Identifying host factors as therapeutic targets for Hand, Foot and Mouth Disease through studying translational interactions between EV-A71 virus and host cells

2020 ◽  
Author(s):  
Shawn Lee Ming Yang
Keyword(s):  
Therapeutic Targets ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Host Factors ◽  
Host Cells ◽  
Foot And Mouth

scholarly journals Foot-and-Mouth Disease (FMD) Virus 3C Protease Mutant L127P: Implications for FMD Vaccine Development

2017 ◽  
Vol 91 (22) ◽  
Author(s):  
Michael Puckette ◽  
Benjamin A. Clark ◽  
Justin D. Smith ◽  
Traci Turecek ◽  
Erica Martel ◽  
...  
Keyword(s):  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Host Cells ◽  
Luciferase Reporter ◽  
Bacterial Cells ◽  
Vaccine Production ◽  
3C Protease ◽  
Fmdv Serotypes ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACT The foot-and-mouth disease virus (FMDV) afflicts livestock in more than 80 countries, limiting food production and global trade. Production of foot-and-mouth disease (FMD) vaccines requires cytosolic expression of the FMDV 3C protease to cleave the P1 polyprotein into mature capsid proteins, but the FMDV 3C protease is toxic to host cells. To identify less-toxic isoforms of the FMDV 3C protease, we screened 3C mutants for increased transgene output in comparison to wild-type 3C using a Gaussia luciferase reporter system. The novel point mutation 3C(L127P) increased yields of recombinant FMDV subunit proteins in mammalian and bacterial cells expressing P1-3C transgenes and retained the ability to process P1 polyproteins from multiple FMDV serotypes. The 3C(L127P) mutant produced crystalline arrays of FMDV-like particles in mammalian and bacterial cells, potentially providing a practical method of rapid, inexpensive FMD vaccine production in bacteria. IMPORTANCE The mutant FMDV 3C protease L127P significantly increased yields of recombinant FMDV subunit antigens and produced virus-like particles in mammalian and bacterial cells. The L127P mutation represents a novel advancement for economical FMD vaccine production.

scholarly journals Ability of Foot-and-Mouth Disease Virus To Form Plaques in Cell Culture Is Associated with Suppression of Alpha/Beta Interferon

1999 ◽  
Vol 73 (12) ◽  
pp. 9891-9898 ◽  
Author(s):  
Jarasvech Chinsangaram ◽  
Maria E. Piccone ◽  
Marvin J. Grubman
Keyword(s):  
Antiviral Activity ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Host Cells ◽  
Wild Type Virus ◽  
Beta Interferon ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Alpha Beta

ABSTRACT A genetic variant of foot-and-mouth disease virus lacking the leader proteinase coding region (A12-LLV2) is attenuated in both cattle and swine and, in contrast to wild-type virus (A12-IC), does not spread from the initial site of infection after aerosol exposure of bovines. We have identified secondary cells from susceptible animals, i.e., bovine, ovine, and porcine animals, in which infection with A12-LLV2, in contrast to A12-IC infection, does not produce plaques; this result indicates that this virus cannot spread from the site of initial infection to neighboring cells. Nevertheless, A12-LLV2 can infect these cells, but cytopathic effects and virus yields are significantly reduced compared to those seen with A12-IC infection. Reverse transcription-PCR analysis demonstrates that both A12-LLV2 and A12-IC induce the production of alpha/beta interferon (IFN-α/β) mRNA in host cells. However, only supernatants from A12-LLV2-infected cells have significant antiviral activity. The antiviral activity in supernatants from A12-LLV2-infected embryonic bovine kidney cells is IFN-α/β specific, as assayed with mouse embryonic fibroblast cells with or without IFN-α/β receptors. The results obtained with cell cultures demonstrate that the ability of A12-IC to form plaques is associated with the suppression of IFN-α/β expression and suggest a role for this host factor in the inability of A12-LLV2 to spread and cause disease in susceptible animals.

scholarly journals The Kinase STK3 Interacts with the Viral Structural Protein VP1 and Inhibits Foot-and-Mouth Disease Virus Replication

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Huisheng Liu ◽  
Qiao Xue ◽  
Qiaoying Zeng ◽  
Zixiang Zhu ◽  
Haixue Zheng
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Host Cells ◽  
Cell Protein ◽  
Structural Protein ◽  
New Information ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Fmdv Replication

Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects domestic and wild cloven-hoofed animals. The structural protein VP1 plays an important role in FMDV pathogenesis. However, the interacting partners of VP1 in host cells and the effects of these interactions in FMDV replication remain incompletely elucidated. Here, we identified a porcine cell protein, serine/threonine kinase 3 (STK3), which interacts with FMDV VP1 using the yeast two-hybrid system. The VP1-STK3 interaction was further confirmed by coimmunoprecipitation experiments in human embryonic kidney 293T and porcine kidney 15 (PK-15) cells. The carboxyl-terminal region (amino acids 180–214) of VP1 was essential for its interaction with STK3. The effects of overexpression and underexpressing of STK3 in PK-15 cells were assessed, and the results indicated that STK3 significantly inhibited FMDV replication. Our data expand the role of STK3 during viral infection, provide new information regarding the host cell kinases that are involved in viral replication, and identify potential targets for future antiviral strategies.

scholarly journals Repeated exposure to 5D9, an inhibitor of 3D polymerase, effectively limits the replication of foot-and-mouth disease virus in host cells

2013 ◽  
Vol 98 (3) ◽  
pp. 380-385 ◽  
Author(s):  
Devendra K. Rai ◽  
Elizabeth A. Schafer ◽  
Kamalendra Singh ◽  
Mark A. McIntosh ◽  
Stefan G. Sarafianos ◽  
...  
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Repeated Exposure ◽  
Host Cells ◽  
Mouth Disease Virus ◽  
Foot And Mouth

scholarly journals Foot-and-mouth disease virus 5’-terminal S fragment is required for replication and modulation of the innate immune response in host cells

Virology ◽  
2017 ◽  
Vol 512 ◽  
pp. 132-143 ◽  
Author(s):  
Anna Kloc ◽  
Fayna Diaz-San Segundo ◽  
Elizabeth A. Schafer ◽  
Devendra K. Rai ◽  
Mary Kenney ◽  
...  
Keyword(s):  
Immune Response ◽  
Disease Virus ◽  
Innate Immune Response ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Innate Immune ◽  
Host Cells ◽  
Mouth Disease Virus ◽  
Foot And Mouth

scholarly journals Fibronectin Facilitates Enterovirus 71 Infection by Mediating Viral Entry

2018 ◽  
Vol 92 (9) ◽  
Author(s):  
Qiao-qiao He ◽  
Sheng Ren ◽  
Zhang-chuan Xia ◽  
Zhi-kui Cheng ◽  
Nan-fang Peng ◽  
...  
Keyword(s):  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Host Factor ◽  
Mouth Disease ◽  
Host Cells ◽  
Ev71 Infection ◽  
Human Enterovirus ◽  
Human Enterovirus 71 ◽  
Viral Yield ◽  
Foot And Mouth

ABSTRACTFibronectin (FN) is a high-molecular-weight extracellular matrix protein that contains the RGDS motif, which is required to bind to integrins. Synthetic RGDS peptides have been reported to compete with FN to bind to the cell surface and inhibit the function of FN. Here, we identified that synthetic RGDS peptides significantly inhibit human enterovirus 71 (EV71) infection in cell cultures. In addition, mice treated with RGDS peptides and infected with EV71 had a significantly higher survival rate and a lower viral load than the control group. Because RGDS peptides affect the function of FN, we questioned whether FN may play a role in virus infection. Our study indicates that overexpression of FN enhanced EV71 infection. In contrast, knockout of FN significantly reduced viral yield and decreased the viral binding to host cells. Furthermore, EV71 entry, rather than intracellular viral replication, was blocked by FN inhibitor pretreatment. Next, we found that FN could interact with the EV71 capsid protein VP1, and further truncated-mutation assays indicated that the D2 domain of FN could interact with the N-terminal fragment of VP1. Taken together, our results demonstrate that the host factor FN binds to EV71 particles and facilitates EV71 entry, providing a potential therapy target for EV71 infection.IMPORTANCEHand, foot, and mouth disease outbreaks have occurred frequently in recent years, sometimes causing severe neurological complications and even death in infants and young children worldwide. Unfortunately, no effective antiviral drugs are available for human enterovirus 71 (EV71), one of the viruses that cause hand, foot, and mouth disease. The infection process and the host factors involved remain unknown, although several receptors have been identified. In this study, we found that the host factor fibronectin (FN) facilitated EV71 replication by interacting with EV71 particles and further mediated their entry. The RGDS peptide, an FN inhibitor, significantly inhibited EV71 replication in both RD cells and mice. In conclusion, our research identified a new host factor involved in EV71 infection, providing a new potential antiviral target for EV71 treatment.

Biophysical Measurement of Molecular Weight of Foot-and-Mouth Disease RNA Fragments

1974 ◽  
Vol 32 ◽  
pp. 262-263
Author(s):  
Sydney S. Breese ◽  
Howard L. Bachrach
Keyword(s):  
Chemical Properties ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Distilled Water ◽  
Bovine Plasma ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Carbon Coated ◽  
Rna Fragments ◽  
Physical And Chemical

Continuing studies on the physical and chemical properties of foot-and-mouth disease virus (FMDV) have included electron microscopy of RNA strands released when highly purified virus (1) was dialyzed against demlneralized distilled water. The RNA strands were dried on formvar-carbon coated electron microscope screens pretreated with 0.1% bovine plasma albumin in distilled water. At this low salt concentration the RNA strands were extended and were stained with 1% phosphotungstic acid. Random dispersions of strands were recorded on electron micrographs, enlarged to 30,000 or 40,000 X and the lengths measured with a map-measuring wheel. Figure 1 is a typical micrograph and Fig. 2 shows the distributions of strand lengths for the three major types of FMDV (A119 of 6/9/72; C3-Rezende of 1/5/73; and O1-Brugge of 8/24/73.

High resolution surface structure of foot-and-mouth disease virus

1978 ◽  
Vol 36 (2) ◽  
pp. 376-377
Author(s):  
S. S. Breese ◽  
H. L. Bachrach
Keyword(s):  
Electron Microscopy ◽  
High Resolution ◽  
Surface Structure ◽  
Disease Virus ◽  
Potassium Phosphate ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Physical Measurements ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Models for the structure of foot-and-mouth disease virus (FMDV) have been proposed from chemical and physical measurements (Brown, et al., 1970; Talbot and Brown, 1972; Strohmaier and Adam, 1976) and from rotational image-enhancement electron microscopy (Breese, et al., 1965). In this report we examine the surface structure of FMDV particles by high resolution electron microscopy and compare it with that of particles in which the outermost capsid protein VP3 (ca. 30, 000 daltons) has been split into smaller segments, two of which VP3a and VP3b have molecular weights of about 15, 000 daltons (Bachrach, et al., 1975).Highly purified and concentrated type A12, strain 119 FMDV (5 mg/ml) was prepared as previously described (Bachrach, et al., 1964) and stored at 4°C in 0. 2 M KC1-0. 5 M potassium phosphate buffer at pH 7. 5. For electron microscopy, 1. 0 ml samples of purified virus and trypsin-treated virus were dialyzed at 4°C against 0. 2 M NH4OAC at pH 7. 3, deposited onto carbonized formvar-coated copper screens and stained with phosphotungstic acid, pH 7. 3.

Hand, foot, and mouth disease preliminarily diagnosed as hypochondriasis

1990 ◽  
Vol 54 (6) ◽  
pp. 326-327
Author(s):  
MJ Davidson ◽  
DD Peters ◽  
AS Leider
Keyword(s):  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Foot And Mouth
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