[{"command":"settings","settings":{"pluralDelimiter":"\u0003","suppressDeprecationErrors":true,"entitySetting":{"type":"bibcite_reference","bundle":"journal_article","mapping":{"node":{"blog":"blog","class":"classes","events":"calendar","faq":"faq","link":"links","news":"news","page":"","person":"people","presentation":"presentations","software_project":"software","software_release":"software"},"bibcite_reference":{"*":"publications"},"paragraph":{"class_material":"classes"}},"viewmode":"teaser"},"user":{"uid":0,"permissionsHash":"7f1a171f8b0b5a764cab6d1b118f6329cfc3469f3145adbaf7b7495bbf60a5ea"}},"merge":true},{"command":"add_js","selector":"body","data":[{"src":"\/files\/js\/js_DOoUrEhS-bkVvWBnZGMbXVBHnh5Ov7QOD3C6k4k3980.js?scope=footer\u0026delta=0\u0026language=en\u0026theme=texasbio_eligendi\u0026include=eJzLL44vKE3KyUxOLMnMzyvWTykqLUjM0ctHFdbLzSxO1ikrzixJ1U_OzytJrSgpTcxxK83JCctMLQcAsjEbVw"}]},{"command":"insert","method":"replaceWith","selector":"#","data":"\n  \u003Cdiv class=\u0022field field--name-field-widget-title field--type-string field--label-visually_hidden field--mode-full\u0022\u003E\n    \u003Cdiv class=\u0022field--label sr-only\u0022\u003EWidget Title\u003C\/div\u003E\n              \u003Cdiv class=\u0022field--item\u0022\u003EIdentification and validation of virus in cultured cells and animal models of infection\u003C\/div\u003E\n          \u003C\/div\u003E\n\n\u003Cul  id=\u0022list-of-posts\u0022 more_link_id=\u0022node-readmore\u0022 class=\u0022publications view-teaser grid-view\u0022\u003E\n \u003Cli\u003E\n\u003Carticle class=\u0022bibcite-reference bibcite bibcite--teaser\u0022\u003E\n  \n  \n  \n\n  \u003Cdiv class=\u0022bibcite__content\u0022\u003E\n    \u003Cdiv class=\u0022bibcite-citation\u0022\u003E\n      \u003Cdiv class=\u0022csl-bib-body\u0022\u003E\u003Cdiv class=\u0022csl-entry\u0022\u003EOladunni, Fatai S, Jun-Gyu Park, Paula A Pino, Olga Gonzalez, Anwari Akhter, Anna Allu\u00e9-Guardia, Ang\u00e9lica Olmo-Font\u00e1nez, et al. (2020) 2020. \u201c\u003Ca href=\u0022\/lms-lab\/publications\/lethality-sars-cov-2-infection-k18-human-angiotensin-converting-enzyme-2-transgenic\u0022 hreflang=\u0022en\u0022\u003ELethality of SARS-CoV-2 Infection in K18 Human Angiotensin-Converting Enzyme 2 Transgenic Mice.\u003C\/a\u003E\u201d. \u003Ci\u003ENature Communications\u003C\/i\u003E 11 (1): 6122. https:\/\/doi.org\/10.1038\/s41467-020-19891-7.\u003C\/div\u003E\u003C\/div\u003E\n  \u003C\/div\u003E\n\n  \u003Cdiv class=\u0022field field--name-publishers-version field--type-link field--label-visually_hidden field--mode-teaser\u0022\u003E\n    \u003Cdiv class=\u0022field--label sr-only\u0022\u003EPublisher\u0027s Version\u003C\/div\u003E\n              \u003Cdiv class=\u0022field--item\u0022\u003E\u003Ca href=\u0022https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33257679\u0022\u003EPublisher\u0026#039;s Version\u003C\/a\u003E\u003C\/div\u003E\n          \u003C\/div\u003E\n                \u003Cdiv class=\u0022field--label field--abstract\u0022\u003E\n      \u003Cbutton class=\u0022btn-abstract collapsed\u0022 data-toggle=\u0022collapse\u0022 data-target=\u0022#collapseAbstract\u0022 aria-expanded=\u0022false\u0022 aria-controls=\u0022collapseAbstract\u0022\u003EAbstract \u003C\/button\u003E\n    \u003C\/div\u003E\n                  \u003Cdiv class=\u0022field--item abstract--content collapse\u0022 id=\u0022collapseAbstract\u0022 aria-expanded=\u0026quot;false\u0026quot;\u003E\u003Cp\u003EVaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2\u00a0transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2\u00a0transgenic mice produced a modest TH1\/2\/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2\u00a0transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.\u003C\/p\u003E\n\u003C\/div\u003E\n        \n  \u003C\/div\u003E\n\u003C\/article\u003E\n\u003C\/li\u003E\n \u003Cli\u003E\n\u003Carticle class=\u0022bibcite-reference bibcite bibcite--teaser\u0022\u003E\n  \n  \n  \n\n  \u003Cdiv class=\u0022bibcite__content\u0022\u003E\n    \u003Cdiv class=\u0022bibcite-citation\u0022\u003E\n      \u003Cdiv class=\u0022csl-bib-body\u0022\u003E\u003Cdiv class=\u0022csl-entry\u0022\u003ESingh, Dhiraj Kumar, Bindu Singh, Shashank R Ganatra, Michal Gazi, Journey Cole, Rajesh Thippeshappa, Kendra J Alfson, et al. (2021) 2021. \u201c\u003Ca href=\u0022\/lms-lab\/publications\/responses-acute-infection-sars-cov-2-lungs-rhesus-macaques-baboons-and-marmosets\u0022 hreflang=\u0022en\u0022\u003EResponses to Acute Infection With SARS-CoV-2 in the Lungs of Rhesus Macaques, Baboons and Marmosets.\u003C\/a\u003E\u201d. \u003Ci\u003ENature Microbiology\u003C\/i\u003E 6 (1): 73-86. https:\/\/doi.org\/10.1038\/s41564-020-00841-4.\u003C\/div\u003E\u003C\/div\u003E\n  \u003C\/div\u003E\n\n  \u003Cdiv class=\u0022field field--name-publishers-version field--type-link field--label-visually_hidden field--mode-teaser\u0022\u003E\n    \u003Cdiv class=\u0022field--label sr-only\u0022\u003EPublisher\u0027s Version\u003C\/div\u003E\n              \u003Cdiv class=\u0022field--item\u0022\u003E\u003Ca href=\u0022https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33340034\u0022\u003EPublisher\u0026#039;s Version\u003C\/a\u003E\u003C\/div\u003E\n          \u003C\/div\u003E\n                \u003Cdiv class=\u0022field--label field--abstract\u0022\u003E\n      \u003Cbutton class=\u0022btn-abstract collapsed\u0022 data-toggle=\u0022collapse\u0022 data-target=\u0022#collapseAbstract\u0022 aria-expanded=\u0022false\u0022 aria-controls=\u0022collapseAbstract\u0022\u003EAbstract \u003C\/button\u003E\n    \u003C\/div\u003E\n                  \u003Cdiv class=\u0022field--item abstract--content collapse\u0022 id=\u0022collapseAbstract\u0022 aria-expanded=\u0026quot;false\u0026quot;\u003E\u003Cp\u003ENon-human primate models will expedite therapeutics and vaccines for coronavirus disease 2019 (COVID-19) to clinical trials. Here, we compare acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old rhesus macaques, baboons and old marmosets. Macaques had clinical signs of viral infection, mild to moderate pneumonitis and extra-pulmonary pathologies, and both age groups recovered in two weeks. Baboons had prolonged viral RNA shedding and substantially more lung inflammation compared with macaques. Inflammation in bronchoalveolar lavage was increased in old versus young baboons. Using techniques including computed tomography imaging, immunophenotyping, and alveolar\/peripheral cytokine response and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent type-I interferon response. Macaques developed T-cell memory phenotypes\/responses and bystander cytokine production. Old macaques had lower titres of SARS-CoV-2-specific IgG antibody levels compared with young macaques. Acute respiratory distress in macaques and baboons recapitulates the progression of COVID-19 in humans, making them suitable as models to test vaccines and therapies.\u003C\/p\u003E\n\u003C\/div\u003E\n        \n  \u003C\/div\u003E\n\u003C\/article\u003E\n\u003C\/li\u003E\n \u003Cli\u003E\n\u003Carticle class=\u0022bibcite-reference bibcite bibcite--teaser\u0022\u003E\n  \n  \n  \n\n  \u003Cdiv class=\u0022bibcite__content\u0022\u003E\n    \u003Cdiv class=\u0022bibcite-citation\u0022\u003E\n      \u003Cdiv class=\u0022csl-bib-body\u0022\u003E\u003Cdiv class=\u0022csl-entry\u0022\u003EChiem, Kevin, Desarey Morales Vasquez, Jun-Gyu Park, Roy Neal Platt, Tim Anderson, Mark R Walter, James J Kobie, Chengjin Ye, and Luis Martinez-Sobrido. (2021) 2021. \u201c\u003Ca href=\u0022\/lms-lab\/publications\/generation-and-characterization-recombinant-sars-cov-2-expressing-reporter-genes\u0022 hreflang=\u0022en\u0022\u003EGeneration and Characterization of Recombinant SARS-CoV-2 Expressing Reporter Genes.\u003C\/a\u003E\u201d. \u003Ci\u003EJournal of Virology\u003C\/i\u003E 95 (7). https:\/\/doi.org\/10.1128\/JVI.02209-20.\u003C\/div\u003E\u003C\/div\u003E\n  \u003C\/div\u003E\n\n  \u003Cdiv class=\u0022field field--name-publishers-version field--type-link field--label-visually_hidden field--mode-teaser\u0022\u003E\n    \u003Cdiv class=\u0022field--label sr-only\u0022\u003EPublisher\u0027s Version\u003C\/div\u003E\n              \u003Cdiv class=\u0022field--item\u0022\u003E\u003Ca href=\u0022https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/33431557\u0022\u003EPublisher\u0026#039;s Version\u003C\/a\u003E\u003C\/div\u003E\n          \u003C\/div\u003E\n                \u003Cdiv class=\u0022field--label field--abstract\u0022\u003E\n      \u003Cbutton class=\u0022btn-abstract collapsed\u0022 data-toggle=\u0022collapse\u0022 data-target=\u0022#collapseAbstract\u0022 aria-expanded=\u0022false\u0022 aria-controls=\u0022collapseAbstract\u0022\u003EAbstract \u003C\/button\u003E\n    \u003C\/div\u003E\n                  \u003Cdiv class=\u0022field--item abstract--content collapse\u0022 id=\u0022collapseAbstract\u0022 aria-expanded=\u0026quot;false\u0026quot;\u003E\u003Cp\u003EThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible of coronavirus disease 2019 (COVID-19), has devastated public health services and economies worldwide. Despite global efforts to contain the COVID-19 pandemic, SARS-CoV-2 is now found in over 200 countries and has caused an upward death toll of over 1 million human lives as of November 2020. To date, only one Food and Drug Administration (FDA)-approved therapeutic drug (Remdesivir) and a monoclonal antibody, MAb (Bamlanivimab) are available for the treatment of SARS-CoV-2. As with other viruses, studying SARS-CoV-2 requires the use of secondary approaches to detect the presence of the virus in infected cells. To overcome this limitation, we have generated replication-competent recombinant (r)SARS-CoV-2 expressing fluorescent (Venus or mCherry) or bioluminescent (Nluc) reporter genes. Vero E6 cells infected with reporter-expressing rSARS-CoV-2 can be easily detected via fluorescence or luciferase expression and display a good correlation between reporter gene expression and viral replication. Moreover, rSARS-CoV-2 expressing reporter genes have comparable plaque sizes and growth kinetics to those of wild-type virus, rSARS-CoV-2\/WT. We used these reporter-expressing rSARS-CoV-2 to demonstrate their feasibility to identify neutralizing antibodies (NAbs) or antiviral drugs. Our results demonstrate that reporter-expressing rSARS-CoV-2 represent an excellent option to identify therapeutics for the treatment of SARS-CoV-2, where reporter gene expression can be used as valid surrogates to track viral infection. Moreover, the ability to manipulate the viral genome opens the feasibility of generating viruses expressing foreign genes for their use as vaccines for the treatment of SARS-CoV-2 infection.IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), has significantly impacted the human health and economic status worldwide. There is an urgent need to identify effective prophylactics and therapeutics for the treatment of SARS-CoV-2 infection and associated COVID-19 disease. The use of fluorescent- or luciferase-expressing reporter expressing viruses has significantly advanced viral research. Here, we generated recombinant (r)SARS-CoV-2 expressing fluorescent (Venus and mCherry) or luciferase (Nluc) reporter genes and demonstrate that they represent an excellent option to track viral infections \u003Ci\u003Ein vitro.\u003C\/i\u003E Importantly, reporter-expressing rSARS-CoV-2 display similar growth kinetics and plaque phenotype that their wild-type counterpart (rSARS-CoV-2\/WT), demonstrating their feasibility to identify drugs and\/or neutralizing antibodies (NAbs) for the therapeutic treatment of SARS-CoV-2. Henceforth, these reporter-expressing rSARS-CoV-2 can be used to interrogate large libraries of compounds and\/or monoclonal antibodies (MAb), in high-throughput screening settings, to identify those with therapeutic potential against SARS-CoV-2.\u003C\/p\u003E\n\u003C\/div\u003E\n        \n  \u003C\/div\u003E\n\u003C\/article\u003E\n\u003C\/li\u003E\n\u003C\/ul\u003E\n  \u003Cnav role=\u0022navigation\u0022 aria-labelledby=\u0022pagination-for-coronavirus-identify-the-presence-of-the-virus-in-cultured-cells-and-validated-animal-models-of-infection-publications-lop\u0022 id=pager-heading\u003E\n    \u003Ch3 id=\u0022pagination-for-coronavirus-identify-the-presence-of-the-virus-in-cultured-cells-and-validated-animal-models-of-infection-publications-lop\u0022 class=\u0022visually-hidden\u0022\u003Epagination for coronavirus identify the presence of the virus in cultured cells and validated animal models of infection publications lop\u003C\/h3\u003E\n    \u003Cul class=\u0022js-pager__items pager-mini\u0022\u003E\n            \u003Cli class=\u0022current\u0022\u003E\n        \u003Cspan aria-live=\u0022polite\u0022\u003E\n            \u003Cspan class=\u0022visually-hidden\u0022\u003ECoronavirus - Identify the presence of the virus in cultured cells and validated animal models of infection Publications LOP\u003C\/span\u003E\n            1 of 3\n          \u003C\/span\u003E      \u003C\/li\u003E\n              \u003Cli\u003E\n          \u003Ca href=\u0022\/lms-lab\/refresh-widget-content\/2930?page=1\u0026amp;selector=list-of-posts\u0026amp;pagerid=pager-heading\u0026amp;moreid=node-readmore\u0022 class=\u0022use-ajax next\u0022 rel=\u0022next\u0022\u003E\u003Cspan aria-hidden=\u0022true\u0022\u003E\u203a\u203a\u003C\/span\u003E\u003Cspan class=\u0022visually-hidden\u0022\u003ENext page\u003C\/span\u003E\u003C\/a\u003E\n        \u003C\/li\u003E\n          \u003C\/ul\u003E\n  \u003C\/nav\u003E\n\n\u003Cdiv class=\u0022node-readmore\u0022 id=node-readmore\u003E\u003C\/div\u003E\n","settings":null},{"command":"insert","method":"replaceWith","selector":"#","data":"","settings":null},{"command":"insert","method":"replaceWith","selector":"#","data":"","settings":null},{"command":"insert","method":"replaceWith","selector":".field--name-field-widget-title","data":"","settings":null}]