RESUMO
Stimulator of interferon genes (STING) plays important roles in the DNA-mediated innate immune responses. However, the regulatory mechanism of STING in terms of stabilization is not fully understood. Here, we identified the chaperone protein Hsp90s as novel STING interacting proteins. Treatment with an Hsp90 inhibitor 17-AAG and knockdown of Hsp90ß but not Hsp90α reduced STING at protein level, resulted in the suppression of IFN induction in response to stimulation with cGAMP, and infections with HSV-1 and Listeria monocytogenes. Collectively, our results suggest that the control of STING protein by Hsp90ß is a critical biological process in the DNA sensing pathways.
Assuntos
Proteínas de Choque Térmico HSP90/imunologia , Proteínas de Membrana/imunologia , Animais , DNA Viral/imunologia , Células HEK293 , Proteínas de Choque Térmico HSP90/metabolismo , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/imunologia , Humanos , Evasão da Resposta Imune/imunologia , Imunidade Inata , Listeria monocytogenes/genética , Listeria monocytogenes/imunologia , Proteínas de Membrana/metabolismo , Camundongos , Células RAW 264.7 , Transdução de Sinais , Proteínas Virais/metabolismoRESUMO
PURPOSE: The aim of this study was to test the antiviral effectivity of potassium peroxymonosulfate (RUBYSTA®, KYORIN) against five epidemic keratoconjunctivitis-related types of Human adenovirus D in vitro. METHODS: Five types of Human adenovirus D (8, 37, 53, 54 and 56) were incubated with 1% potassium peroxymonosulfate, 0.1% sodium hypochlorite (NaClO) or alcohol-based disinfectant for 30 s or 1 min. These solutions were subjected to measurements of viral titres by infection assays in A549 cells. At day 6 post-infection, both, supernatants and cells, were collected and the viral genome was assessed by real-time polymerase chain reaction analysis. RESULTS: Treatments with 1% potassium peroxymonosulfate led to significant reduction in all tested Human adenovirus D types comparable to disinfecting effects by 0.1% NaClO. Overall, potassium peroxymonosulfate demonstrated sufficient inactivation of the major epidemic keratoconjunctivitis-causing Human adenovirus D to be considered for disinfection and prevention purposes in ophthalmological clinics and hospitals. CONCLUSION: This study demonstrated that potassium peroxymonosulfate is a promising disinfectant for the prevention of epidemic keratoconjunctivitis nosocomial infections in ophthalmological clinics.
Assuntos
Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/efeitos dos fármacos , Desinfetantes/farmacologia , Ceratoconjuntivite/virologia , Oxidantes/farmacologia , Peróxidos/farmacologia , Células A549 , Infecção Hospitalar/prevenção & controle , Epidemias , Humanos , Replicação Viral/efeitos dos fármacosRESUMO
The interaction of viral nucleic acid with protein factors is a crucial process for initiating viral polymerase-mediated viral genome replication while activating pattern recognition receptor (PRR)-mediated innate immune responses. It has previously been reported that a hydrolysate of Ge-132, 3-(trihydroxygermyl) propanoic acid (THGP), shows a modulatory effect on microbial infections, inflammation, and immune responses. However, the detailed mechanism by which THGP can modify these processes during viral infections remained unknown. Here, we show that THGP can specifically downregulate type I interferon (IFN) production in response to stimulation with a cytosolic RNA sensor RIG-I ligand 5'-triphosphate RNA (3pRNA) but not double-stranded RNA, DNA, or lipopolysaccharide. Consistently, treatment with THGP resulted in the dose-dependent suppression of type I IFN induction upon infections with influenza virus (IAV) and vesicular stomatitis virus, which are known to be mainly sensed by RIG-I. Mechanistically, THGP directly binds to the 5'-triphosphate moiety of viral RNA and competes with RIG-I-mediated recognition. Furthermore, we found that THGP can directly counteract the replication of IAV but not EMCV (encephalitismyocarditis virus), by inhibiting the interaction of viral polymerase with RNA genome. Finally, IAV RNA levels were significantly reduced in the lung tissues of THGP-treated mice when compared with untreated mice. These results suggest a possible therapeutic implication of THGP and show direct antiviral action, together with the suppressive activity of innate inflammation.