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R. Soc. Interface."],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:p>Life cycle processes of positive-strand (+)RNA viruses are broadly conserved across families, yet they employ different strategies to grow in the cell. Using a generalized dynamical model for intracellular (+)RNA virus growth, we decipher these life cycle determinants and their dependencies for several viruses and parse the effects of viral mutations, drugs and host cell permissivity. We show that poliovirus employs rapid replication and virus assembly, whereas the Japanese encephalitis virus leverages its higher rate of translation and efficient cellular reorganization compared to the hepatitis C virus. Stochastic simulations demonstrate infection extinction if all seeding (inoculating) viral RNA degrade before establishing robust replication critical for infection. The probability of this productive cellular infection, \u2018cellular infectivity\u2019, is affected by virus\u2013host processes and defined by early life cycle events and viral seeding. An increase in cytoplasmic RNA degradation and delay in vesicular compartment formation reduces infectivity, more so when combined. Synergy among these parameters in limiting (+)RNA virus infection as predicted by our model suggests new avenues for inhibiting infections by targeting the early life cycle bottlenecks.<\/jats:p>","DOI":"10.1098\/rsif.2021.0401","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T03:05:29Z","timestamp":1636513529000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Life cycle process dependencies of positive-sense RNA viruses suggest strategies for inhibiting productive cellular infection"],"prefix":"10.1098","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9252-1855","authenticated-orcid":true,"given":"Harsh","family":"Chhajer","sequence":"first","affiliation":[{"name":"Centre for Biosystems Science and Engineering, Indian Institute of Science, Bangalore 560012, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaseef A.","family":"Rizvi","sequence":"additional","affiliation":[{"name":"Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3329-8803","authenticated-orcid":true,"given":"Rahul","family":"Roy","sequence":"additional","affiliation":[{"name":"Centre for Biosystems Science and Engineering, Indian Institute of Science, Bangalore 560012, Karnataka, India"},{"name":"Department of Chemical Engineering, Indian Institute of Science, Bangalore 560012, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1890"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.112408.134012"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.5501\/wjv.v2.i2.32"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/v6072826"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12318"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611145200"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.10.055"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004166"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01206-18"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.07.019"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00059-11"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03539-13"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9938"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/jtbi.2002.3078"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08282"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01304-06"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003561"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1086\/428295"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.03753"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2010.09.031"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2015.09.011"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02098-17"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.00725"},{"key":"e_1_3_6_25_2","doi-asserted-by":"crossref","unstructured":"Teufel AI Liu W Draghi JA Cameron CE Wilke CO. 2020 Uncovering modeling features of viral replication dynamics from high-throughput single-cell virology experiments. bioRxiv . 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