies of US3 proteins within infected cells.
- Assessment of MHC class I heavy chain retention in the endoplasmic reticulum.
Main Results:
- The unspliced US3 protein retains MHC class I heavy chains in the endoplasmic reticulum.
- The singly spliced US3 protein is processed via the secretory pathway.
- The doubly spliced US3 protein localizes to the Golgi apparatus.
Conclusions:
- HCMV US3 gene products exhibit differential localization and function.
- The unspliced US3 protein plays a key role in HCMV immune evasion by inhibiting MHC class I presentation.
- The functions of smaller US3 proteins during HCMV infection require further investigation.