Hepatitis A virus internal ribosome entry site (IRES)

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RF00228

Hepatitis A virus internal ribosome entry site (IRES) is a crucial element in the genetic structure of the Hepatitis A virus (HAV), a significant cause of viral hepatitis. The IRES is a specialized RNA sequence located in the non-coding region of the virus's genome, enabling the initiation of protein synthesis independently of the cap structure typically found on eukaryotic mRNAs. This mechanism is essential for the virus's ability to hijack the host's ribosomes and initiate the translation of its own proteins, a key step in viral replication and pathogenesis.

Structure and Function[edit | edit source]

The HAV IRES is characterized by its unique secondary and tertiary RNA structure, which allows it to directly bind to the host's ribosomes. Unlike the cap-dependent mechanism that most eukaryotic mRNAs use for translation initiation, the IRES does not require certain initiation factors, making it a novel target for antiviral research. The structure of the HAV IRES facilitates a cap-independent mode of translation, ensuring the viral proteins can be synthesized even under conditions where cap-dependent translation is inhibited, such as during viral infection.

Role in Viral Replication[edit | edit source]

The ability of the HAV IRES to initiate translation directly impacts the virus's replication cycle. By bypassing the need for cap-dependent translation initiation, HAV can efficiently exploit the host's translational machinery to produce the viral proteins necessary for its replication. This mechanism is particularly advantageous under conditions where the host's cellular defenses might otherwise inhibit viral protein synthesis.

Implications for Research and Treatment[edit | edit source]

Understanding the structure and function of the HAV IRES has significant implications for the development of antiviral therapies. Targeting the IRES with small molecules or antisense oligonucleotides could potentially inhibit HAV replication, offering a novel approach to treating hepatitis A. Moreover, the study of the HAV IRES contributes to the broader understanding of viral translation mechanisms, which could inform the development of therapeutic strategies against other viruses employing similar strategies for protein synthesis.

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Contributors: Prab R. Tumpati, MD