Original Article

Degradation of Transcription Factor RFX5 during the Inhibition of both Constitutive and Interferon –inducible Major Histocompatibility Complex Class I Expression in Chlamydia-infected Cells

Correspondence to: Guangming Zhong, Dept. of Microbiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curve Dr., San Antonio, TX 78284-7758. Tel:210-567-1169 Fax:210-567-6612 E-mail:zhongg{at}uthscsa.edu.

We have previously shown that the obligate intracellular pathogen chlamydia can suppress interferon (IFN)-–inducible major histocompatibility complex (MHC) class II expression in infected cells by degrading upstream stimulation factor (USF)-1. We now report that chlamydia can also inhibit both constitutive and IFN-–inducible MHC class I expression in the infected cells. The inhibition of MHC class I molecule expression correlates well with degradation of RFX5, an essential downstream transcription factor required for both the constitutive and IFN-–inducible MHC class I expression. We further demonstrate that a lactacystin-sensitive proteasome-like activity identified in chlamydia-infected cell cytosolic fraction can degrade both USF-1 and RFX5. This proteasome-like activity is dependent on chlamydial but not host protein synthesis. Host preexisting proteasomes may not be required 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. These findings provide novel information on the molecular mechanisms of chlamydial evasion of host immune recognition.

Key Words: MHC class I suppression, RFX5 degradation, IFN- induction, chlamydial infection, proteasomal activity

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