Analysis of human cytomegalovirus US3 gene products.

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.