2020/01/28 by Ervin Fodor · 1 citation
Environmental Science · Immunology and Microbiology · Medicine · #Bacteriophages and microbial interactions #Biology #Computational biology #Gene #Genetics #RNA #Rabies #Rabies epidemiology and control #Rabies virus #Viral Infections and Outbreaks Research #Virology #Virus
paper · pdf · doi:10.1073/pnas.2000120117
openalex publication_date 2020/01/28 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/15
Rabies virus (RABV) is the causative agent of a fatal neurological disease in humans and animals. It is transmitted to humans from infected animals, mainly domestic dogs, through their saliva by biting or by scratching. Rabies is controlled by vaccination of domestic dogs and cats, but RABV nevertheless kills more than 50,000 people annually, especially in developing countries where vaccination rates in domestic dogs are lower. In humans, rabies is preventable by vaccination prior to or immediately after exposure, but there are no specific antiviral drugs available that target the virus directly (1). In PNAS, Horwitz et al. (2) present a high-resolution electron cryomicroscopy structure of the RNA synthesis machine of RABV, providing valuable mechanistic insight into its activities and opening up the way toward developing antiviral approaches for this fatal virus. RABV belongs to the group of negative-strand RNA viruses that includes many human pathogens such as the influenza viruses, respiratory syncytial virus (RSV), Ebola virus, and measles virus. The genomes of these viruses consist of one or more single-stranded, negative-sense RNA molecules that are always assembled with multiple copies of viral nucleoprotein (N) into megadalton-sized complexes (3). In order to initiate infection, viruses such as RABV must first transcribe their negative-sense RNA into mRNA and therefore must carry an RNA-dependent RNA polymerase within their infectious particle. These viral polymerases are multifunctional machines that not only transcribe the negative-strand RNA into mRNA but also replicate the genome through a complementary replicative intermediate, the antigenome. In addition to catalyzing RNA synthesis, these polymerases also ensure that viral transcripts are protected with a 5′-cap structure. This is achieved either by a cap-snatching mechanism that involves stealing caps from host capped RNAs through cap-binding and endonuclease functions, or de novo synthesis of a 5′-cap structure using capping and methyltransferase enzymes, which are … [↵][1]1Email: ervin.fodoratpath.ox.ac.uk. [1]: #xref-corresp-1-1