Impact of caspase-1/11, -3, -7, or IL-1β/IL-18 deficiency on rabies virus-induced macrophage cell death and onset of disease

Rabies virus is a highly neurovirulent RNA virus, which causes about 59000 deaths in humans each year. Previously, we described macrophage cytotoxicity upon infection with rabies virus. Here we examined the type of cell death and the role of specific caspases in cell death and disease development upon infection with two laboratory strains of rabies virus: Challenge Virus Standard strain-11 (CVS-11) is highly neurotropic and lethal for mice, while the attenuated Evelyn-Rotnycki-Abelseth (ERA) strain has a broader cell tropism, is non-lethal and has been used as an oral vaccine for animals. Infection of Mf4/4 macrophages with both strains led to caspase-1 activation and IL-1β and IL-18 production, as well as activation of caspases-3, -7, -8, and -9. Moreover, absence of caspase-3, but not of caspase-1 and -11 or -7, partially inhibited virus-induced cell death of bone marrow-derived macrophages. Intranasal inoculation with CVS-11 of mice deficient for either caspase-1 and -11 or -7 or both IL-1β and IL-18 led to general brain infection and lethal disease similar to wild-type mice. Deficiency of caspase-3, on the other hand, significantly delayed the onset of disease, but did not prevent final lethal outcome. Interestingly, deficiency of caspase-1/11, the key executioner of pyroptosis, aggravated disease severity caused by ERA virus, whereas wild-type mice or mice deficient for either caspase-3, -7, or both IL-1β and IL-18 presented the typical mild symptoms associated with ERA virus. In conclusion, rabies virus infection of macrophages induces caspase-1- and caspase-3-dependent cell death. In vivo caspase-1/11 and caspase-3 differently affect disease development in response to infection with the attenuated ERA strain or the virulent CVS-11 strain, respectively. Inflammatory caspases seem to control attenuated rabies virus infection, while caspase-3 aggravates virulent rabies virus infection

Hepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017

Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205254/Between 1 June 2016 and 31 May 2017, 17 European Union (EU) and European Economic Area countries reported 4,096 cases associated with a multi-country hepatitis A (HA) outbreak. Molecular analysis identified three co-circulating hepatitis A virus (HAV) strains of genotype IA: VRD_521_2016, V16-25801 and RIVM-HAV16-090. We categorised cases as confirmed, probable or possible, according to the EU outbreak case definitions. Confirmed cases were infected with one of the three outbreak strains. We investigated case characteristics and strain-specific risk factors for transmission. A total of 1,400 (34%) cases were confirmed; VRD_521_2016 and RIVM-HAV16-090 accounted for 92% of these. Among confirmed cases with available epidemiological data, 92% (361/393) were unvaccinated, 43% (83/195) travelled to Spain during the incubation period and 84% (565/676) identified as men who have sex with men (MSM). Results depict an HA outbreak of multiple HAV strains, within a cross-European population, that was particularly driven by transmission between non-immune MSM engaging in high-risk sexual behaviour. The most effective preventive measure to curb this outbreak is HAV vaccination of MSM, supplemented by primary prevention campaigns that target the MSM population and promote protective sexual behaviour.info:eu-repo/semantics/publishedVersio

Comparative Tick-Borne Encephalitis (Virus) Surveillance in Belgium 2009-2015: Experiences with Diagnostic Tests, Sentinel Species and Surveillance Designs

&lt;p&gt;When it is not overtly affecting human beings, the Tick-Borne Encephalitis Flavivirus (TBEV) remains mostly unnoticed during its enzootic cycles within vectors and unaffected animal species. Until recently, Belgium was &amp;ldquo;presumed&amp;rdquo; free of this important neuro-pathogenic virus without any scientific substantiation. Nonetheless, Belgium is clearly at risk of Tick-Borne Encephalitis (TBE) emergence&lt;/p&gt; &lt;p&gt;and incursions from endemic zones in the neighboring countries. This comparative review paper describes 5 Belgian veterinary serological studies with enzyme-linked immunosorbent assays and seroneutralisation tests (ELISA/SNT), in which several surveillance schemes were used (active/passive, risk-/laboratory-/range-based) in classic TBE sentinel species (dogs, cattle, roe deer, wild boar). Additionally, passive syndromic surveillance in two medical laboratories resulted in inconclusive medical data. Details are given on the scientists&amp;rsquo; experiences with available first/second line diagnostic tests and with the different surveillance methods/survey designs. Each of the veterinary studies clearly demonstrated the presence of TBEV-specific antibodies in Belgian sentinels, sometimes even at high seroneutralisation (SNT) titers, while the medical data remain so far inconclusive, despite positive&lt;/p&gt; &lt;p&gt;reactions of some patients in some TBEV-tests. These results have substantiated our suspicion of TBEV-presence in Belgium from 2010 onwards and have allowed sentinel comparisons based on &amp;ldquo;suitability criteria&amp;rdquo;. Furthermore, the studies have highlighted the need for further veterinary validation of commercial ELISA tests in comparison to the gold standard SNT.&lt;/p&gt;</p