The Journal of infectious diseases
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Histone deacetylases (HDACs) control gene expression by deacetylating histones and nonhistone proteins. HDAC inhibitors (HDACi) are powerful anticancer drugs that exert anti-inflammatory and immunomodulatory activities. We recently reported a proof-of-concept study demonstrating that HDACi increase susceptibility to bacterial infections in vivo. ⋯ In line with these findings, HDACi decrease the expression of phagocytic receptors and inhibit bacteria-induced production of reactive oxygen and nitrogen species by macrophages. Consistently, HDACi impair the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits and inducible nitric oxide synthase. These data indicate that HDACi have a strong impact on critical antimicrobial defense mechanisms in macrophages.
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Randomized Controlled Trial Multicenter Study Comparative Study
Safety and immunogenicity of LC16m8, an attenuated smallpox vaccine in vaccinia-naive adults.
LC16m8 is an attenuated cell culture-adapted Lister vaccinia smallpox vaccine missing the B5R protein and licensed for use in Japan. ⋯ LC16m8 generates neutralizing antibody titers to multiple poxviruses, including vaccinia, monkeypox, and variola major, and broad T-cell responses, indicating that LC16m8 may have efficacy in protecting individuals from smallpox. Clinical Trials Registration. NCT00103584.
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The 2008 Reston ebolavirus infection event in domestic pigs has triggered continuing epidemiologic investigations among Philippine health and veterinary agencies in collaboration with international filovirus experts. Prior to this, there were only 3 known and documented Reston ebolavirus outbreaks in nonhuman primates in the world, all traced back to a single geographic source in the Philippines in a monkey breeding/export facility. The first one in 1989 was the first-ever Ebola virus that emerged outside of Africa and was also the first known natural infection of Ebola virus in nonhuman primates. ⋯ The second outbreak was in 1992-93. The third episode in 1996 was the last known outbreak before Reston ebolavirus reemerged in pigs in 2008. The isolated outbreaks involving 2 animal species bring forth issues requiring further investigations, and highlight the significance of intersectoral collaboration to effectively address zoonoses prevention and control/response in the interest of minimizing public health risk.
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For Ebola virus (EBOV), 4 different species are known: Zaire, Sudan, Côte d'Ivoire, and Reston ebolavirus. The newly discovered Bundibugyo ebolavirus has been proposed as a 5th species. So far, no cross-neutralization among EBOV species has been described, aggravating progress toward cross-species protective vaccines. ⋯ New vectors were generated that contain EBOV viral protein 40 (VP40) or EBOV nucleoprotein (NP) as a second antigen expressed by the same rVSV vector that encodes the heterologous GP. After applying a 2-dose immunization approach, we observed an improved cross-protection rate, with 5 of 6 guinea pigs surviving the lethal ZEBOV challenge if vaccinated with rVSV-expressing SEBOV-GP and -VP40. Our data demonstrate that cross-protection between the EBOV species can be achieved, although EBOV-GP alone cannot induce the required immune response.
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We evaluated the susceptibility to Ebola and Marburg virus infection of mice that cannot respond to interferon (IFN)-α/β and IFN-γ because of deletion of the STAT-1 gene. A mouse-adapted Zaire ebolavirus (ZEBOV) caused rapidly lethal disease; wild-type ZEBOV and Sudan Ebolavirus and 4 different Marburg virus strains produced severe, but more slowly progressive illness; and Reston Ebolavirus caused mild disease that was late in onset. The virulence of each agent was mirrored by the pace and severity of pathologic changes in the liver and lymphoid tissues. A virus-like particle vaccine elicited strong antibody responses but did not protect against mouse-adapted ZEBOV challenge.