Virucidal activity of Formulation I of the World Health Organization's alcohol-based handrubs: impact of changes in key ingredient levels and test parameters.

BACKGROUND: A recently modified World Health Organization (WHO) Formulation I was examined as 80% and 97% solutions against poliovirus type 1, adenovirus type 5 and murine norovirus according to the new European Norm prEN 14476:2011. In a previous study the unmodified WHO Formulation I had failed to demonstrate a sufficient activity against poliovirus type 1 according to the European Norm EN 14476-2007 whereas a sufficient activity was seen with adeno- and norovirus. FINDINGS: The modified WHO Formulation I demonstrated a virucidal activity against all 3 test viruses of the European Norm prEN 14476:2011 under clean conditions. This was achieved as 80% solution against adeno- and norovirus within 30 seconds and as 97% solution against poliovirus within 60 seconds. Testing the unmodified WHO Formulation I against poliovirus type 1 in the 97% assay of the European Norm prEN 14476:2011 an identical activity could be demonstrated. When comparing the 80% and the 97% assay of the European Norm prEN 14476:2011 the modified WHO Formulation I as 80% solution was active against adenovirus type 5 within 30 seconds whereas the 97% solution failed within 2 minutes exposure time. CONCLUSIONS: The technical possibility in the new European Norm prEN 14476:2011 allows testing a ready-to-use disinfectant as 97% solution and is responsible for the new virucidal claim of the modified WHO Formulation I. In contrast to the improvements with poliovirus type 1 the activity against adenovirus type 5 decreased when increasing the test concentration from 80% to 97%.

Inactivation of murine norovirus by chemical biocides on stainless steel.

BACKGROUND: Human norovirus (NoV) causes more than 80% of nonbacterial gastroenteritis in Europe and the United States. NoV transmission via contaminated surfaces may be significant for the spread of viruses. Therefore, measures for prevention and control, such as surface disinfection, are necessary to interrupt the dissemination of human NoV. Murine norovirus (MNV) as a surrogate for human NoV was used to study the efficacy of active ingredients of chemical disinfectants for virus inactivation on inanimate surfaces. METHODS: The inactivating properties of different chemical biocides were tested in a quantitative carrier test with stainless steel discs without mechanical action. Vacuum-dried MNV was exposed to different concentrations of alcohols, peracetic acid (PAA) or glutaraldehyde (GDA) for 5 minutes exposure time. Detection of residual virus was determined by endpoint-titration on RAW 264.7 cells. RESULTS: PAA [1000 ppm], GDA [2500 ppm], ethanol [50% (v/v)] and 1-propanol [30% (v/v)] were able to inactivate MNV under clean conditions (0.03% BSA) on the carriers by > or = 4 log10 within 5 minutes exposure time, whereas 2-propanol showed a reduced effectiveness even at 60% (v/v). Furthermore, there were no significant differences in virus reduction whatever interfering substances were used. When testing with ethanol, 1- and 2-propanol, results under clean conditions were nearly the same as in the presence of dirty conditions (0.3% BSA plus 0.3% erythrocytes). CONCLUSION: Products based upon PAA, GDA, ethanol and 1-propanol should be used for NoV inactivation on inanimate surfaces. Our data provide valuable information for the development of strategies to control NoV transmission via surfaces.

Hepatitis A virus protein 2B suppresses beta interferon (IFN) gene transcription by interfering with IFN regulatory factor 3 activation.

Hepatitis A virus (HAV) antagonizes the innate immune response by inhibition of retinoic acid-inducible gene I-mediated and melanoma differentiation-associated gene 5-mediated beta interferon (IFN-beta) gene expression. This study showed that this is due to an interaction of HAV with mitochondrial antiviral signalling protein (MAVS)-dependent signalling, in which the viral non-structural protein 2B and the protein intermediate 3ABC recently suggested in this context seem to be involved, cooperatively affecting the activities of MAVS and the kinases TANK-binding kinase 1 (TBK1) and the inhibitor of NF-kappaB kinase epsilon (IKKepsilon). In consequence, interferon regulatory factor 3 (IRF-3) is not activated. As IRF-3 is necessary for IFN-beta transcription, inhibition of this factor results in efficient suppression of IFN-beta synthesis. This ability might be of vital importance for HAV, which is an exceptionally slow growing virus sensitive to IFN-beta, as it allows the virus to establish infection and maintain virus replication for a longer period of time.

Hepatitis A virus inhibits cellular antiviral defense mechanisms induced by double-stranded RNA.

The consequences of a hepatitis A virus (HAV) infection on cell-based antiviral responses and the interactions between virus and host cells resulting in persistent infections are poorly understood. In this report, we show that HAV does inhibit double-stranded (dsRNA)-induced beta interferon (IFN-beta) gene expression by influencing the IFN-beta enhanceosome, as well as dsRNA-induced apoptosis, which suggests that both effects may be connected by shared viral and/or cellular factors. This ability of HAV, which preserves the sites of virus production for a longer time, may allow the virus to establish an infection and may be the presupposition for setting up persistent infections. Our results suggest that the inhibitory effect of HAV on the cellular defense mechanisms might not be sufficient to completely prevent the antiviral reactions, which may be induced by accumulating viral dsRNA, at a later stage of infection. However, HAV seems to counteract this situation by downregulation of viral replication and in the following production of viral dsRNA. This ability of noncytopathogenic HAV acts dominantly on cytopathogenic HAV in trans. The downregulation might ensure the moderate replication which seems necessary for inhibition of the antiviral mechanisms by HAV and therefore for the persistent state of the HAV infection.