Rabbit hemorrhagic disease virus (RHDV) and European brown hare syndrome virus (EBHSV) are caliciviruses that produce severe symptoms and are lethal to rabbits and hares. The folding of the capsid protein was studied by determination of the antigenic pattern of chimeric capsid proteins, composed of regions from RHDV and EBHSV capsid proteins. The anti-RHDV monoclonal antibody (MAb) E3, which is known to bind an external conformational epitope, recognized the RHDV C-terminal region. The anti-RHDV MAb A47, which binds a buried epitope, recognized the RHDV N-terminal region. Using a pGEX expression library, we more precisely mapped the MAb A47 epitope on a 31 residues length peptide, between residue 129 and 160 of the VP60, confirming its location in the N-terminal part of the protein. These results demonstrate that the C-terminal part of the protein is accessible to the exterior whereas the N-terminal domain of the protein constitutes the internal shell domain of the particle. With the aim of using virus-like particles (VLPs) of RHDV as epitope carriers or DNA transfer vectors, we produced in the baculovirus system three proteins, DeltaN1, DeltaN2 and DeltaN3, truncated at the N terminus. The DeltaN1 protein assembled into VLPs, demonstrating that the first 42 amino acid residues are not essential for capsid assembly. In contrast, DeltaN2, from which the first 75 residues were missing, was unable to form VLPs. The small particles obtained with the DeltaN3 protein lacking residues 31 to 93, located in the immunodominant region of the RHDV capsid protein, indicate that up to 62 amino acid residues can be eliminated without preventing assembly.
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http://dx.doi.org/10.1007/s00705-002-0825-3 | DOI Listing |
Front Bioinform
January 2025
Hakim's Lab, Department of Biology, School of STEM, Diné College, Tuba City, AZ, United States.
Introduction: Flaviviridae comprise a group of enveloped, positive-stranded RNA viruses that are mainly transmitted through either mosquitoes or tick bites and/or contaminated blood, blood products, or other body secretions. These viruses cause diseases ranging from mild to severe and are considered important human pathogens. MicroRNAs (miRNAs) are non-coding molecules involved in growth, development, cell proliferation, protein synthesis, apoptosis, and pathogenesis.
View Article and Find Full Text PDFVirol J
January 2025
Virology Laboratory, Faculty of Life Sciences and Biotechnology, South Asian University (SAU), New Delhi, 110068, India.
Maturation inhibitors (MIs) block HIV-1 maturation by preventing the cleavage of the capsid protein and spacer peptide 1 (CA-SP1). Bevirimat (BVM), a first-in-class MI, displayed sub-optimal efficacy in clinical trials due to presence of SP1:V7A polymorphism in the Gag protein.This polymorphism is inherently present in HIV-1 subtype C and conferred resistance to BVM.
View Article and Find Full Text PDFAnticancer Agents Med Chem
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Department of Gynecology, Lanzhou University Second Hospital Lanzhou University, Lanzhou, 730030, China.
Cervical cancer is a significant global health threat, ranking as the fourth most common malignancy among women and resulting in over 300,000 deaths annually. Although screening and vaccination initiatives have led to a decline in incidence rates, treatment options for advanced or recurrent cervical cancer remain inadequate, often proving ineffective and costly. In this context, adenoviral therapy has emerged as a promising strategy to enhance therapeutic outcomes.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Division of Infectious Diseases, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States of America.
Lenacapavir (LEN) is a highly potent, long-acting antiretroviral medication for treating people infected with muti-drug-resistant HIV-1 phenotypes. The inhibitor targets multifaceted functions of the viral capsid protein (CA) during HIV-1 replication. Previous studies have mainly focused on elucidating LEN's mode of action during viral ingress.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Ophthalmology, University of North Carolina, 130 Mason Farm Rd, Chapel Hill, NC 27517, USA.
Adeno-associated virus (AAV) inverted terminal repeats (ITRs) induce p53-dependent apoptosis in human embryonic stem cells (hESCs). To interrogate this phenomenon, a synthetic ITR (SynITR), harboring substitutions in putative p53 binding sites was generated and evaluated for vector production and gene delivery. Replication of SynITR flanked transgenic genome was similar compared to wild type (wt) ITR, with a modest increase in vector titers.
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