The early events in Junín virus (JUNV) infection are not thoroughly understood. We have previously shown that JUNV enter cells by clathrin-mediated endocytosis. In this report we examine the role of microfilaments and microtubules during early virus infection. Inhibitory effects of drugs affecting main cytoskeletal components on JUNV entry into Vero cells were analyzed. Drugs that disrupted microfilaments or stabilized microtubules inhibited early steps of virus entry. In contrast, drugs that stabilized microfilaments or depolymerized microtubules were not able to block virus entry very efficiently. Furthermore, real time PCR was performed to detect viral entry and we found more than 10-fold less RNA when microfilaments were depolymerized while a 100-fold diminution was seen when microtubules were stabilized. Taken together our results demonstrate that JUNV relies on an intact actin network during early infection in Vero cells while a dynamic microtubule network is also needed. This represents an important contribution to the characterization of arenavirus multiplication cycle.
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http://dx.doi.org/10.1016/j.virusres.2008.08.004 | DOI Listing |
JACS Au
January 2025
Department of Physics, Freie Universität Berlin, Arnimallee 14, Berlin 14195, Germany.
Interactions of polyelectrolytes (PEs) with proteins play a crucial role in numerous biological processes, such as the internalization of virus particles into host cells. Although docking, machine learning methods, and molecular dynamics (MD) simulations are utilized to estimate binding poses and binding free energies of small-molecule drugs to proteins, quantitative prediction of the binding thermodynamics of PE-based drugs presents a significant obstacle in computer-aided drug design. This is due to the sluggish dynamics of PEs caused by their size and strong charge-charge correlations.
View Article and Find Full Text PDFJACS Au
January 2025
Department of Biomedical Engineering, University of Virginia, Box 800759, Charlottesville, Virginia 22908, United States.
Cell entry by enveloped viruses involves a set of multistep, multivalent interactions between viral and host proteins as well as manipulation of nanoscale membrane mechanics by these interacting partners. A mechanistic understanding of these events has been challenging due to the complex nature of the interactions and the event-to-event heterogeneity involved. Single-virus microscopy has emerged as a powerful technique to probe viral binding and fusion kinetics.
View Article and Find Full Text PDFSci Rep
January 2025
Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Dengue is a mosquito-borne disease caused by dengue virus (DENV) infection, which remains a major public health concern worldwide owing to the lack of specific treatments or antiviral drugs available. This study investigated the potential repurposing of domperidone, an antiemetic and gastrokinetic agent, to control DENV infection. Domperidone was identified by pharmacophore-based virtual screening as a small molecule that can bind to both the viral envelope (E) and the nonstructural protein 1 (NS1) of DENV.
View Article and Find Full Text PDFVirology
January 2025
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. Electronic address:
Feline infectious peritonitis (FIP), a fatal disease in cats caused by feline infectious peritonitis virus (FIPV), has limited treatment options and lacks effective vaccines. Cepharanthine (CEP), a natural isoquinoline alkaloid, possesses many medicinal properties, including antiviral activities. However, the role of CEP in management of FIPV infection remains poorly understood.
View Article and Find Full Text PDFMol Biol Cell
January 2025
Institute for Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.
Tetraspanins (Tspans) are transmembrane proteins that coordinate life cycle steps of viruses from distinct families. Here, we identify the human Tspan10 and Tspan15, both members of the TspanC8 subfamily, as replication factors for alphavirus Venezuelan equine encephalitis virus (VEEV) in astrocytoma cells. Pharmacological inhibition and siRNA-mediated silencing of TspanC8 interactor a disintegrin and metalloproteinase 10 (ADAM10) reduced VEEV infection.
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