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UniProt release 2019_04

Published May 8, 2019

Headline

A pox on your messenger

Millions of years of coexistence between viruses and their hosts has imposed a selection pressure on hosts to develop the most efficient defense systems possible, while viruses evolve more and more complex strategies to escape them. New findings from James B. Eaglesham and co-workers describe how viruses block second messenger production to evade innate immunity.

The innate immune system is the first line of host defense; it relies on pattern recognition receptors (PRRs) to detect pathogen-specific molecules. The enzyme cyclic 2',3'-cyclic GMP-AMP (cGAMP) synthase cGAS is a PRR that recognizes cytosolic double-stranded DNA, a marker for viral infection, and catalyzes the formation of cGAMP. cGAMP in turn activates STING (also known as TMEM173) and type I interferon and NF-kappa-B responses, leading to a potent anti-viral state. The poxin family of viral proteins cleave cytosolic 2',3'-cGAMP into linear Gp[2'-5']Ap[3'], thereby preventing the activation of STING and the resulting induction of the host immune response. Not surprisingly, poxins are required for efficient viral replication in vivo.

Poxins are found in poxviruses, a large family of DNA viruses infecting mammalian cells, and baculoviruses, which target insect cells. The active site is conserved between poxviruses, including vaccinia virus poxin, and baculoviruses, an amazing observation considering the evolutionary distance between these viral families. Even more surprising is the presence of an enzymatically active poxin homolog in the silk moth Bombyx mori and other moth and butterfly genomes! The current hypothesis for the spread of poxins between insects and insect and mammalian viruses is that poxviruses and baculoviruses can share overlapping host tropisms and readily acquire genes through homologous recombination.

UniProtKB/Swiss-Prot poxin entries have been updated and should not escape your attention.

UniProtKB news

Removal of the cross-references to HOVERGEN

Cross-references to HOVERGEN have been removed.

Removal of the cross-references to ProteinModelPortal

Cross-references to ProteinModelPortal have been removed.

In an attempt to improve access to modelling data, we now add a link to the SWISS-MODEL-Workspace for all entries that are not already cross-referenced to the SWISS-MODEL Repository (SMR). This new link will allow users to start a new homology modelling project.

Removal of the cross-references to UniGene

Cross-references to UniGene have been removed.

Changes to the controlled vocabulary of human diseases

New diseases:

Changes to keywords

New keywords:

Deleted keywords:

  • Immunoglobulin C region
  • Immunoglobulin V region
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