Viruses, Vol. 12, Pages 370: RNA-Binding Domains of Heterologous Viral Proteins Substituted for Basic Residues in the RSV Gag NC Domain Restore Specific Packaging of Genomic RNA

Viruses, Vol. 12, Pages 370: RNA-Binding Domains of Heterologous Viral Proteins Substituted for Basic Residues in the RSV Gag NC Domain Restore Specific Packaging of Genomic RNA Viruses doi: 10.3390/v12040370 Authors: Breanna L. Rice Timothy L. Lochmann Leslie J. Parent The Rous sarcoma virus Gag polyprotein transiently traffics through the nucleus, which is required for efficient incorporation of the viral genomic RNA (gRNA) into virus particles. Packaging of gRNA is mediated by two zinc knuckles and basic residues located in the nucleocapsid (NC) domain in Gag. To further examine the role of basic residues located downstream of the zinc knuckles in gRNA encapsidation, we used a gain-of-function approach. We replaced a basic residue cluster essential for gRNA packaging with heterologous basic residue motif (BR) with RNA-binding activity from either the HIV-1 Rev protein (Rev BR) or the HSV ICP27 protein (ICP27 BR). Compared to wild-type Gag, the mutant ICP27 BR and Rev BR Gag proteins were much more strongly localized to the nucleus and released significantly lower levels of virus particles. Surprisingly, both the ICP27 BR and Rev BR mutants packaged normal levels of gRNA per virus particle when examined in the context of a proviral vector, yet both mutants were noninfectious. These results support the hypothesis that basic residues located in the C-terminal region of NC are required for selective gRNA packaging, potentially by binding non-specifically to RNA via...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research

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Publication date: Available online 24 May 2020Source: Antiviral ResearchAuthor(s): Jungang Chen, Haiwei Zhang, Xulin Chen
Source: Antiviral Therapy - Category: Virology Source Type: research
ConclusionThe SARS-CoV-2 pandemic caused a significant reduction in healthcare (surgery, radiotherapy, chemotherapy) for malignancies of the musculoskeletal system. Delaying or stopping these treatments is life-threatening or can cause severe morbidity, pain, and loss of function. Although the coronavirus disease causes severe medical complications, serious collateral damage including death due to delayed or untreated sarcomas should be avoided.
Source: International Orthopaedics - Category: Orthopaedics Source Type: research
Ewing ’s sarcoma usually presents in paediatric patients with its primary location being bone tissue. Nevertheless, we present such an adult case which arises from the small intestine. We registered thirty one ...
Source: BMC Surgery - Category: Surgery Authors: Tags: Case report Source Type: research
This study included 3435 PTCs, 1985 of which were PTMCs. We performed targeted next-generation sequencing for 221 PTCs and integrated these data with the data including The Cancer Genome Atlas (TCGA) project. The frequency of v-raf murine sarcoma viral oncogene homolog B (BRAF)V600E mutation was higher in PTMCs >0.5 cm than that in very small PTMCs (≤0.5 cm) and decreased again in PTCs >2 cm. Among PTMCs, the prevalence of mutations in rat sarcoma (RAS) and telomerase reverse transcriptase (TERT) promoter was not significantly different according to their size, but lower than in large PTCs. There was n...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
AbstractBackgroundTo elucidate the clinicopathological features, hospital-based care volume and prognoses associated with primary retroperitoneal sarcoma (PRS).MethodsClinical data on PRS cases, diagnosed from 2008 to 2009 (cohort A) and from 2012 to 2015 (cohort B), were obtained from the national hospital-based cancer registry in Japan. Since data on survival, 5  years after PRS diagnosis, were available only for cohort A, patient prognoses were analyzed in this group alone.ResultsThe numbers of participating hospitals were 154 in cohort A and 537 in cohort B. In total, 380 and 2011 patients with PRS were identified...
Source: International Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. There are two subtypes, fusion gene-positive RMS (FP-RMS) and fusion gene-negative RMS (FN-RMS), depending on the presence of a fusion g...
Source: Cancer Cell International - Category: Cancer & Oncology Authors: Tags: Primary research Source Type: research
In this study, we aimed to investigate the role of HCG in vascular smooth muscle cells. HCG18 was over-expressed by adenovirus transfection and knocked down in vascular smooth muscle cells by shRNA. Cell proliferation was detected by CCK-8 assays. Flow cytometry was employed to test the impacts of HCG18 on vascular smooth muscle apoptotic cells. The expression of associated genes in protein and mRNA levels was detected by western blotting, immunofluorescence and qRT-PCR. The interactions between HCG18 and fused in sarcoma (FUS) were confirmed by RNA EMSA and RIP assays. The expression of serum HCG18 was decreased in hypert...
Source: Human Cell - Category: Cytology Source Type: research
l Sumit Sahni Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid tumors in the world. Currently, there are no approved targeted therapies for PDAC. Mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) are known to be a major driver of PDAC progression, but it was considered an undruggable target until recently. Moreover, PDAC also suffers from drug delivery issues due to the highly fibrotic tumor microenvironment. In this perspective, we provide an overview of recent developments in targeting mutant KRAS and strategies to overcome drug delivery issues (e.g., nanoparticle delivery). Over...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Perspective Source Type: research
We report a rare case of primary spinal intramedullary Ewing-like sarcoma harboringCIC-DUX4 translocation. A 23-year-old man presented with weakness in the extremities. Magnetic resonance imaging revealed a large intramedullary tumor spanning C3 –C5 with heterogeneous enhancement following gadolinium administration. Histologically, most of the tumor displayed dense myeloid proliferation composed of medium- to slightly small-sized primitive cells. Postoperatively, he received local adjuvant radiation therapy without tumor progression for 1 0 months. Target RNA sequencing analysis revealed theCIC-DUX4 fusion gene....
Source: Brain Tumor Pathology - Category: Neurology Source Type: research
Conditions:   Radiation Induced Neoplasms;   Radiation-Induced Cancer;   Recurrent Sarcoma;   Recurrent Soft Tissue Sarcoma Interventions:   Radiation: Hypofractionated radiotherapy;   Other: Hyperthermia Sponsor:   Maria Sklodowska-Curie Institute - Oncology Center Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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