English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Poxviruses are truly remarkable pathogens. The most notorious, variola virus (VarV), is thought to have emerged in Africa around 3,000–4,000 years ago. From there, VarV swept across the world causing smallpox, a disease that killed more people than all other infectious agents in recorded history combined [1]. Noticing apparent immunity in milkmaids, Edward Jenner inoculated naïve children with cowpox, resulting in protection against smallpox and ushering in the era of vaccines (“vacca” being Latin for “cow”). Intriguingly, we now use a close relative of VarV, vaccinia virus (VacV), both as a vaccine and laboratory prototype for poxvirus infection. Mysteriously, we don’t know the true origin or natural host of VacV because of the lack of records and way in which vaccines were generated and shared across the globe in the earliest attempts to control smallpox [2]. Despite its mysterious origins, VacV was instrumental in making VarV the only human pathogen to have been successfully eradicated. This medical milestone was possible in part because of the fortunate fact that VarV only infects humans, leaving it with no reservoir in which to hide. Serious threats remain from the potential reintroduction of VarV as well as the ongoing emergence and adaptation of new or zoonotic poxviruses. However, these viruses have also become invaluable tools in oncolytic gene therapy and as vaccine vectors in modern medicine. As if their clinical history wasn’t striking enough, their mode of replication and level of selfsufficiency is equally remarkable [3]. While other mammalian DNA viruses must reach the nucleus to replicate, poxviruses, together with African swine fever virus (the sole member of the Asfaviridae), replicate entirely in the cytoplasm within compartments called viral factories (VFs). Poxviruses can do this because their large genomes encode hundreds of proteins that include their own dedicated RNA and DNA polymerases, transcription and mRNA biogenesis factors, and their own cytoplasmic redox system. Cleverly, factors controlling early gene expression are generated late in infection and packaged into new virions. As such, upon entry and fusion, poxviruses rapidly transcribe and extrude early mRNAs into the host cell cytoplasm. Synthesis of early viral proteins leads to core uncoating and progression of the viral gene expression program. Remodeling of the endoplasmic reticulum establishes the VF, the site of viral DNA replication and formation of progeny virions. However, despite their incredible self-sufficiency, poxviruses, like all viruses, remain entirely dependent on host ribosomes to translate their mRNAs [4]. This is because, beyond the plethora of regulatory initiation, elongation, and termination factors utilized by their eukaryotic hosts, ribosomes alone consist of approximately 79 protein and 4 rRNA subunits. Thus, encoding their own translation system is something apparently beyond the coding capacity of even the largest viruses identified to date, the mimiviruses, which infect amoeba and fall into the same family of nucleocytoplasmic large DNA viruses (NCLDVs) as poxviruses.

Poxviruses: Slipping and sliding through transcription and translation