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Viruses, Vol. 14, Pages 1628: Inhibition of Venezuelan Equine Encephalitis Virus Using Small Interfering RNAs
In this study, novel vsiRNAs that targeted conserved regions in the nonstructural and structural genes of the VEEV genome were designed and evaluated for antiviral activity in mammalian cells in the context of VEEV infection. The data demonstrate that vsiRNAs were able to effectively decrease the infectious virus titer at earlier time points post infection in the context of the attenuated TC-83 strain and the virulent Trinidad Donkey strain, while the inhibition was overcome at later time points. Depletion of Argonaute 2 protein (Ago2), the catalytic component of the RISC complex, negated the inhibitory effect of the vsiRN...
Source: Viruses - July 26, 2022 Category: Virology Authors: Amrita Haikerwal Michael D. Barrera Nishank Bhalla Weidong Zhou Niloufar Boghdeh Carol Anderson Farhang Alem Aarthi Narayanan Tags: Article Source Type: research

Viruses, Vol. 13, Pages 288: Ubiquitin Ligase SMURF2 Interacts with Filovirus VP40 and Promotes Egress of VP40 VLPs
Ronald N. Harty Filoviruses Ebola (EBOV) and Marburg (MARV) are devastating high-priority pathogens capable of causing explosive outbreaks with high human mortality rates. The matrix proteins of EBOV and MARV, as well as eVP40 and mVP40, respectively, are the key viral proteins that drive virus assembly and egress and can bud independently from cells in the form of virus-like particles (VLPs). The matrix proteins utilize proline-rich Late (L) domain motifs (e.g., PPxY) to hijack specific host proteins that contain WW domains, such as the HECT family E3 ligases, to facilitate the last step of virus–cell separation. We...
Source: Viruses - February 12, 2021 Category: Virology Authors: Ariel Shepley-McTaggart Michael Patrick Schwoerer Cari A. Sagum Mark T. Bedford Chaitanya K. Jaladanki Hao Fan Joel Cassel Ronald N. Harty Tags: Article Source Type: research

Viruses, Vol. 11, Pages 372: Identification of RUVBL1 and RUVBL2 as Novel Cellular Interactors of the Ebola Virus Nucleoprotein
Patrick Reid Ebola virus (EBOV) is a filovirus that has become a global public health threat in recent years. EBOV is the causative agent of a severe, often fatal hemorrhagic fever. A productive viral infection relies on the successful recruitment of host factors for various stages of the viral life cycle. To date, several investigations have discovered specific host-pathogen interactions for various EBOV proteins. However, relatively little is known about the EBOV nucleoprotein (NP) with regard to host interactions. In the present study, we aimed to elucidate NP-host protein-protein interactions (PPIs). Affinity puri...
Source: Viruses - April 22, 2019 Category: Virology Authors: M. Jane Morwitzer Sarah R. Tritsch Lisa H. Cazares Michael D. Ward Jonathan E. Nuss Sina Bavari St Patrick Reid Tags: Article Source Type: research

siRNA rescues nonhuman primates from advanced Marburg and Ravn virus disease
Ebolaviruses and marburgviruses belong to the family Filoviridae and cause high lethality in infected patients. There are currently no licensed filovirus vaccines or antiviral therapies. The development of broad-spectrum therapies against members of the Marburgvirus genus, including Marburg virus (MARV) and Ravn virus (RAVV), is difficult because of substantial sequence variability. RNAi therapeutics offer a potential solution, as identification of conserved target nucleotide sequences may confer activity across marburgvirus variants. Here, we assessed the therapeutic efficacy of lipid nanoparticle (LNP) delivery of a sing...
Source: Journal of Clinical Investigation - November 7, 2017 Category: Biomedical Science Authors: Emily P. Thi, Chad E. Mire, Amy C.H. Lee, Joan B. Geisbert, Raul Ursic-Bedoya, Krystle N. Agans, Marjorie Robbins, Daniel J. Deer, Robert W. Cross, Andrew S. Kondratowicz, Karla A. Fenton, Ian MacLachlan, Thomas W. Geisbert Source Type: research

ALIX Rescues Budding of a Double PTAP/PPEY L-Domain Deletion Mutant of Ebola VP40: A Role for ALIX in Ebola Virus Egress
Ebola (EBOV) is an enveloped, negative-sense RNA virus belonging to the family Filoviridae that causes hemorrhagic fever syndromes with high-mortality rates. To date, there are no licensed vaccines or therapeutics to control EBOV infection and prevent transmission. Consequently, the need to better understand the mechanisms that regulate virus transmission is critical to developing countermeasures. The EBOV VP40 matrix protein plays a central role in late stages of virion assembly and egress, and independent expression of VP40 leads to the production of virus-like particles (VLPs) by a mechanism that accurately mimics buddi...
Source: The Journal of Infectious Diseases - September 9, 2015 Category: Infectious Diseases Authors: Han, Z., Madara, J. J., Liu, Y., Liu, W., Ruthel, G., Freedman, B. D., Harty, R. N. Tags: MOLECULAR BIOLOGY Source Type: research