Sensitivity of Human Mastadenovirus, the Causal Agent of Pharyngoconjunctival Fever, Epidemic Keratoconjunctivitis, and Hemorrhagic Cystitis in Immunocompromised Individuals, to Brincidofovir.

Human mastadenovirus (HAdV), a linear double-stranded DNA (dsDNA) virus, is the causal agent of several diseases, including pharyngoconjunctival fever, epidemic keratoconjunctivitis, and hemorrhagic cystitis, in immunocompromised individuals. There are more than 100 reported types of adenoviruses, but the pathogenicity of many HAdVs remains unknown. Brincidofovir (BCV) is a hexadecyloxypropyl lipid conjugate of cidofovir (CDV) that is active against dsDNA viruses. Clinical effectiveness of BCV against certain HAdV species has been reported; however, its activity against novel HAdV types remains unknown. We investigated the half-maximal inhibitory concentration (IC50) values of BCV for novel HAdV types and found that the epidemic keratoconjunctivitis-associated HAdV-D54 prevalent in the Asian region was the most susceptible. The mean overall IC50 value of BCV was lower than that of CDV, indicating that BCV is effective against HAdVs, including the novel types. IMPORTANCE We investigated the IC50 values of BCV for novel HAdV types and found that the epidemic keratoconjunctivitis-associated HAdV-D54 prevalent in the Asian region was the most susceptible. In addition, the mean overall IC50 value of BCV was lower than that of CDV, indicating that BCV is effective against HAdVs.

Evaluation of the Anti-Adenoviral Activity of ALTANT, an Ozonated Alcohol Disinfectant.

Seven human mastadenovirus (HAdV) species (A-G) are known with more than 100 reported types. HAdV is highly resistant to common hand sanitizers. Epidemic keratoconjunctivitis and pharyngoconjunctival fever are caused by HAdV, which can be explosively transmitted in a confined space, resulting in outbreaks, such as nosocomial infections. Given the absence of an antiviral agent against the HAdV infection, it is important to prevent the spread of the infection by using disinfectants. Ozone has already been well-known for its bactericidal and virucidal effects. ALTANT is an ozonated alcohol preparation developed by E-TECH Co., Ltd. (Kobe, Hyogo, Japan). In this study, we mixed ALTANT with different HAdV types at a ratio of 9:1 and determined HAdV viability after instantaneous reactions for varying periods (flash to 5 minutes) using the TCID50 assay. The assay results demonstrated that the HAdV viability decreased by 1/10 to 1/100 within 1 minute after the reaction; additionally, slight differences in the reactivity were observed among the HAdV types. HAdV viability decreased by a factor of > 4log10, and the virus was eliminated within 3 minutes. This study demonstrated the potent HAdV disinfection effect of ALTANT.

Evaluation of virucidal activity of three commercial disinfectants and formic acid using bovine enterovirus type 1 (ECBO virus), mammalian orthoreovirus type 1 and bovine adenovirus type 1.

A modified version of the test method of the Comité Européen de Normalisation (CEN) was developed using formic acid and three commercial disinfectants to evaluate virucidal activity against three non-enveloped viruses, bovine enterovirus type 1 (ECBO virus), mammalian orthoreovirus type 1 and bovine adenovirus type 1 (BAV 1). Determination of the effects of temperature was carried out at 20 and 10 degrees C. All tests with protein load used bovine serum albumin (BSA) and yeast extract. The investigations were performed in suspension tests and in carrier tests using poplar wood virus carriers. The carrier tests showed that ECBO virus could be inactivated at 20 degrees C with 1% formic acid within a 60 min reaction time. For disinfection of ECBO virus at 10 degrees C within 60 min, a 2% concentration of formic acid was necessary. Formic acid was ineffective against reovirus and bovine adenovirus and cannot be recommended as a reference disinfectant. Inactivation of ECBO virus and adenovirus type 1 using a disinfectant containing aldehydes and alcohols could be achieved, but only at room temperature. The disinfection of reovirus type 1 at room temperature with this product was possible without a protein load. This disinfectant exhibited disinfection ability at 10 degrees C at a concentration of more than 2% or with a longer exposure time. A disinfectant containing aldehydes was effective at room temperature but its effect was reduced in the presence of organic matter. Inactivation at 10 degrees C was found only against adenovirus. The fourth disinfectant, which contained peroxiacetic acid, inactivated all test viruses at a concentration of 0.5% within 15 min independent of temperature and protein load.

Evaluation of the efficacy of 2',3'-dideoxycytidine against adenovirus infection in a mouse pneumonia model.

The antiviral activity of 2',3'-dideoxycytidine (ddC) has been investigated in a mouse pneumonia model. Consolidation of lung, histopathological changes, DNA synthesis as well as levels of TNFalpha were assayed. In this in vivo model, the oral administration of ddC twice daily over 4 days, displayed an inhibitory effect. The drug significantly reduced histopathologic responses. Analysis indicated that under treatment pulmonary lesions were less severe than those of untreated controls. These data confirm the in vitro activity of ddC against adenovirus. Thus, ddC represents a potential therapeutic approach for inhibiting adenovirus infection and may offer promise as an anti-adenovirus agent for immunocompromised patients in whom serious adenovirus infection may prove fatal.

Mouse adenovirus type 1 replication in vitro is resistant to interferon.

The effects of mouse interferon (IFN)-alpha/beta and recombinant IFN-gamma on mouse adenovirus type 1 (MAV-1) replication were investigated in single-cycle infectious virus yield reduction assays on mouse L929 cells. Viral yields at 3 days postinfection indicated that wt MAV-1 and pmE314, an early region 3 null mutant, were relatively insensitive to both IFN-alpha/beta and IFN-gamma, whereas early region 1A (E1A) mutants pmE109 (null), dlE105 (conserved region 1 deletion, CR1 Delta), dlE102 (CR2 Delta), and dlE106 (CR3 Delta) were sensitive. MAV-1 E1A that was inducibly expressed in mouse fibroblast 37.1 cells rescued vesicular stomatitis virus from the antiviral effect of IFN-alpha/beta but not from the antiviral effect of IFN-gamma. Interferon-inducible gene expression was reduced in 37.1 cells as compared to the parental 3T6 cell line. Steady-state levels of IFN-inducible gene mRNAs were also reduced in 3T6 cells infected with the wild-type virus and pmE314 but not in cells infected with pmE109. These results suggest that the MAV-1 E1A gene product is capable of interfering with the signaling pathways of both types of IFN, although modulation of IFN-alpha/beta antiviral activity was more pronounced.