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

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.

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

BioMed Research International ◽

10.1155/2017/2481348 ◽

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.

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

Virology ◽

10.1016/j.virol.2017.08.036 ◽

2017 ◽

Vol 512 ◽

pp. 132-143 ◽

Cited By ~ 12

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

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

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100082741 ◽

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.

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