Marcilio Fumagalli

Dr. Marcilio Fumagalli

orcid

Research Focus & Metrics

Academic Career Length

9Years (2018-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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4 September 2020 in Science
Verified
Journal Article
Open access
DCDarlan S. Candido
Darlan S. Candido
ICIngra M. Claro
Ingra M. Claro
JJJaqueline de Jesus
Jaqueline de Jesus
William SouzaWilliam Souza
William Souza
FMFilipe Moreira
Filipe Moreira
NFNuno Rodrigues Faria
Nuno Rodrigues Faria
The spread of SARS-CoV-2 in Brazil: Brazil has been hard-hit by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Candido et al. combined genomic and epidemiological analyses to investigate the impact of nonpharmaceutical interventions (NPIs) in the country. By setting up a network of genomic laboratories using harmonized protocols, the researchers found a 29% positive rate for SARS-CoV-2 among collected samples. More than 100 international introductions of SARS-CoV-2 into Brazil were identified, including three clades introduced from Europe that were already well established before the implementation of NPIs and travel bans. The virus spread from urban centers to the rest of the country, along with a 25% increase in the average distance traveled by air passengers before travel bans, despite an overall drop in short-haul travel. Unfortunately, the evidence confirms that current interventions remain insufficient to keep virus transmission under control in Brazil. Science , this issue p. 1255

3 September 2019 in PLOS Pathogens
Verified
Journal Article
Open access
PDF file
LCLuiza A. de Castro-Jorge
Luiza A. de Castro-Jorge
RCRenan V. H. de Carvalho
Renan V. H. de Carvalho
TKTaline M. Klein
Taline M. Klein
CHCarlos H. Hiroki
Carlos H. Hiroki
ALAlexandre H. Lopes
Alexandre H. Lopes
DZDario S. Zamboni
Dario S. Zamboni
Mayaro virus (MAYV) is an arbovirus that circulates in Latin America and is emerging as a potential threat to public health. Infected individuals develop Mayaro fever, a severe inflammatory disease characterized by high fever, rash, arthralgia, myalgia and headache. The disease is often associated with a prolonged arthralgia mediated by a chronic inflammation that can last months. Although the immune response against other arboviruses, such as chikungunya virus (CHIKV), dengue virus (DENV) and Zika virus (ZIKV), has been extensively studied, little is known about the pathogenesis of MAYV infection. In this study, we established models of MAYV infection in macrophages and in mice and found that MAYV can replicate in bone marrow-derived macrophages and robustly induce expression of inflammasome proteins, such as NLRP3, ASC, AIM2, and Caspase-1 (CASP1). Infection performed in macrophages derived from Nlrp3–/–, Aim2–/–, Asc–/–and Casp1/11–/–mice indicate that the NLRP3, but not AIM2 inflammasome is essential for production of inflammatory cytokines, such as IL-1β. We also determined that MAYV triggers NLRP3 inflammasome activation by inducing reactive oxygen species (ROS) and potassium efflux. In vivo infections performed in inflammasome-deficient mice indicate that NLRP3 is involved with footpad swelling, inflammation and pain, establishing a role of the NLRP3 inflammasome in the MAYV pathogenesis. Accordingly, we detected higher levels of caspase1-p20, IL-1β and IL-18 in the serum of MAYV-infected patients as compared to healthy individuals, supporting the participation of the NLRP3-inflammasome during MAYV infection in humans. Viruses transmitted by mosquitoes have recently received huge attention from the media because the epidemics caused by Zika and chikungunya virus rapidly spread to new areas and infected a large number of individuals. Mayaro is a virus transmitted by mosquitoes that circulates in the Caribbean and tropical regions of Latin America. It causes a highly inflammatory disease, called Mayaro fever, and acute disease is often followed by a prolonged arthralgia mediated by chronic inflammation that can last months or years. The spread of Mayaro to urban areas is a major concern by the authorities, given that the virus has potential to cause an epidemic if spread in high-risk areas. Thus, understanding the mechanisms related to the pathogenesis of this infectious agent would be of great value to treat and prevent the disease. Here, we established an adult mouse model of Mayaro infection and demonstrated that the virus activates the NLRP3 inflammasome, which is important to regulate this viral disease. Our study provides molecular targets for a future treatment of Mayaro fever and provides an experimental model to understand the pathology caused by this emerging viral pathogen.

22 March 2018 in Viruses
Verified
Journal Article
Open access
PDF file
William SouzaWilliam Souza
William Souza
TDTristan Dennis
Tristan Dennis
MFMarcilio Fumagalli
Marcilio Fumagalli
Jansen AraujoJansen Araujo
Jansen Araujo
Gilberto Sabino-SantosGilberto Sabino-Santos
Gilberto Sabino-Santos
Robert James GiffordRobert James Gifford
Robert James Gifford
Parvoviruses (family Parvoviridae) are small, single-stranded DNA viruses. Many parvoviral pathogens of medical, veterinary and ecological importance have been identified. In this study, we used high-throughput sequencing (HTS) to investigate the diversity of parvoviruses infecting wild and domestic animals in Brazil. We identified 21 parvovirus sequences (including twelve nearly complete genomes and nine partial genomes) in samples derived from rodents, bats, opossums, birds and cattle in Pernambuco, São Paulo, Paraná and Rio Grande do Sul states. These sequences were investigated using phylogenetic and distance-based approaches and were thereby classified into eight parvovirus species (six of which have not been described previously), representing six distinct genera in the subfamily Parvovirinae. Our findings extend the known biogeographic range of previously characterized parvovirus species and the known host range of three parvovirus genera (Dependovirus, Aveparvovirus and Tetraparvovirus). Moreover, our investigation provides a window into the ecological dynamics of parvovirus infections in vertebrates, revealing that many parvovirus genera contain well-defined sub-lineages that circulate widely throughout the world within particular taxonomic groups of hosts.

17 August 2022 in Nature Communications
Verified
Journal Article
Open access
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JCJulia T. Castro
Julia T. Castro
PAPatrick Azevedo
Patrick Azevedo
MFMarcilio Fumagalli
Marcilio Fumagalli
NHNatalia S. Hojo-Souza
Natalia S. Hojo-Souza
NSNatalia Salazar
Natalia Salazar
RGRicardo T. Gazzinelli
Ricardo T. Gazzinelli
Both T cells and B cells have been shown to be generated after infection with SARS-CoV-2 yet protocols or experimental models to study one or the other are less common. Here, we generate a chimeric protein (SpiN) that comprises the receptor binding domain (RBD) from Spike (S) and the nucleocapsid (N) antigens from SARS-CoV-2. Memory CD4+ and CD8+ T cells specific for SpiN could be detected in the blood of both individuals vaccinated with Coronavac SARS-CoV-2 vaccine and COVID-19 convalescent donors. In mice, SpiN elicited a strong IFN-γ response by T cells and high levels of antibodies to the inactivated virus, but not detectable neutralizing antibodies (nAbs). Importantly, immunization of Syrian hamsters and the human Angiotensin Convertase Enzyme-2-transgenic (K18-ACE-2) mice with Poly ICLC-adjuvanted SpiN promotes robust resistance to the wild type SARS-CoV-2, as indicated by viral load, lung inflammation, clinical outcome and reduction of lethality. The protection induced by SpiN was ablated by depletion of CD4+ and CD8+ T cells and not transferred by antibodies from vaccinated mice. Finally, vaccination with SpiN also protects the K18-ACE-2 mice against infection with Delta and Omicron SARS-CoV-2 isolates. Hence, vaccine formulations that elicit effector T cells specific for the N and RBD proteins may be used to improve COVID-19 vaccines and potentially circumvent the immune escape by variants of concern.

9 November 2021 in Journal of Virology
Verified
Journal Article
Closed access
MFMarcilio Fumagalli
Marcilio Fumagalli
WSWilliam Marciel de Souza
William Marciel de Souza
LCLuiza Antunes de Castro-Jorge
Luiza Antunes de Castro-Jorge
RCRenan Villanova Homem de Carvalho
Renan Villanova Homem de Carvalho
ÍCÍtalo de Araújo Castro
Ítalo de Araújo Castro
LFLuiz Tadeu Moraes Figueiredo
Luiz Tadeu Moraes Figueiredo
Mosquito-borne viruses have a worldwide impact, especially in tropical climates. Chikungunya virus has been present mostly in developing countries, causing millions of infections, while Mayaro virus, a close relative, has been limited to the Caribbean and tropical regions of Latin America.

23 January 2020 in PLOS Pathogens
Verified
Journal Article
Open access
PDF file
QLQuintin Lee
Quintin Lee
Matthew PadulaMatthew Padula
Matthew Padula
NPNatalia Pinello
Natalia Pinello
SWSimon Williams
Simon Williams
MOMatthew O'Rourke
Matthew O'Rourke
CJChristopher J. Jolly
Christopher J. Jolly
Mouse kidney parvovirus (MKPV) is a member of the provisional genus Chapparvovirus that causes renal disease in immune-compromised mice, with a disease course reminiscent of polyomavirus-associated nephropathy in immune-suppressed kidney transplant patients. Here we map four major MKPV transcripts, created by alternative splicing, to a common initiator region, and use mass spectrometry to identify “p10” and “p15” as novel chapparvovirus accessory proteins produced in MKPV-infected kidneys. p15 and the splicing-dependent putative accessory protein NS2 are conserved in all near-complete amniote chapparvovirus genomes currently available (from mammals, birds and a reptile). In contrast, p10 may be encoded only by viruses with >60% amino acid identity to MKPV. We show that MKPV is kidney-tropic and that the bat chapparvovirus DrPV-1 and a non-human primate chapparvovirus, CKPV, are also found in the kidneys of their hosts. We propose, therefore, that many mammal chapparvoviruses are likely to be nephrotropic. Parvoviruses are small, genetically simple single-strand DNA viruses that remain viable outside their hosts for very long periods of time. They cause disease in several domesticated species and in humans. Mouse kidney parvovirus (MKPV) is a causative agent of kidney failure in immune-compromised mice and is the only member of the provisional Chapparvovirus genus for which the complete genome including telomeres is known. Here, we show that MKPV propagates almost exclusively in the kidneys of mice infected naturally, wherein it produces novel accessory proteins whose coding regions are conserved in amniote-associated chapparvovirus sequences. We assemble a closely related complete viral genome present in DNA extracted from the kidney of a wild Cebus imitator monkey, and show that another related chapparvovirus is preferentially found in kidneys of the vampire bat Desmodus rotundus. We conclude that many mammal-hosted chapparvovirus are adapted to the kidney niche and may therefore cause disease following kidney stress in multiple species.