*2.3.1 CPAF*

CPAF factor responsible for chlamydial protease/proteasome-like activity is highly conserved [1]. It acts as a zymogen, which means it can self-activate and auto-process

via vicinity-dependent homodimerization [1]. It is a secreted serine protease known to cleave a large amount of host proteins. Its role has been described in attacking certain host mechanisms to evade the immune system and to survive and replicate intracellularly. Their targets are the host transcriptional factors USF-1 23, RFX5 24, NF-κB, and HIF-1, the proapoptotic BH3-only proteins, the DNA repairing Poly-ADP-ribose polymerase, cyclin B1, cytoskeleton proteins involved in cell structure like keratin 8, keratin 18 and vimentin, and proteins involved in repairment of Golgi apparatus, proteins involved in cell adhesion like nectin-1 [1, 13]. The secreted CPAF into the cytoplasm of the infected cell degrades the transcription factors RFX5 and USF-1 that are responsible for MHC gene activation. In this way, the microorganism reduces immune recognition by affecting antigen presentation and suppressing IFNγinducible MHC class I expression [1, 13]. BH3-only proteins like Puma and Bim that act as intracellular stress sensor molecules via migration to the mitochondria induce apoptosis. The mechanism involves the activation of the multi-domain proapoptotic Bax and Bak to suppress the antiapoptotic function of BcL-2. CPAF degrades the BH3-only domain proteins and acts in favor of antiapoptotic activity. This mechanism still needs elucidation [1, 13]. Another distinct role of CPAF is cleavage of cytoskeletal proteins that lead to depolymerization of the cytoskeleton surrounding the inclusions. In this way the microbe uses the lack of ability of the infected host cells to maintain their cytoskeletal structure, to expand the chlamydial inclusions in favor of their rapid replication [1, 13]. The microbe uses Golgi-derived lipids like sphingomyelin and cholesterol via the chlamydial proteases. Cleavage of golgin-84 leads to recruitment of Golgi fragmentation to acquire nutrients [1, 13].
