Viral pores are everywhere

Jones et al., 2021Jones R. Bragagnolo G. Arranz Reguera J. Capping pores of alphavirus nsP1 gate membranous viral replication factories.Nature. 2021; 589: 615-619Crossref PubMed Scopus (18) Google Scholar and Zhang 2021Zhang K. Law Y.-S. M.C.Y. Tan Y.B. Wirawan M. Luo D. Structural insights into the RNA capping plasma membrane targeting by Chikungunya virus nonstructural protein 1.Cell Host Microbe. 29 (this issue): 2148-2165Abstract Full Text PDF (10) reveal cryo-EM oligomeric crown-like structure formed a membrane-associated that gates export newly synthesized from organelles. All positive-strand ([+] RNA) viruses replicate on compartments in cytoplasm infected cells. These induce massive remodeling existing host to generate unique organelles (Altan-Bonnet, 2017Altan-Bonnet N. Lipid tales transmission.Trends Cell Biol. 2017; 27: 201-213Abstract (80) Scholar). In particular, members Togaviridae, Bromoviridae, Nodaviridae, Coronaviridae families spherule-like invaginations (Figure 1). spherules are thought enhance efficiency facilitating concentration enzymes including polymerases assembly complexes , latter typically docked cytoplasmic leaflet spherule membrane. Spherules also provide secluded niche where replicated genomes shielded defenses (Miller Krijnse-Locker, 2008Miller S. Krijnse-Locker Modification intracellular structures for replication.Nat. Rev. Microbiol. 2008; 6: 363-374Crossref (522) (CHIKV), Togaviridae family member, generates its ∼50nm-diameter spherule-shaped invaginating endosome, lysosome, or (Frolov Frolova, 2019Frolov I. Frolova E.I. Molecular Virology Virus.Curr. Top. Immunol. 2019; https://doi.org/10.1007/82_2018_146Crossref (7) It was widely these remained connected cytosol channel so as enable import metabolites, translation packaging. However, composition this at neck unknown. Now, two independent studies, Scholar, both using cryo-EM, have reported it is proteinaceous structure, composed dodecamer CHIKV nsp1 proteins, assemble ring with narrow ∼7nm pore. They multifunctional pore biogenesis gating entry exit molecules between lumen spherule. addition, they show has type activity first methylates GTP m7GMP, then covalently binds it, before ultimately transferring 5′ end RNA. The obvious similarities other viruses. Nodaviridae Flock house (FHV) forms outer mitochondria 1; Unchwaniwala 2020Unchwaniwala Zhan H. Pennington Horswill den Boon J.A. Ahlquist P. Subdomain nodaviral A crown complex provides mechanistic genome replication.Proc. Natl. Acad. Sci. USA. 2020; 117: 18680-18691Crossref (19) Twelve copies FHV form size ∼50–80nm. SARS SARS-CoV-2 their ER. There, remodel ER double-membrane vesicles (DMV), morphologically similar autophagosomes. But unlike autophagosomes, DMVs not closed off Recently, Wolff 2020Wolff Limpens R.W.A.L. Zevenhoven-Dobbe J.C. Laugks U. Zheng de Jong A.W.M. Koning R.I. Agard D.A. Grünewald Koster A.J. al.A molecular spans double coronavirus organelle.Science. 369: 1395-1398Crossref revealed presence cylindrical spanning DMV membrane, six nsp3 protein. Similar CHIKV, allows be released packaging and/or translation; components appear dynamically interact polymerase possibly factors guide molecules. Despite evolutionary differences among organelle origin organelles, prevalence indicates fundamental role synthesis trafficking. Given this, highly likely will discovered necks peroxisome chloroplast membranes Tombusviridae Tymoviridae members, respectively Viral share striking morphological functional eukaryotic nuclear (NPC) 1): span regulate import/export nucleic acids, metabolites. Furthermore, indicating important formation, NPC nucleoporins and, nsp1, conserved sequence level across eukaryotes Alphaviridae respectively. supramolecular complexes, different proteins evolved carry out functions, done during transcription prior export, multiple functions fewer components. For example, while there sets filaments acids C-terminal disordered loops, facing inside catalyze only but trafficking cytosol, all ensuring double-stranded replicative remains behind. Though yet determined, domains outside cytoplasm. NPCs, major driving force been duplication cyclization effective permeability, selectivity, transport many sizes cargo (Beck Hurt, 2017Beck Hurt E. complex: understanding function through structural insight.Nat. Mol. 18: 73-89Crossref (319) From an perspective, may hold true due limitations how much can encoded given (+) viruses, become consolidated within one virally such nsp1. Finally, do work alone biogenesis, morphogenesis negative curvature multivesicular bodies frequently hijacked. instance, Tomato bushy stunt (TBSV) requires endosomal sorting required I (ESCRT-I) Vps23p (mammalian Tsg101) peroxisomal yeast; Bromoviruses recruit ESCRT-1, Vps2, Vps24 along reticulons formation Diaz 2015Diaz A. Ollwerther Wang X. ESCRT Bromovirus compartment function.PLoS Pathog. 2015; 11: e1004845Crossref (4) were recently identified critical replication, whether them unclear (Torii 2020Torii Orba Y. Sasaki Tabata Wada Carr Hobson-Peters Hall R.A. Takada Fukuhara T. al.Host recruited chikungunya infection cycle.J. Chem. 295: 7941-7957Abstract summary, studies elegantly highlight Swiss army knife nature raise new questions regarding determinants selectivity; significance viruses; contribution lipids function. Ultimately, significantly add growing body data importance regulating SARS-CoV-2. authors thank NIH Medical Arts personnel Erina He, Alan Hoofring, Ethan Tyler help designing figure. Intramural NHLBI / funds supported M.K. N.A.B. 1Zhang al.Cell & MicrobeMarch 16, 2021In BriefThe architecture al. dodecameric which targets catalyzes key steps capping. Full-Text Open Archive