negative regulation of viral transcription

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of viral transcription. [GOC:mah]

Negative regulation of viral transcription is a crucial cellular defense mechanism against viral infection. It involves a complex interplay of host and viral factors, aimed at suppressing the production of viral proteins and nucleic acids. This process can be triggered by various mechanisms, including:

* **Interferon signaling**: Upon viral infection, cells release interferons (IFNs), signaling molecules that activate downstream pathways leading to the expression of antiviral genes. These genes encode proteins that directly inhibit viral replication, including:
* **RNA-dependent protein kinase (PKR)**: PKR is activated by double-stranded RNA (dsRNA), a hallmark of viral replication. Once activated, PKR phosphorylates the eukaryotic translation initiation factor 2 alpha (eIF2α), leading to a global shutdown of protein translation and hindering viral protein synthesis.
* **2'-5'-oligoadenylate synthetase (OAS)**: OAS enzymes are activated by dsRNA and produce 2'-5'-oligoadenylates (2-5A). 2-5A then activates RNase L, an endoribonuclease that degrades viral and cellular RNA, further hindering viral replication.
* **Mx proteins**: Mx proteins are interferon-induced GTPases that directly interfere with viral replication by targeting different stages of the viral life cycle, depending on the virus.
* **Cellular microRNAs (miRNAs)**: miRNAs are small non-coding RNA molecules that regulate gene expression by binding to complementary sequences in target mRNAs, leading to their degradation or translational inhibition. Some miRNAs are specifically upregulated in response to viral infection and can target viral transcripts, suppressing viral gene expression.
* **Transcriptional repression by host transcription factors**: Host transcription factors can bind to viral promoters and inhibit viral gene transcription. For example, the transcription factor NF-κB, typically involved in inflammatory responses, can be activated by viral infection and then repress transcription of certain viral genes.
* **Direct protein-protein interactions**: Host proteins can directly interact with viral proteins involved in transcription, inhibiting their function. For instance, the cellular protein TRIM25 can interact with viral proteins, leading to their degradation and suppression of viral gene expression.

In addition to these general mechanisms, specific antiviral pathways target particular viruses. For example, the APOBEC3 family of cytidine deaminases can inhibit retroviral replication by inducing mutations in the viral genome.

Overall, negative regulation of viral transcription is a multi-layered defense mechanism that involves a dynamic interplay between host and viral factors. The precise mechanisms and outcomes vary depending on the host cell type, the infecting virus, and the specific viral genes targeted. This complex regulation is essential for maintaining cellular homeostasis and preventing uncontrolled viral replication.'
"

Proteins (1)

Compounds (1)