APOBEC (Apolipoprotein B mRNA Editing Catalytic Polypeptide)

Why in the News?

Since smallpox was eradicated in 1980, research on mpox has highlighted how the virus mutates, particularly through the APOBEC family of immune system proteins.

About APOBEC

• APOBEC (Apolipoprotein B mRNA Editing Enzyme, Catalytic Polypeptide-Like) is a family of proteins involved in regulating the genetic material of viruses and cells.
• They are part of the human immune system and play a crucial role in protecting against viral infections by editing RNA and DNA.
• APOBEC consists of several enzymes, with APOBEC1, APOBEC3 family members being the most well-known.
• There are 11 identified members of the APOBEC family, primarily named APOBEC1, APOBEC2, and APOBEC3, with APOBEC3 being the most studied due to its antiviral properties.
• It has a Zinc Finger Domain, which is essential for their enzymatic activity and ability to bind to DNA or RNA.
• APOBEC proteins are found in various tissues and cells, but they are notably present in the immune cells such as T-cells, B-cells, and macrophages.
• Role in Immune Defense:
  • APOBEC proteins contribute to the innate immune response by editing viral genomes, preventing the replication of viruses, and reducing the ability of viruses to establish infections.
  • They are known to be cytosine deaminases, which means they modify cytosine bases in nucleic acids to uracil, leading to mutations that can prevent successful viral replication.
  • APOBEC proteins target the genomes of several viruses, including retroviruses (like HIV), hepatitis B virus, and poxviruses (such as mpox and smallpox).

Functions of APOBEC Proteins:

• DNA Editing: APOBEC proteins can deaminate cytosine bases in single-stranded DNA, converting them into uracil, which can lead to mutations.
  • This introduces errors in the viral genome and inhibits replication.
• RNA Editing: Some APOBEC proteins, like APOBEC1, are involved in editing mRNA. In the case of APOBEC1, it helps edit the mRNA of apolipoprotein B, which is crucial for lipid metabolism.
• Antiviral Activity: APOBEC3 proteins, particularly APOBEC3G, inhibit the replication of HIV and other retroviruses by editing viral DNA during reverse transcription.
  • They also reduce the replication of poxviruses (such as mpox), making them crucial in controlling infections caused by these viruses.
• Cytosine Deamination in Viral RNA: APOBEC proteins induce mutations in viral RNA, reducing the virus’s ability to efficiently replicate and spread. This helps prevent viral evolution and adaptation.
• Inhibition of Viral Resistance: By causing mutations in viral genomes, APOBEC proteins prevent viruses from easily developing resistance to the immune system’s defenses.
• Interaction with Other Immune Mechanisms: APOBEC proteins work in concert with other immune mechanisms, like interferons, to enhance antiviral responses and limit infections.