Comprehensive Analysis of Foot-and-Mouth Disease Virus: Genomic Structure and Functional Roles of Structural Proteins

Comprehensive Analysis of Foot-and-Mouth Disease Virus: Genomic Structure and Functional Roles of Structural Proteins

Dr.Palagiri Madhuri

PhD Scholar, Department of Animal Biochemistry, Indian Veterinary Research Institute (IVRI), Izatnagar, Bareilly-243122

Email: madhup047@gmail.com

Introduction

 Foot-and-mouth disease virus (FMDV) is a highly contagious viral pathogen affecting cloven-hoofed animals, including cattle, pigs, sheep, and goats. Understanding its biology and genomic structure is crucial for developing effective vaccines and control measures.

 Virus Classification and Structure

• Family: Picornaviridae (Picorna: Poliovirus, Insensitivity to ether, Coxsackie virus, Orphan virus, Rhinovirus and Ribonucleic acid.)
• Genus: Aphthovirus
• Virion: Non-enveloped, icosahedral capsid

Serotypes

Total of 7 serotypes are recognized namely O, A, C, Asia 1, SAT1, SAT2, SAT3 of which  O, Asia 1, and A are prevelant in our country.

Serotype O  is responsible for >85% of the outbreaks followed by A and Asia 1

Economic loss reported is approximately 20000 crore per year

Genomic Structure

FMDV has a positive-sense single-stranded RNA genome approximately 8,500 nucleotides long. The genome encodes a single polyprotein located between 5’UTR and 3’poly (A) tail which is cleaved into functional proteins by viral proteases and displays high mutation rate.

Structural Proteins

The FMDV genome encodes four main structural proteins: VP1, VP2, VP3, and VP4. These proteins form the viral capsid, protecting the viral RNA and aiding in host cell entry.

VP1 (1D)

• Function: Major antigenic protein; critical for virus attachment to host cell receptors.
• Structure: Surface-exposed; contains the G-H loop, which is involved in receptor binding and immunogenicity.
• Role in Immunity: Target for neutralizing antibodies; variations in VP1 are associated with different serotypes.

VP2 (1B)

• Function: Structural integrity and stability of the capsid.
• Structure: Partially exposed on the virus surface.
• Role in Immunity: Contributes to antigenic properties; less variable compared to VP1.

VP3 (1C)

• Function: Contributes to the structural framework of the capsid.
• Structure: Mostly buried within the capsid, with some surface exposure.
• Role in Immunity: Involved in the immune response; provides stability to the capsid structure.

VP4 (1A)

• Function: Internal protein; anchors the RNA genome to the capsid.
• Structure: Located inside the capsid, not exposed on the surface.
• Role in Immunity: Plays a role in the uncoating process during infection.

Non-Structural Proteins

In addition to structural proteins, the FMDV genome encodes several non-structural proteins (NSPs) involved in viral replication, protein processing, and modulation of the host immune response. These include:

• L (Leader protease): Cleaves the viral polyprotein and interferes with host cell machinery.
• 2A, 2B, 2C: Involved in replication and processing of the viral genome.
• 3A, 3B (VPg), 3C (Protease), 3D (RNA-dependent RNA polymerase): Crucial for RNA replication and protein processing.

Virus Replication Cycle

1. Attachment: FMDV binds to integrin receptors on the host cell surface via VP1.
2. Entry: The virus enters the host cell through receptor-mediated endocytosis.
3. Uncoating: Viral RNA is released into the cytoplasm.
4. Translation and Replication: The RNA genome is translated into a polyprotein, which is cleaved into functional viral proteins. RNA replication occurs in membrane-associated complexes.
5. Assembly: New virions are assembled in the cytoplasm.
6. Release: Mature virions are released from the host cell, often causing cell lysis.

 Conclusion

Understanding the detailed biology and genomic structure of FMDV is crucial for developing effective vaccines and antiviral strategies. The structural proteins, particularly VP1, are key targets for vaccine development due to their role in inducing protective immunity. Ongoing research aims to better understand the virus’s mechanisms of infection and immune evasion to enhance control and eradication efforts.

References

1. Grubman, M. J., & Baxt, B. (2004). Foot-and-mouth disease. Clinical Microbiology Reviews, 17(2), 465-493. DOI: 10.1128/CMR.17.2.465-493.2004
2. Sobrino, F., & Domingo, E. (2001). Foot-and-mouth disease virus: A long known virus, but a current threat. Veterinary Research, 32(1), 1-30. DOI: 10.1051/vetres:2001105
3. Belsham, G. J. (2020). Molecular biology of foot-and-mouth disease virus. Virus Research, 281, 197834. DOI: 10.1016/j.virusres.2020.197834

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