(BoAHV-1) infection is common in cattle worldwide. However, information on the spread of BoAHV-1-circulating strains in Italy remains limited. In this study, we investigated an outbreak characterized ...by severe respiratory symptoms in a cattle herd (
= 30) located in Central Italy. BoAHV-1 was isolated from three cattle in a cell culture, which confirmed viral infection. Next, we characterized one (16453/07 TN) of the three isolates of BoAHV-1 using whole-genome sequencing. BLASTn and phylogenetic analysis revealed a nucleotide identity >99% with all BoAHV-1 strains belonging to subtype 1.1, highlighting the genetic stability of the virus. This study reports the first full genomic characterization of a BoAHV-1 isolate in Italy, enriching our understanding of the genetic characteristics of the circulating BoAHV-1 strain in Italy.
Seronegative latent carriers (SNLCs) are animals that carry the virus without detectable antibodies and pose a risk for disease transmission and diagnostic challenges, suggesting the importance of ...consideration of marker vaccines in managing them. Therefore, in this study, we evaluated two modified live infectious bovine rhinotracheitis (IBR) marker vaccines (single and double deletions) for their ability to generate SNLC calves. These vaccines were administered to four groups (n = 3 in each group) of three-month-old calves in the presence or absence of passive immunity. Three hundred days after the first vaccination and after confirming the IBR seronegativity of all animals, dexamethasone was administered intravenously for five consecutive days. Only animals immunized with the modified live IBR marker vaccine (single deletion) in the absence of passive immunity exhibited a more enduring immune response than those vaccinated in the presence of passive immunity. Moreover, the administration of a modified live IBR marker vaccine (double deletion) to calves with passive immunity generated SNLC. These findings underscore the potential of live IBR marker vaccine (double-deletions) to aid serological diagnostic tools and develop vaccination protocols in achieving the desired immune response, particularly in the context of latent carrier status, offering valuable insights into optimizing vaccination strategies for effective IBR control.
Three commercially available infectious bovine rhinotracheitis (IBR) live marker vaccines were evaluated for their ability to provide clinical protection to vaccinated calves against wild-type (wt) ...Bovine alphaherpesvirus-1 (BoHV-1) challenge and their possible effect on wt BoHV-1 latency reactivation following the challenge. On 35 post-vaccination days (PVDs), all animals were challenged with wt BoHV-1. Only the calves in the control group developed severe forms of IBR. The reactivation of latent BoHV-1 was induced by dexamethasone (DMS) treatment on 28 post-challenge days (PCDs). All animals showed IBR clinical signs on three post-DMS treatment days (PDTDs). On PVD 14, all vaccinated animals developed neutralizing antibodies (NAs), whereas in control animals, the NAs appeared post-challenge. The positivity for glycoprotein-B (gB) was detected using real-time polymerase chain reactions in all animals from PCDs 1 to 7. In contrast, the gB-positivity was observed in the immunized calves from PDTDs 3 to 10. Positive expression of gD and gE was observed in nasal swabs of all calves on PDTD 7. These findings suggested that the IBR marker vaccines evaluated in this study protected against wt BoHV-1-induced disease but not against wt BoHV-1-induced latency reactivation, indicating the necessity of developing new products to protect animals from wt BoHV-1-induced latency.
Bovine alphaherpesvirus-1 (BoAHV-1) infection is common in cattle worldwide. However, information on the spread of BoAHV-1-circulating strains in Italy remains limited. In this study, we investigated ...an outbreak characterized by severe respiratory symptoms in a cattle herd (n = 30) located in Central Italy. BoAHV-1 was isolated from three cattle in a cell culture, which confirmed viral infection. Next, we characterized one (16453/07 TN) of the three isolates of BoAHV-1 using whole-genome sequencing. BLASTn and phylogenetic analysis revealed a nucleotide identity >99% with all BoAHV-1 strains belonging to subtype 1.1, highlighting the genetic stability of the virus. This study reports the first full genomic characterization of a BoAHV-1 isolate in Italy, enriching our understanding of the genetic characteristics of the circulating BoAHV-1 strain in Italy.
KRIT1 is a disease gene responsible for Cerebral Cavernous Malformation (CCM), a major cerebrovascular disease of proven genetic origin affecting 0.3–0.5% of the population. Previously, we ...demonstrated that KRIT1 is involved in the control of intracellular redox homeostasis, suggesting that its loss-of-function may impair cell defense against oxidative stress. Here we found that KRIT1 loss induces a sustained redox-sensitive upregulation of the Nrf2 antioxidant defense pathway and its downstream target Glyoxalase 1 (Glo1), a pivotal stress-responsive defense enzyme involved in cellular protection against glycative and oxidative stress through the metabolism of methylglyoxal (MG). However, these effects were associated with a downregulation of major apoptosis-protective proteins, including MG-modified Hsp70 and Hsp27 proteins, and a consequent increased susceptibility to oxidative DNA damage and apoptosis. Overall, our data demonstrate that KRIT1 loss-of-function affects major mechanisms involved in adaptive responses to oxidative stress, leading to a sustained adaptive redox homeostasis that counteracts intrinsic oxidative stress but sensitizes cells to further oxidative challenges. These findings provide novel options for the development of targeted therapeutic strategies.
Cerebral Cavernous Malformation (CCM) is a major cerebrovascular disease with a prevalence of 0.3–0.5% in the general population and highly variable clinical expressivity. It may cause various ...symptoms at any age, including recurrent headaches, neurological deficits, seizures, and intracerebral hemorrhage, and has been associated with loss-of-function mutations in three CCM genes, CCM1 (KRIT1), CCM2 and CCM3. However, growing evidence in animal models demonstrates that loss of CCM genes is not sufficient to cause CCM disease, suggesting the contribution of additional triggers occurring locally in the neurovascular microenvironment, including stress factors. Indeed, we found that both cellular and animal models of CCM disease show an enhanced sensitivity to oxidative stress and inflammatory insults due to defects in mechanisms involved in cellular defense against these stressful conditions, including antioxidant responses and autophagy. Furthermore, we provide novel insights into the identification of risk factors and biomarkers associated with CCM disease progression and severity, including the accumulation of major glycation and oxidation products, which may serve as early objective predictors of disease outcome and provide better options for disease prevention and treatment.
Bovine alphaherpesvirus-1 (BoAHV-1) infection is common in cattle worldwide. However, information on the spread of BoAHV-1-circulating strains in Italy remains limited. In this study, we investigated ...an outbreak characterized by severe respiratory symptoms in a cattle herd (n = 30) located in Central Italy. BoAHV-1 was isolated from three cattle in a cell culture, which confirmed viral infection. Next, we characterized one (16453/07 TN) of the three isolates of BoAHV-1 using whole-genome sequencing. BLASTn and phylogenetic analysis revealed a nucleotide identity >99% with all BoAHV-1 strains belonging to subtype 1.1, highlighting the genetic stability of the virus. This study reports the first full genomic characterization of a BoAHV-1 isolate in Italy, enriching our understanding of the genetic characteristics of the circulating BoAHV-1 strain in Italy.
The present study aims to investigate the choroidal morphology and microvascular structure in eyes of patients with idiopathic normal pressure hydrocephalus (iNPH) compared with the eyes of healthy ...age-matched individuals, and to assess the choroidal structure in eyes of iNPH patients before and after shunt surgery using Optical Coherence Tomography (OCT). The primary objective was to assess the choroidal morphology in eyes of iNPH patients before and after ventriculo-peritoneal (VP) surgery compared to age and sex-matched healthy individuals. The secondary objective was to compare the choroidal morphology of iNPH patients before and after a mean of 56 days from shunt surgery. Eighteen consecutive patients diagnosed with iNPH and 18 healthy controls were prospectively recruited between November 2021 and October 2022. Spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) was conducted before and within 4 months after shunt surgery. Images were binarized using the ImageJ software, and the choroidal vascular index (CVI) was calculated. Sub-foveal choroidal thickness (SFCT), total choroidal area (TCA), luminal choroidal area (LCA), and stromal choroidal area (SCA) were significantly increased in iNPH patients before surgery compared to the control group (p < 0.05). SFCT, TCA, and SCA were significantly increased in iNPH patients after surgery compared to the control group (p < 0.05). There were no differences in the CVI between iNPH patients and controls. No statistical differences in the choroidal structure were observed before and after VP shunt surgery (p > 0.05). In conclusion, the choroid was thicker in iNPH patients before and after VP shunt compared to age-matched healthy individuals. However, there were no difference in the choroidal microstructure in the eyes of iNPH patients before and after a mean of 3 months from VP shunt surgery.
