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V protein of paramyxovirus

Preeti Bharaj, Yao E Wang, Brian E Dawes, Tatyana E Yun, Arnold Park, Benjamin Yen, Christopher F Basler, Alexander N Freiberg, Benhur Lee, Ricardo Rajsbaum
For efficient replication, viruses have developed mechanisms to evade innate immune responses, including the antiviral type-I interferon (IFN-I) system. Nipah virus (NiV), a highly pathogenic member of the Paramyxoviridae family (genus Henipavirus), is known to encode for four P gene-derived viral proteins (P/C/W/V) with IFN-I antagonist functions. Here we report that NiV matrix protein (NiV-M), which is important for virus assembly and budding, can also inhibit IFN-I responses. IFN-I production requires activation of multiple signaling components including the IκB kinase epsilon (IKKε)...
September 2016: PLoS Pathogens
D F Young, J Andrejeva, X Li, F Inesta-Vaquera, C Dong, V H Cowling, S Goodbourn, R E Randall
UNLABELLED: We have previously shown that IFIT1 is primarily responsible for the antiviral action of interferon (IFN) alpha/beta against parainfluenza virus type 5 (PIV5), selectively inhibiting the translation of PIV5 mRNAs. Here we report that while PIV2, PIV5, and mumps virus (MuV) are sensitive to IFIT1, nonrubulavirus members of the paramyxoviridae such as PIV3, Sendai virus (SeV), and canine distemper virus (CDV) are resistant. The IFIT1 sensitivity of PIV5 was not rescued by coinfection with an IFIT1-resistant virus (PIV3), demonstrating that PIV3 does not specifically inhibit the antiviral activity of IFIT1 and that the inhibition of PIV5 mRNAs is regulated by cis-acting elements...
October 15, 2016: Journal of Virology
Michelle D Audsley, David A Jans, Gregory W Moseley
Genome replication and virion production by most negative-sense RNA viruses (NSVs) occurs exclusively in the cytoplasm, but many NSV-expressed proteins undergo active nucleocytoplasmic trafficking via signals that exploit cellular nuclear transport pathways. Nuclear trafficking has been reported both for NSV accessory proteins (including isoforms of the rabies virus phosphoprotein, and V, W and C proteins of paramyxoviruses) and for structural proteins. Trafficking of the former is thought to enable accessory functions in viral modulation of antiviral responses including the type I IFN system, but the intranuclear roles of structural proteins such as nucleocapsid and matrix proteins, which have critical roles in extranuclear replication and viral assembly, are less clear...
October 2016: Journal of General Virology
X Qiu, Q Fu, C Meng, S Yu, Y Zhan, L Dong, T Ren, Y Sun, L Tan, C Song, X Han, C Ding
UNLABELLED: As a paramyxovirus, Newcastle disease virus (NDV) has the ability to edit its P (phosphoprotein) gene to synthesize three kinds of viral protein (P, V and W). It is technically very difficult to differentiate P, V and W mRNAs, and little was known about NDV regulation of RNA-editing frequency. To investigate the rules of NDV RNA editing, the ratio of the P gene-derived transcripts (P, V and W) was determined by sequencing at different time points post-infection. The results showed unstable ratio of V and W mRNA at different time points, and the frequency of NDV editing was significantly increased at the early period of infection (P  KEYWORDS: Newcastle disease virus; phosphoprotein; RNA editing; G insertion...
March 2016: Acta Virologica
Jacquelyn A Stone, Anthony V Nicola, Linda G Baum, Hector C Aguilar
O-linked glycosylation is a ubiquitous protein modification in organisms belonging to several kingdoms. Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. Reportedly, there is no single function attributed to O-glycans for the significant paramyxovirus family. The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses...
February 2016: PLoS Pathogens
Xusheng Qiu, Qiang Fu, Chunchun Meng, Shengqing Yu, Yuan Zhan, Luna Dong, Cuiping Song, Yingjie Sun, Lei Tan, Shunlin Hu, Xiaoquan Wang, Xiaowen Liu, Daxin Peng, Xiufan Liu, Chan Ding
Newcastle disease virus (NDV) V protein is considered as an effector for IFN antagonism, however, the mechanism remains unknown. In this study, the expression of STAT1 and phospho-STAT1 in cells infected with NDV or transfected with V protein-expressing plasmids were analyzed. Our results showed that NDV V protein targets phospho-STAT1 reduction in the cells depends on the stimulation of IFN-α. In addition, a V-deficient genotype VII recombinant NDV strain rZJ1-VS was constructed using reverse genetic technique to confirm the results...
2016: PloS One
Olga V Matveeva, Zong S Guo, Svetlana A Shabalina, Peter M Chumakov
Oncolytic paramyxoviruses include some strains of Measles, Mumps, Newcastle disease, and Sendai viruses. All these viruses are well equipped for promoting highly specific and efficient malignant cell death, which can be direct and/or immuno-mediated. A number of proteins that serve as natural receptors for oncolytic paramyxoviruses are frequently overexpressed in malignant cells. Therefore, the preferential interaction of paramyxoviruses with malignant cells rather than with normal cells is promoted. Due to specific genetic defects of cancer cells in the interferon (IFN) and apoptotic pathways, viral replication has the potential to be promoted specifically in tumors...
2015: Molecular Therapy Oncolytics
Giuseppe Pisanelli, Maudry Laurent-Rolle, Balaji Manicassamy, Alan Belicha-Villanueva, Juliet Morrison, Bernardo Lozano-Dubernard, Felipa Castro-Peralta, Giuseppe Iovane, Adolfo García-Sastre
La Piedad Michoacán Mexico Virus (LPMV) is a member of the Rubulavirus genus within the Paramyxoviridae family. LPMV is the etiologic agent of "blue eye disease", causing a significant disease burden in swine in Mexico with long-term implications for the agricultural industry. This virus mainly affects piglets and is characterized by meningoencephalitis and respiratory distress. It also affects adult pigs, causing reduced fertility and abortions in females, and orchitis and epididymitis in males. Viruses of the Paramyxoviridae family evade the innate immune response by targeting components of the interferon (IFN) signaling pathway...
February 2, 2016: Virus Research
Kim G Lieu, Glenn A Marsh, Lin-Fa Wang, Hans J Netter
Immune evasion by the lethal henipaviruses, Hendra (HeV) and Nipah virus, is mediated by its interferon (IFN) antagonist P gene products, phosphoprotein (P), and the related V and W proteins, which can target the signal transducer and activator of transcription 1 (STAT1) and STAT2 proteins to inhibit IFN/STAT signaling. However, it is not clear if the recently identified non-pathogenic Henipavirus, Cedar paramyxovirus (CedPV), is also able to antagonize the STAT proteins. We performed comparative studies between the HeV P gene products (P/V/W) and CedPV-P (CedPV does not encode V or W) and demonstrate that differences exist in their ability to engage the STAT proteins using immunoprecipitation and quantitative confocal microscopic analysis...
December 2015: Antiviral Research
Yang Yang, James Zengel, Minghao Sun, Katrina Sleeman, Khalid Amine Timani, Jason Aligo, Paul Rota, Jianguo Wu, Biao He
UNLABELLED: Paramyxoviruses include many important animal and human pathogens. The genome of parainfluenza virus 5 (PIV5), a prototypical paramyxovirus, encodes a V protein that inhibits viral RNA synthesis. In this work, the mechanism of inhibition was investigated. Using mutational analysis and a minigenome system, we identified regions in the N and C termini of the V protein that inhibit viral RNA synthesis: one at the very N terminus of V and the second at the C terminus of V. Furthermore, we determined that residues L16 and I17 are critical for the inhibitory function of the N-terminal region of the V protein...
December 2015: Journal of Virology
J A Garcia, H L Ferreira, F V Vieira, R Gameiro, A L Andrade, F R Eugênio, E F Flores, T C Cardoso
Oncolytic virotherapy is a novel strategy for treatment of cancer in humans and companion animals as well. Canine distemper virus (CDV), a paramyxovirus, has proven to be oncolytic through induction of apoptosis in canine-derived tumour cells, yet the mechanism behind this inhibitory action is poorly understood. In this study, three human mammary tumour cell lines and one canine-derived adenofibrosarcoma cell line were tested regarding to their susceptibility to CDV infection, cell proliferation, apoptosis, mitochondrial membrane potential and expression of tumour necrosis factor-alpha-induced protein 8 (TNFAIP8)...
September 16, 2015: Veterinary and Comparative Oncology
Benjamin A Satterfield, Robert W Cross, Karla A Fenton, Krystle N Agans, Christopher F Basler, Thomas W Geisbert, Chad E Mire
The viral determinants that contribute to Nipah virus (NiV)-mediated disease are poorly understood compared with other paramyxoviruses. Here we use recombinant NiVs (rNiVs) to examine the contributions of the NiV V and W proteins to NiV pathogenesis in a ferret model. We show that a V-deficient rNiV is susceptible to the innate immune response in vitro and behaves as a replicating non-lethal virus in vivo. Remarkably, rNiV lacking W expression results in a delayed and altered disease course with decreased respiratory disease and increased terminal neurological disease associated with altered in vitro inflammatory cytokine production...
2015: Nature Communications
Jennifer E Schuster, John V Williams
Human metapneumovirus (HMPV), a paramyxovirus identified in 2001, is a leading cause of respiratory tract infections in both children and adults. Seroprevalence studies demonstrate that the primary infection occurs before the age of 5 years, and humans are reinfected throughout life. The four subgroups of HMPV occur with year-to-year variability, and infection with one subgroup confers some serologic cross-protection. Experimental vaccines elicit a humoral response in both animal and human models and have been used to identify antigenic determinants...
October 2014: Microbiology Spectrum
Nicole B Glennon, Omar Jabado, Michael K Lo, Megan L Shaw
UNLABELLED: Bats are important reservoirs for several viruses, many of which cause lethal infections in humans but have reduced pathogenicity in bats. As the innate immune response is critical for controlling viruses, the nature of this response in bats and how it may differ from that in other mammals are of great interest. Using next-generation transcriptome sequencing (mRNA-seq), we profiled the transcriptional response of Pteropus vampyrus bat kidney (PVK) cells to Newcastle disease virus (NDV), an avian paramyxovirus known to elicit a strong innate immune response in mammalian cells...
August 2015: Journal of Virology
Andrew K Hastings, John J Erickson, Jennifer E Schuster, Kelli L Boyd, Sharon J Tollefson, Monika Johnson, Pavlo Gilchuk, Sebastian Joyce, John V Williams
UNLABELLED: Type I IFN signaling, which is initiated through activation of the alpha interferon receptor (IFNAR), regulates the expression of proteins that are crucial contributors to immune responses. Paramyxoviruses, including human metapneumovirus (HMPV), have evolved mechanisms to inhibit IFNAR signaling, but the specific contribution of IFNAR signaling to the control of HMPV replication, pathogenesis, and adaptive immunity is unknown. We used IFNAR-deficient (IFNAR(-/-)) mice to assess the effect of IFNAR signaling on HMPV replication and the CD8(+) T cell response...
April 2015: Journal of Virology
Qian Liu, Birgit Bradel-Tretheway, Abrrey I Monreal, Jonel P Saludes, Xiaonan Lu, Anthony V Nicola, Hector C Aguilar
UNLABELLED: Membrane fusion is essential for paramyxovirus entry into target cells and for the cell-cell fusion (syncytia) that results from many paramyxoviral infections. The concerted efforts of two membrane-integral viral proteins, the attachment (HN, H, or G) and fusion (F) glycoproteins, mediate membrane fusion. The emergent Nipah virus (NiV) is a highly pathogenic and deadly zoonotic paramyxovirus. We recently reported that upon cell receptor ephrinB2 or ephrinB3 binding, at least two conformational changes occur in the NiV-G head, followed by one in the NiV-G stalk, that subsequently result in F triggering and F execution of membrane fusion...
February 2015: Journal of Virology
Matthew Landowski, Jeffrey Dabundo, Qian Liu, Anthony V Nicola, Hector C Aguilar
UNLABELLED: Virus-cell membrane fusion is essential for enveloped virus infections. However, mechanistic viral membrane fusion studies have predominantly focused on cell-cell fusion models, largely due to the low availability of technologies capable of characterizing actual virus-cell membrane fusion. Although cell-cell fusion assays are valuable, they do not fully recapitulate all the variables of virus-cell membrane fusion. Drastic differences between viral and cellular membrane lipid and protein compositions and curvatures exist...
December 2014: Journal of Virology
Denis K Byarugaba, Kizito K Mugimba, John B Omony, Martin Okitwi, Agnes Wanyana, Maxwell O Otim, Halid Kirunda, Jessica L Nakavuma, Angélique Teillaud, Mathilde C Paul, Mariette F Ducatez
BACKGROUND: Newcastle disease is still a serious disease of poultry especially in backyard free-range production systems despite the availability of cross protective vaccines. Healthy-looking poultry from live bird markets have been suspected as a major source of disease spread although limited studies have been conducted to ascertain the presence of the virulent strains in the markets and to understand how they are related to outbreak strains. METHODS: This study evaluated the occurrence of Newcastle disease virus in samples collected from poultry in live bird markets across Uganda...
2014: Virology Journal
Meredith E Davis, May K Wang, Linda J Rennick, Florian Full, Sebastian Gableske, Annelies W Mesman, Sonja I Gringhuis, Teunis B H Geijtenbeek, W Paul Duprex, Michaela U Gack
The cytosolic sensor MDA5 is crucial for antiviral innate immune defense against various RNA viruses including measles virus; as such, many viruses have evolved strategies to antagonize the antiviral activity of MDA5. Here, we show that measles virus escapes MDA5 detection by targeting the phosphatases PP1α and PP1γ, which regulate MDA5 activity by removing an inhibitory phosphorylation mark. The V proteins of measles virus and the related paramyxovirus Nipah virus interact with PP1α/γ, preventing PP1-mediated dephosphorylation of MDA5 and thereby its activation...
July 9, 2014: Cell Host & Microbe
Hisashi Akiyama, Caitlin Miller, Hiren V Patel, Steven C Hatch, Jacob Archer, Nora-Guadalupe P Ramirez, Suryaram Gummuluru
UNLABELLED: Human immunodeficiency virus type 1 (HIV-1) exploits dendritic cells (DCs) to promote its transmission to T cells. We recently reported that the capture of HIV-1 by mature dendritic cells (MDCs) is mediated by an interaction between the glycosphingolipid (GSL) GM3 on virus particles and CD169/Siglec-1 on MDCs. Since HIV-1 preferentially buds from GSL-enriched lipid microdomains on the plasma membrane, we hypothesized that the virus assembly and budding site determines the ability of HIV-1 to interact with MDCs...
August 2014: Journal of Virology
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