ABSTRACT
Alphaviruses are mosquito borne RNA viruses that are a reemerging public health threat. Alphaviruses have a broad host range, and can cause diverse disease outcomes like arthritis, and encephalitis. The host ubiquitin proteasome system (UPS) plays critical roles in regulating cellular processes to control the infections with various viruses, including alphaviruses. Previous studies suggest alphaviruses hijack UPS for virus infection, but the molecular mechanisms remain poorly characterized. In addition, whether certain E3 ubiquitin ligases or deubiquitinases act as alphavirus restriction factors remains poorly understood. Here, we employed a cDNA expression screen to identify E3 ubiquitin ligase TRIM32 as a novel intrinsic restriction factor against alphavirus infection, including VEEV-TC83, SINV, and ONNV. Ectopic expression of TRIM32 reduces alphavirus infection, whereas depletion of TRIM32 with CRISPR-Cas9 increases infection. We demonstrate that TRIM32 inhibits alphaviruses through a mechanism that is independent of the TRIM32-STING-IFN axis. Combining reverse genetics and biochemical assays, we found that TRIM32 interferes with genome translation after membrane fusion, prior to replication of the incoming viral genome. Furthermore, our data indicate that the monoubiquitination of TRIM32 is important for its antiviral activity. Notably, we also show two TRIM32 pathogenic mutants R394H and D487N, related to Limb-girdle muscular dystrophy (LGMD), have a loss of antiviral activity against VEEV-TC83. Collectively, these results reveal that TRIM32 acts as a novel intrinsic restriction factor suppressing alphavirus infection and provides insights into the interaction between alphaviruses and the host UPS.
ABSTRACT
Transgenic technology is a crucial tool for gene functional analysis and targeted genetic modification in the para rubber tree (Hevea brasiliensis). However, low efficiency of plant regeneration via somatic embryogenesis remains a bottleneck of successful genetic transformation in H. brasiliensis. Enhancing expression of GROWTH-REGULATING FACTOR 4 (GRF4)-GRF-INTERACTING FACTOR 1 (GIF1) has been reported to significantly improve shoot and embryo regeneration in multiple crops. Here, we identified endogenous HbGRF4 and HbGIF1 from the rubber clone Reyan7-33-97, the expressions of which dramatically increased along with somatic embryo (SE) production. Intriguingly, overexpression of HbGRF4 or HbGRF4-HbGIF1 markedly enhanced the efficiency of embryogenesis in two H. brasiliensis callus lines with contrasting rates of SE production. Transcriptional profiling revealed that the genes involved in jasmonic acid response were up-regulated, whereas those in ethylene biosynthesis and response as well as the S-adenosylmethionine-dependent methyltransferase activity were down-regulated in HbGRF4- and HbGRF4-HbGIF1-overexpressing H. brasiliensis embryos. These findings open up a new avenue for improving SE production in rubber tree, and help to unravel the underlying mechanisms of HbGRF4-enhanced somatic embryogenesis.
Subject(s)
Hevea , Hevea/genetics , Rubber/metabolism , Latex , Gene Expression Regulation, PlantABSTRACT
Nocardiosis is a rare but severe pyogenic or granulomatous disease and caused by Nocardia that mainly infects immunocompromised patients. We report here a case of an immunocompetent 24-year-old male student with community-acquired pneumonia with asymptomatic disseminated cerebral abscess by Brasiliensis nocardiosis. The patient was fully recovered after receiving optimized antimicrobial therapy without relapse. This case suggests the health professionals such as the physicians of pulmonary, infection, neurology department and et al should always think about unusual cause of community acquired pneumonia, even in immunocompetent patients and when having pulmonary nocardiosis we should do a radiological neurological work up, even with the absence of neurological finding or symptom.
Subject(s)
Nocardia Infections/diagnosis , Nocardia/isolation & purification , Pneumonia, Bacterial/diagnosis , Anti-Infective Agents/therapeutic use , Brain/pathology , Brain Abscess/diagnostic imaging , Brain Abscess/pathology , Community-Acquired Infections/diagnosis , Humans , Immunocompetence , Lung/diagnostic imaging , Male , Nocardia Infections/drug therapy , Pneumonia, Bacterial/drug therapy , Radiography , Young AdultABSTRACT
Abstract: Bayesian Schaefer model was applied to assess the stock of Illex argentinus in the Southwest Atlantic Ocean, with the risk of alternative management strategies for the squid analyzed. Under the scenarios of normal and uniform prior assumptions, the estimated model parameters and reference points were similar, and higher than the values under the scenario of logarithmic normal prior assumption. Under the three proposed scenarios, the fishing mortalities and the total catches in 2001-2010 were lower than the reference point F0.1 and the maximum sustainable yield (MSY), indicating that the I. argentinus was in an expected sustainable exploited level but not in over-fishing and over-fished. The results of decision analysis indicated that at the same harvest rate, the stock of the I. argentinus under the scenario of logarithmic normal prior assumption in 2025 would be the lowest, and the probability of collapse would be the highest. Under the three scenarios, the harvest rate in 2025 would be all 0.6 if the catch was the maximum. However, if the harvest rate was set to 0.6, the stock of the I. argentinus after 2025 would have definite risk, and thus, the harvest rate 0.4 and the catch 550000 t appeared to be the best management regulation or the baseline case.