The Association of OASL and Type I Interferons in the Pathogenesis and Survival of Intracellular Replicating Bacterial Species

abstract: ...The type I IFN response quickly became associated with its role in the innate immune response to viral infection. The past few years have seen the significance of IFNs expand in breadth to include non-viral pathogens. Previous work has identified that following viral infection, type I IFN signaling induces the production of the 2-5-oligoadenylate synthetase (OAS) family, which include OAS1, OAS2, OAS3, and OAS-like (OASL) protein. OASL was identified to be strongly induced following viral infection through engaging the RNA sensor RIG-I and increasing signaling through this pathway to enhance the anti-viral type I IFN response. Surprisingly, infection with viral dsDNA revealed an IFN inhibitory role and therefore pro-viral function of OASL through the inhibition of the cGAS cytosolic DNA sensing mechanism. Intracellular bacteria are able to activate the cytosolic DNA sensing pathway, however the role of OASL during bacterial infection is largely unknown. Vacuolar pathogenic microbes such as mycobacteria induce OASL early post infection, where it functions in a prosurvival fashion by inhibiting autophagic mechanisms and antimicrobial peptide expression. This suggests an underestimated role of OASL in the innate immune response to infection with a variety of pathogens and points to OASL-associated modulation of the type I IFN response. OASL may therefore play a critical role in defining the outcome of infection. We provide a brief update on the recent developments of the OAS family of proteins in response to DNA and RNA virus infections, as well as discuss evidence of Oasl expression in response to a number of cytosolic and vacuolar replicating bacterial pathogens.

...Front Cell Infect Microbiol Front Cell Infect Microbiol Front. Cell. Infect. Microbiol. Frontiers in Cellular and Infection Microbiology 2235-2988 Frontiers Media S.A. 28580319 5437694 10.3389/fcimb.2017.00196 Microbiology Mini Review The Association of OASL and Type I Interferons in the Pathogenesis and Survival of Intracellular Replicating Bacterial Species Leisching Gina * Wiid Ian Baker Bienyameen SAMRC Centre for TB Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis

... in the innate immune response to viral infection. The past few years have seen the significance of IFNs expand in breadth to include non-viral pathogens. Previous work has identified that following viral infection, type I IFN signaling induces the production of the 2-5-oligoadenylate synthetase (OAS) family, which include OAS1, OAS2, OAS3, and OAS-like (OASL) protein. OASL was identified to be strongly induced following viral infection through engaging the RNA sensor RIG-I and increasing signaling through this pathway to enhance the anti-viral type I IFN response. Surprisingly, infection with viral dsDNA revealed an IFN inhibitory role and therefore pro-viral function of OASL through the inhibition of the cGAS cytosolic DNA sensing mechanism. Intracellular bacteria are able to activate the cytosolic DNA sensing pathway, however the role of OASL during bacterial infection is largely unknown. Vacuolar pathogenic microbes such as mycobacteria induce OASL early post infection, where it functions in a prosurvival fashion by inhibiting autophagic mechanisms and antimicrobial peptide expression. This suggests an underestimated role of OASL in the innate immune response to infection with a variety of pathogens and points to OASL-associated modulation of the type I IFN response. OASL may therefore play a critical role in defining the outcome of infection. We provide a brief update on the recent developments of the OAS family of proteins in response to DNA and RNA virus infections, as well as discuss evidence of Oasl expression in response to a number of cytosolic and vacuolar replicating bacterial pathogens. OASL OAS cGAS STING Type I IFN mycobacteria pathogenesis Department of Science and Technology, Republic of South Africa 10.13039/501100001342 South African Medical Research Council 10.13039/501100001322 Introduction The 2-5-oligoadenylate synthetases (OAS) were the first interferon (IFN)-induced antiviral proteins described that are regulated by both type I and II IFNs (Zhou et al., 1997 ; Eskildsen et al., 2003 ). Originally, type I IFNs were discovered as mediators of the host response to viral infection, however it is now well-know that type I IFN induction is central to the genetic response of both viral and bacterial pathogens (Uematsu and Akira, 2006 ). The OAS family of proteins consists of OAS1, OAS2, OAS3, and OAS-like (OASL) protein. The OAS proteins exhibit anti-viral functions through indirectly impeding the translation of viral nucleic acids through the activation of RNase L. OASL on the other hand, is related to the OAS family by a N-terminal OAS-like domain but lacks synthetase activity. The lack of enzymatic activity is by no means an indication of a lack of function, as recently an anti-viral role was ascribed that is underpinned by the ability of OASL to enhance of IFN I signaling (Melchjorsen et al., 2009 ; Zhu et al., 2014 , 2015 ; Choi et al., 2015 ). On the heels of this discovery, it was observed that this antiviral function is specific to

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Gene: OASL - 2'-5'-oligoadenylate synthetase-like - (NCBI)

Protein : 1wh3

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