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Thrombotic Microangiopathy Associated with Systemic Adeno-Associated Virus Gene Transfer: Review of Reported Cases.
Hum Gene Ther
January 2025
BridgeBio Gene Therapy, Palo Alto, California, USA.
Complement-mediated thrombotic microangiopathy (TMA) in the form of atypical hemolytic uremic syndrome (aHUS) has emerged as an immune complication of systemic adeno-associated virus (AAV) gene transfer that was unforeseen based on nonclinical studies. Understanding this phenomenon in the clinical setting has been limited by incomplete data and a lack of uniform diagnostic and reporting criteria. While apparently rare based on available information, AAV-associated TMA/aHUS can pose a substantial risk to patients including one published fatality.
View Article and Find Full Text PDFVaccinia growth factor-dependent modulation of the mTORC1-CAD axis upon nutrient restriction.
J Virol
January 2025
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
The molecular mechanisms by which vaccinia virus (VACV), the prototypical member of the poxviridae family, reprograms host cell metabolism remain largely unexplored. Additionally, cells sense and respond to fluctuating nutrient availability, thereby modulating metabolic pathways to ensure cellular homeostasis. Understanding how VACV modulates metabolic pathways in response to nutrient signals is crucial for understanding viral replication mechanisms, with the potential for developing antiviral therapies.
View Article and Find Full Text PDFIsoleucine at position 137 of Hemagglutinin acts as a Mammalian adaptation marker of H9N2 Avian influenza virus.
Emerg Microbes Infect
January 2025
Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, Shenyang Agricultural University, Shenyang, People's Republic of China.
The H9N2 subtype of avian influenza virus (AIV) is widely distributed among poultry and wild birds and is also a threat to humans. During AIV active surveillance in Liaoning province from 2015 to 2016, we identified ten H9N2 strains exhibiting different lethality to chick embryos. Two representative strains, A/chicken/China/LN07/2016 (CKLN/07) and A/chicken/China/LN17/2016 (CKLN/17), with similar genomic background but different chick embryo lethality, were chosen to evaluate the molecular basis for this difference.
View Article and Find Full Text PDFTransferrin-binding domain inserted-adenovirus hexon engineering enables systemic immune evasion and intratumoral T-cell activation.
Theranostics
January 2025
Department of Pharmacology, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
Adenovirus-based therapies have encountered significant challenges due to host immunity, particularly from pre-existing antibodies. Many trials have struggled to evade antibody response; however, the efficiency of these efforts was limited by the diversity of antibody Fv-region recognizing multiple amino acid sequences. In this study, we developed an antibody-evading adenovirus vector by encoding a plasma-rich protein transferrin-binding domain.
View Article and Find Full Text PDFHeat acclimation defense against exertional heat stroke by improving the function of preoptic TRPV1 neurons.
Theranostics
January 2025
Department of Critical Care Medicine and Department of Anaesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China, 710032.
Record-breaking heatwaves caused by greenhouse effects lead to multiple hyperthermia disorders, the most serious of which is exertional heat stroke (EHS) with the mortality reaching 60 %. Repeat exercise with heat exposure, termed heat acclimation (HA), protects against EHS by fine-tuning feedback control of body temperature (Tb), the mechanism of which is opaque. This study aimed to explore the molecular and neural circuit mechanisms of the HA training against EHS.
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