Poxvirus vs. Host: Decoding the Battle for Cellular Control
"Unraveling how poxviruses hijack cellular machinery for viral replication and immune evasion"
Poxviruses stand out as a unique family of large double-stranded DNA viruses, exhibiting remarkable self-reliance and sophistication in their replication and immune evasion strategies. Encoding around 200 open reading frames (ORFs), poxviruses deploy approximately 100 immunomodulatory proteins to counteract host defenses. These viruses also possess complete DNA synthesis, transcription, mRNA processing, and cytoplasmic redox systems, enabling them to replicate exclusively within the cytoplasm of infected cells.
However, like all viruses, poxviruses rely on the host cell's translational machinery to synthesize viral proteins, as they lack ribosomes themselves. Early investigations into these intriguing viruses played a crucial role in discovering the mRNA cap and polyadenylated (polyA) tail. These elements are now recognized as essential components of eukaryotic messages, playing fundamental roles in mRNA translation. Recent studies have revealed the remarkable lengths poxviruses go to control both host and viral protein synthesis.
In this article, we delve into the central strategies employed by poxviruses and the broader battle they wage with the host cell to control the translation system. The outcome of this struggle ultimately dictates the fate of infection, influencing everything from viral replication rates to the effectiveness of the host's immune response.
Poxvirus Strategies: How Viruses Take Control
Poxviruses have evolved several key strategies to manipulate the host cell's translation machinery. These strategies ensure efficient viral protein synthesis while suppressing host defenses:
- Stimulating eIF4E Phosphorylation: Poxviruses activate signaling pathways like p38MAPK and ERK to increase eIF4E phosphorylation. This enhances the translation of viral mRNAs and suppresses the synthesis of negative regulators of the interferon (IFN) response, weakening the host's antiviral defenses.
- Concentrating eIF4F Subunits: Vaccinia virus (VacV) stimulates the formation of eIF4F complexes within cytoplasmic viral factories (VFs). The viral I3 protein binds to eIF4G, concentrating eIF4F subunits within VFs, where late viral protein synthesis occurs.
- Employing Decoy mRNAs: Poxviruses encode small, non-translated polyA mRNAs called POLADS, which act as decoys for PABP, suppressing overall translation.
- Hijacking the RQC Pathway: Poxviruses co-opt factors involved in ribosome quality control (RQC), such as ZNF598 and RPS ubiquitination, to promote viral protein synthesis. This involves turning normally repressive factors into positive ones for virus replication.
The Ongoing Evolutionary Arms Race
Poxviruses have had a profound impact on human health, both positively and negatively. Their cytoplasmic replication and self-sufficiency make them remarkable DNA viruses.
Studies of poxviruses have provided fundamental insights into mRNA processing and stability, as well as unusual modes of translation like cap-independent initiation. The adaptation of these viruses to host translation-based defenses through gene accordions highlights their evolutionary ingenuity.
Future research on poxviruses will undoubtedly reveal new insights into host-pathogen interactions and fundamental aspects of translational control, potentially paving the way for new antiviral strategies and a deeper understanding of cellular regulation.