Foot-and-Mouth Disease Virus Modulates Cellular Vimentin for Virus Survival

Abstract

Foot-and-mouth disease virus (FMDV), the causative agent of foot-and-mouth disease, is an Aphthovirus within the Picornaviridae family. During infection with FMDV, several host cell membrane rearrangements occur to form sites of viral replication. FMDV protein 2C is part of the replication complex and thought to have multiple roles during virus replication. To better understand the role of 2C in the process of virus replication, we have been using a yeast two-hybrid approach to identify host proteins that interact with 2C. We recently reported that cellular Beclin1 is a natural ligand of 2C and that it is involved in the autophagy pathway, which was shown to be important for FMDV replication. Here, we report that cellular vimentin is also a specific host binding partner for 2C. The 2C-vimentin interaction was further confirmed by coimmunoprecipitation and immunofluorescence staining to occur in FMDV-infected cells. It was shown that upon infection a vimentin structure forms around 2C and that this structure is later resolved or disappears. Interestingly, overexpression of vimentin had no effect on virus replication; however, overexpression of a truncated dominant-negative form of vimentin resulted in a significant decrease in viral yield. Acrylamide, which causes disruption of vimentin filaments, also inhibited viral yield. Alanine scanning mutagenesis was used to map the specific amino acid residues in 2C critical for vimentin binding. Using reverse genetics, we identified 2C residues that are necessary for virus growth, suggesting that the interaction between FMDV 2C and cellular vimentin is essential for virus replication.

Suppression of Vimentin Phosphorylation by the Avian Reovirus p17 through Inhibition of CDK1 and Plk1 Impacting the G2/M Phase of the Cell Cycle

“…Several previous studies have suggested that vimentin plays an important role in several virus infections [51–58]. In this work, we found that inhibition of vimentin by IDPN diminished virus yield, implying that vimentin plays a role in virus replication.…”

Proteomic-Based Approach To Gain Insight into Reprogramming of THP-1 Cells Exposed to Leishmania donovani over an Early Temporal Window

“…Proinflammatory cytokines such as TNF-␣ can trigger its secretion, while IL-10 (Th2 cytokine) is known to block its secretion in a PKC-dependent manner (62). Vimentin is essential for the replication of foot-andmouth disease virus, and it has been deregulated during Toxoplasma infection (28,63). An early low abundance (ϳ0.58-fold at 12 h) followed by an augmentation of its abundance (ϳ1.74-fold at 24 h and ϳ2.2-fold at 48 h) and gene expression (Fig.…”

Interaction of Foot-and-Mouth Disease Virus Nonstructural Protein 3A with Host Protein DCTN3 Is Important for Viral Virulence in Cattle

“…In our previous work that focused on cellular proteins that interact with FMDV nonstructural protein 2C, we determined that viral 2C was able to bind cellular Beclin1 to prevent autophagosomelysosome fusion, favoring virus survival (27). We also discovered that 2C binds with cellular vimentin, a protein that forms a cage-like structure around 2C early during infection but must later be resolved for virus replication to progress (13). Here, we report that FMDV nonstructural protein 3A binds to DCTN3, a subunit of the dynactin complex that acts as a cofactor for the microtubule-base motor dynein.…”

“…Using a similar approach, we previously reported that FMDV 2C was able to bind cellular Beclin1 and vimentin facilitating virus replication (13). Here, we report that FMDV nonstructural protein 3A binds to DCTN3 (dynactin 3), a subunit of the dynactin complex that acts as a cofactor for the microtubule-base motor dynein.…”