Publicação
Plasmodium berghei/SARS-CoV-2 co-infection phenotype in murine models
| datacite.subject.fos | Departamento de Biologia Vegetal | pt_PT |
| dc.contributor.advisor | Prudêncio, Jorge Miguel Martins | |
| dc.contributor.advisor | Zilhão, Rita, 1959- | |
| dc.contributor.author | Fraga, Ana Catarina Freire | |
| dc.date.accessioned | 2023-09-12T12:13:34Z | |
| dc.date.available | 2024-01-22T01:32:40Z | |
| dc.date.issued | 2023 | |
| dc.date.submitted | 2022 | |
| dc.description | Tese de mestrado, Biologia Molecular e Genética , 2023, Universidade de Lisboa, Faculdade de Ciências | pt_PT |
| dc.description.abstract | Coronavirus disease 2019 (COVID-19) and malaria, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium parasites, respectively, share geographical distribution, in regions where the latter disease is endemic. Because of this geographic overlap, coinfection cases have emerged, albeit with variable clinical presentations, ranging from faster clinical recovery to worse health outcomes. Given the current epidemiologic status of both diseases, the occurrence of co-infections between SARS-CoV-2 and Plasmodium is likely to persist. Thus far, epidemiologic studies and case reports have yielded insufficient data on the reciprocal impact of the two pathogens on either infection and related diseases. As such, an experimental approach of this coinfection is critical for the understanding of how these pathogens interact with each other and the impact of this interaction on the progression of either disease. We established a unique and innovative coinfection model to address this issue experimentally for the first time, employing either transgenic mice expressing SARS-CoV-2’s human receptor for cell invasion – the human angiotensin-converting enzyme 2 (hACE2) – or wild-type mice in combination with human- and mouse-infective variants of SARS-CoV-2, respectively, and the rodent malaria parasite, P. berghei. Our results demonstrate for the first time that an ongoing SARS-CoV-2 infection impacts the outcomes of a subsequent Plasmodium infection. Our data shows that a primary infection by a viral variant that causes a severe disease phenotype leads to an exacerbated anti-viral immune response that markedly impairs a subsequent liver infection by the malaria parasite. Additionally, we demonstrate that a primary infection by a viral variant that causes an attenuated disease phenotype reduces malaria severity in mice subsequently infected with P. berghei, partially protecting these animals from experimental cerebral malaria and increasing their survival. Our results have unveiled a hitherto unknown virus-parasite interaction that could have important epidemiological and clinical repercussions in malaria-endemic regions, particularly regarding the management and control of the diseases caused by both pathogens. This work paves the way for the development of other models of co-infection between Plasmodium and respiratory viruses in relevant in vivo models of disease and we anticipate that it will serve as a steppingstone for further research on coinfections, thus filling an important knowledge gap regarding complex disease presentations. | pt_PT |
| dc.identifier.tid | 203524268 | |
| dc.identifier.uri | http://hdl.handle.net/10451/59225 | |
| dc.language.iso | eng | pt_PT |
| dc.subject | Malária | pt_PT |
| dc.subject | COVID-19 | pt_PT |
| dc.subject | coinfeção | pt_PT |
| dc.subject | Plasmodium | pt_PT |
| dc.subject | SARS-CoV-2 | pt_PT |
| dc.subject | Teses de mestrado - 2023 | pt_PT |
| dc.title | Plasmodium berghei/SARS-CoV-2 co-infection phenotype in murine models | pt_PT |
| dc.type | master thesis | |
| dspace.entity.type | Publication | |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | masterThesis | pt_PT |
| thesis.degree.name | Tese de mestrado em Biologia Molecular e Genética | pt_PT |