Degradation of transcription factor RFX5 during the inhibition of both constitutive and interferon gamma-inducible major histocompatibility complex class I expression in Chlamydia-infected cells

We have previously shown that the obligate intracellular pathogen chlamydia can suppress interferon (IFN)-gamma-inducible major histocompatibility com plex (MHC) class II expression in infected cells by degrading upstream stim ulation factor (USF)-1. We now report that chlamydia can also inhibit both constitutive and IFN-gamma-inducible MHC class I expression in the infected cells. The inhibition of MHC class I molecule expression correlates well w ith degradation of RFX5, an essential downstream transcription factor requi red for both the constitutive and IFN-gamma-inducible MHC class I expressio n. We further demonstrate that a lactacystin-sensitive proteasome-like acti vity identified in chlamydia-infected cell cytosolic fraction can degrade b oth USF-1 and RFX5. This proteasome-like activity is dependent on chlamydia l but not host protein synthesis. Host preexisting proteasomes may not be r equired for the unique proteasome-like activity. These observations suggest that chlamydia-secreted factors may directly participate in the proteasome -like activity. Efforts to identify the chlamydial factors are underway. Th ese findings provide novel information on the molecular mechanisms of chlam ydial evasion of host immune recognition.