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While the platform is potentially cheaper and more scalable than conventional manufacturing systems, expression yields and appropriate post\u2010translational modifications along the plant secretory pathway remain a challenge for certain proteins. Viral fusion glycoproteins in particular are often expressed at low yields in plants and, in some cases, may not be appropriately processed. Recently, however, transiently or stably engineering the host plant has shown promise as a strategy for producing heterologous proteins with more complex maturation requirements. In this study we investigated the co\u2010expression of a suite of human chaperones to improve the production of a human immunodeficiency virus (HIV) type 1 soluble gp140 vaccine candidate in\n                    <jats:italic>Nicotiana benthamiana<\/jats:italic>\n                    plants. The co\u2010expression of calreticulin (CRT) resulted in a dramatic increase in Env expression and ameliorated the endoplasmic reticulum (ER) stress response \u2010 as evidenced by lower transcript abundance of representative stress\u2010responsive genes. The co\u2010expression of CRT similarly improved accumulation of glycoproteins from Epstein\u2010Barr virus (EBV), Rift Valley fever virus (RVFV) and chikungunya virus (CHIKV), suggesting that the endogenous chaperone machinery may impose a bottleneck for their production. We subsequently successfully combined the co\u2010expression of human CRT with the transient expression of human furin, to enable the production of an appropriately cleaved HIV gp140 antigen. These transient plant host engineering strategies are a promising approach for the production of high yields of appropriately processed and cleaved viral glycoproteins.\n                  <\/jats:p>","DOI":"10.1111\/pbi.13369","type":"journal-article","created":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T00:18:59Z","timestamp":1582589939000},"page":"2109-2117","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Co\u2010expression of human calreticulin significantly improves the production of HIV gp140 and other viral glycoproteins in plants"],"prefix":"10.1111","volume":"18","author":[{"given":"Emmanuel","family":"Margolin","sequence":"first","affiliation":[{"name":"Division of Medical Virology Department of Pathology Faculty of Health Sciences University of Cape Town Cape Town South Africa"},{"name":"Wellcome Trust Centre for Infectious Disease Research in Africa University of Cape Town Cape Town South Africa"},{"name":"Faculty of Health Sciences Institute of Infectious Disease and Molecular Medicine University of Cape Town Cape Town South Africa"},{"name":"Biopharming Research Unit Department of Molecular and Cell Biology University of Cape Town Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngjun J.","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Louisville School of Medicine Louisville KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Verbeek","sequence":"additional","affiliation":[{"name":"Biopharming Research Unit Department of Molecular and Cell Biology University of Cape Town Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Naude","sequence":"additional","affiliation":[{"name":"Biopharming Research Unit Department of Molecular and Cell Biology University of Cape Town Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ponndorf","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry John Innes Centre Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia Alexandrovna","family":"Meshcheriakova","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry John Innes Centre Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7808-5089","authenticated-orcid":false,"given":"Hadrien","family":"Peyret","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry John Innes Centre Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel T.","family":"van Diepen","sequence":"additional","affiliation":[{"name":"Division of Medical Virology Department of Pathology Faculty of Health Sciences University of Cape Town Cape Town South Africa"},{"name":"Faculty of Health Sciences Institute of Infectious Disease and Molecular Medicine University of Cape Town Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ros","family":"Chapman","sequence":"additional","affiliation":[{"name":"Division of Medical Virology Department of Pathology Faculty of Health Sciences University of Cape Town Cape Town South Africa"},{"name":"Faculty of Health Sciences Institute of Infectious Disease and Molecular Medicine University of Cape Town Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2116-7913","authenticated-orcid":false,"given":"Ann E.","family":"Meyers","sequence":"additional","affiliation":[{"name":"Biopharming Research Unit Department of Molecular and Cell Biology University of Cape Town Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George Peter","family":"Lomonossoff","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry John Innes Centre Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7231-3004","authenticated-orcid":false,"given":"Nobuyuki","family":"Matoba","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Louisville School of Medicine Louisville KY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna\u2010Lise","family":"Williamson","sequence":"additional","affiliation":[{"name":"Division of Medical Virology Department of Pathology Faculty of Health Sciences University of Cape Town Cape Town South Africa"},{"name":"Wellcome Trust Centre for Infectious Disease Research in Africa University of Cape Town Cape Town South Africa"},{"name":"Faculty of Health Sciences Institute of Infectious Disease and Molecular Medicine University of Cape Town Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8024-9911","authenticated-orcid":false,"given":"Edward P.","family":"Rybicki","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences Institute of Infectious Disease and Molecular Medicine University of Cape Town Cape Town South Africa"},{"name":"Biopharming Research Unit Department of Molecular and Cell Biology University of Cape Town Cape Town South 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