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.

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