Pub Date : 2023-01-01DOI: 10.1590/0074-02760220072
Fernanda Pereira Monteiro, Victor de Souza Tavares, Rayane da Silva Oliveira Souza, Larissa Paola Rodrigues Venâncio, Mary Hellen Fabres-Klein, Rodrigo Feliciano do Carmo, Raphael Contelli Klein, Jonilson Berlink Lima, Théo Araújo-Santos
Background: Patients with severe coronavirus disease 2019 (COVID-19) often present with coagulopathies and have high titres of circulating antibodies against viral proteins.
Objectives: Herein, we evaluated the association between D-dimer and circulating immunoglobulin levels against viral proteins in patients at different clinical stages of COVID-19.
Methods: For this, we performed a cross-sectional study involving patients of the first wave of COVID-19 clinically classified as oligosymptomatic (n = 22), severe (n = 30), cured (n = 27) and non-infected (n = 9). Next, we measured in the plasma samples the total and fraction of immunoglobulins against the nucleoprotein (NP) and the receptor-binding domain (RBD) of the spike proteins by enzyme-linked immunosorbent assay (ELISA) assays.
Findings: Patients with severe disease had a coagulation disorder with high levels of D-dimer as well as circulating IgG against the NP but not the RBD compared to other groups of patients. In addition, high levels of D-dimer and IgG against the NP and RBD were associated with disease severity among the patients in this study.
Main conclusions: Our data suggest that IgG against NP and RBD participates in the worsening of COVID-19. Although the humoral response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is partially understood, and more efforts are needed to clarify gaps in the knowledge of this process.
{"title":"Coagulopathy and the humoral response against viral proteins in patients at different stages of COVID-19.","authors":"Fernanda Pereira Monteiro, Victor de Souza Tavares, Rayane da Silva Oliveira Souza, Larissa Paola Rodrigues Venâncio, Mary Hellen Fabres-Klein, Rodrigo Feliciano do Carmo, Raphael Contelli Klein, Jonilson Berlink Lima, Théo Araújo-Santos","doi":"10.1590/0074-02760220072","DOIUrl":"https://doi.org/10.1590/0074-02760220072","url":null,"abstract":"<p><strong>Background: </strong>Patients with severe coronavirus disease 2019 (COVID-19) often present with coagulopathies and have high titres of circulating antibodies against viral proteins.</p><p><strong>Objectives: </strong>Herein, we evaluated the association between D-dimer and circulating immunoglobulin levels against viral proteins in patients at different clinical stages of COVID-19.</p><p><strong>Methods: </strong>For this, we performed a cross-sectional study involving patients of the first wave of COVID-19 clinically classified as oligosymptomatic (n = 22), severe (n = 30), cured (n = 27) and non-infected (n = 9). Next, we measured in the plasma samples the total and fraction of immunoglobulins against the nucleoprotein (NP) and the receptor-binding domain (RBD) of the spike proteins by enzyme-linked immunosorbent assay (ELISA) assays.</p><p><strong>Findings: </strong>Patients with severe disease had a coagulation disorder with high levels of D-dimer as well as circulating IgG against the NP but not the RBD compared to other groups of patients. In addition, high levels of D-dimer and IgG against the NP and RBD were associated with disease severity among the patients in this study.</p><p><strong>Main conclusions: </strong>Our data suggest that IgG against NP and RBD participates in the worsening of COVID-19. Although the humoral response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is partially understood, and more efforts are needed to clarify gaps in the knowledge of this process.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9870257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10592407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1590/0074-02760230088
Lisiane Lappe dos Reis, Lirna Salvioni Silva de Souza, Francisco Carlos de Oliveira Braga, Dayane Costa de Souza Lima, Natália Aparecida de Souza Lima, Jessica da Silva Padinha, Alessandra Ferreira Dales Nava, Ana Carolina Paulo Vicente
BACKGROUND The parasite Giardia duodenalis infects a wide range of vertebrate hosts, including domestic and wild animals as well as humans. Giardia is genotyped into eight assemblages (A-H). Zoonotic assemblages A and B have already been identified in humans and wild and domestic animals (non-human primates and cats) from Brazilian Amazon and in the world. Due to its zoonotic/zooanthroponotic nature, surveillance initiatives and the definition of Giardia assemblages are important in order to characterise the epidemiological scenario and to implement further control measures. OBJECTIVES Determine assemblages of G. duodenalis in sloths from the Brazilian Amazon Region. METHODS Faecal parasitological examination of sloths from Amazonas State. Polymerase chain reaction (PCR) targeting the beta giardin (BG), and genes from multilocus sequence typing (MLST) scheme, amplicon sequencing and phylogenetic analysis. FINDINGS Here, we identified, by microscopy, Giardia in two northern sloths (Bradypus tridactylus). These two samples were submitted to molecular assays and it was revealed that both were infected by G. duodenalis assemblage A. Phylogenetic analysis showed that they belong to assemblage A within sequences from humans and wild and domestic animals. CONCLUSION Therefore, besides showing, by the first time, the current presence of this parasite in sloths, our findings reveals that this wild animal species would be part of the zoonotic/zooanthroponotic scenario of this parasite in the Brazilian Amazon.
{"title":"Zoonotic Giardia duodenalis assemblage A in northern sloth from Brazilian Amazon","authors":"Lisiane Lappe dos Reis, Lirna Salvioni Silva de Souza, Francisco Carlos de Oliveira Braga, Dayane Costa de Souza Lima, Natália Aparecida de Souza Lima, Jessica da Silva Padinha, Alessandra Ferreira Dales Nava, Ana Carolina Paulo Vicente","doi":"10.1590/0074-02760230088","DOIUrl":"https://doi.org/10.1590/0074-02760230088","url":null,"abstract":"BACKGROUND The parasite Giardia duodenalis infects a wide range of vertebrate hosts, including domestic and wild animals as well as humans. Giardia is genotyped into eight assemblages (A-H). Zoonotic assemblages A and B have already been identified in humans and wild and domestic animals (non-human primates and cats) from Brazilian Amazon and in the world. Due to its zoonotic/zooanthroponotic nature, surveillance initiatives and the definition of Giardia assemblages are important in order to characterise the epidemiological scenario and to implement further control measures. OBJECTIVES Determine assemblages of G. duodenalis in sloths from the Brazilian Amazon Region. METHODS Faecal parasitological examination of sloths from Amazonas State. Polymerase chain reaction (PCR) targeting the beta giardin (BG), and genes from multilocus sequence typing (MLST) scheme, amplicon sequencing and phylogenetic analysis. FINDINGS Here, we identified, by microscopy, Giardia in two northern sloths (Bradypus tridactylus). These two samples were submitted to molecular assays and it was revealed that both were infected by G. duodenalis assemblage A. Phylogenetic analysis showed that they belong to assemblage A within sequences from humans and wild and domestic animals. CONCLUSION Therefore, besides showing, by the first time, the current presence of this parasite in sloths, our findings reveals that this wild animal species would be part of the zoonotic/zooanthroponotic scenario of this parasite in the Brazilian Amazon.","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135613434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1590/0074-02760220220
Artur Augusto Velho Mendes Junior, Camila Patrício Braga Filgueira, Luciana de Freitas Campos Miranda, Adilson Benedito de Almeida, Lilian Motta Cantanhêde, Aline Fagundes, Sandro Antônio Pereira, Rodrigo Caldas Menezes, Elisa Cupolillo
Background: Epidemiological data related to leishmaniases or Leishmania infection in horses are scarce. However, studies carried out in different regions in the world showed equids parasitised by Leishmania braziliensis, L. infantum and L. martiniquensis.
Objectives: Identify the Leishmania species causing cutaneous leishmaniasis in a mare, living in Rio de Janeiro State (Brazil), and search the presence of Leishmania viruses in the isolated parasite.
Methods: Isoenzymes and polymerase chain reaction (PCR) targeting ITSrDNA region followed by sequencing were conducted for typing the isolated parasite. A search for Leishmania virus infection was also performed.
Findings: The mare presented skin nodules and ulcers in the left pinna caused by Leishmania spp. that was detected by culture and PCR. The parasite was identified as Leishmania (Mundinia) martiniquensis, infected by Leishbunyavirus (LBV), representing the first description of this species in South America. The animal travelled to different Brazilian regions, but not to outside the country.
Main conclusions: The worldwide distribution of L. martiniquensis and its infection by LBV were confirmed in this study, indicating the autochthonous transmission cycle in Brazil. The clinical profile of the disease in the mare, showing fast spontaneous healing of cutaneous lesions, may indicate that skin lesions related to L. martiniquensis infection in horses might be underdiagnosed.
{"title":"First report of Leishmania (Mundinia) martiniquensis in South American territory and confirmation of Leishbunyavirus infecting this parasite in a mare.","authors":"Artur Augusto Velho Mendes Junior, Camila Patrício Braga Filgueira, Luciana de Freitas Campos Miranda, Adilson Benedito de Almeida, Lilian Motta Cantanhêde, Aline Fagundes, Sandro Antônio Pereira, Rodrigo Caldas Menezes, Elisa Cupolillo","doi":"10.1590/0074-02760220220","DOIUrl":"https://doi.org/10.1590/0074-02760220220","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological data related to leishmaniases or Leishmania infection in horses are scarce. However, studies carried out in different regions in the world showed equids parasitised by Leishmania braziliensis, L. infantum and L. martiniquensis.</p><p><strong>Objectives: </strong>Identify the Leishmania species causing cutaneous leishmaniasis in a mare, living in Rio de Janeiro State (Brazil), and search the presence of Leishmania viruses in the isolated parasite.</p><p><strong>Methods: </strong>Isoenzymes and polymerase chain reaction (PCR) targeting ITSrDNA region followed by sequencing were conducted for typing the isolated parasite. A search for Leishmania virus infection was also performed.</p><p><strong>Findings: </strong>The mare presented skin nodules and ulcers in the left pinna caused by Leishmania spp. that was detected by culture and PCR. The parasite was identified as Leishmania (Mundinia) martiniquensis, infected by Leishbunyavirus (LBV), representing the first description of this species in South America. The animal travelled to different Brazilian regions, but not to outside the country.</p><p><strong>Main conclusions: </strong>The worldwide distribution of L. martiniquensis and its infection by LBV were confirmed in this study, indicating the autochthonous transmission cycle in Brazil. The clinical profile of the disease in the mare, showing fast spontaneous healing of cutaneous lesions, may indicate that skin lesions related to L. martiniquensis infection in horses might be underdiagnosed.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10194060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9543599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1590/0074-02760220144
Adriano José Maia Chaves Filho, Paloma Marinho Jucá, Michelle Verde Ramo Soares, Caio Andrade de Oliveira, Raul Cavalcante de Sousa, Deniele Bezerra Lós, Remo Castro Russo, Juliana Navarro Ueda Yaochite, Danielle S Macedo
Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can infect common mice inducing significant pathological lung lesions and inflammatory responses. This substantially mimics coronavirus disease 19 (COVID-19) infection and pathogenesis in humans.
Objectives: To characterise the effects of recombinant SARS-CoV-2 S1 receptor-binding domain (RBD) peptide in murine macrophage and microglial cells' immune activation compared with classical PAMPs in vitro.
Methods: Murine RAW 264.7 macrophages and BV2 microglial cells were exposed to increasing concentrations of the RBD peptide (0.01, 0.05, and 0.1 µg/mL), Lipopolysaccharide (LPS) and Poly(I:C) and evaluated after two and 24 h for significant markers of macrophage activation. We determined the effects of RBD peptide on cell viability, cleaved caspase 3 expressions, and nuclear morphometry analysis.
Findings: In RAW cells, RBD peptide was cytotoxic, but not for BV2 cells. RAW cells presented increased arginase activity and IL-10 production; however, BV2 cells expressed iNOS and IL-6 after RBD peptide exposure. In addition, RAW cells increased cleaved-caspase-3, apoptosis, and mitotic catastrophe after RBD peptide stimulation but not BV2 cells.
Conclusion: RBD peptide exposure has different effects depending on the cell line, exposure time, and concentration. This study brings new evidence about the immunogenic profile of RBD in macrophage and microglial cells, advancing the understanding of SARS-Cov2 immuno- and neuropathology.
{"title":"In vitro immunogenic profile of recombinant SARS-CoV2 S1-RBD peptide in murine macrophage and microglial cells.","authors":"Adriano José Maia Chaves Filho, Paloma Marinho Jucá, Michelle Verde Ramo Soares, Caio Andrade de Oliveira, Raul Cavalcante de Sousa, Deniele Bezerra Lós, Remo Castro Russo, Juliana Navarro Ueda Yaochite, Danielle S Macedo","doi":"10.1590/0074-02760220144","DOIUrl":"https://doi.org/10.1590/0074-02760220144","url":null,"abstract":"<p><strong>Background: </strong>The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can infect common mice inducing significant pathological lung lesions and inflammatory responses. This substantially mimics coronavirus disease 19 (COVID-19) infection and pathogenesis in humans.</p><p><strong>Objectives: </strong>To characterise the effects of recombinant SARS-CoV-2 S1 receptor-binding domain (RBD) peptide in murine macrophage and microglial cells' immune activation compared with classical PAMPs in vitro.</p><p><strong>Methods: </strong>Murine RAW 264.7 macrophages and BV2 microglial cells were exposed to increasing concentrations of the RBD peptide (0.01, 0.05, and 0.1 µg/mL), Lipopolysaccharide (LPS) and Poly(I:C) and evaluated after two and 24 h for significant markers of macrophage activation. We determined the effects of RBD peptide on cell viability, cleaved caspase 3 expressions, and nuclear morphometry analysis.</p><p><strong>Findings: </strong>In RAW cells, RBD peptide was cytotoxic, but not for BV2 cells. RAW cells presented increased arginase activity and IL-10 production; however, BV2 cells expressed iNOS and IL-6 after RBD peptide exposure. In addition, RAW cells increased cleaved-caspase-3, apoptosis, and mitotic catastrophe after RBD peptide stimulation but not BV2 cells.</p><p><strong>Conclusion: </strong>RBD peptide exposure has different effects depending on the cell line, exposure time, and concentration. This study brings new evidence about the immunogenic profile of RBD in macrophage and microglial cells, advancing the understanding of SARS-Cov2 immuno- and neuropathology.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10065410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9263154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1590/0074-02760220211
Enrique Hector Weir, Jorge Eduardo Rabinovich
Background: Physical factors can determine the level of triatomine abundance, but do not regulate their population densities, and neither do natural enemies.
Objectives: To identify the processes associated with density-dependent triatomine population regulation.
Methods: We set-up a laboratory experiment with four interconnected boxes; the central box harbored Rhodnius prolixus bugs and one hamster. Stage 5 and adult densities of 10, 20, 30, 40, and 60 bugs per hamster, were replicated four times (except the density of 60 bugs). Hamster's irritability and several triatomine responses were measured: feeding, development time and longevity, mortality, fecundity, dispersal, and the net reproductive value (R o ).
Findings: Density had a statistically significant effect on irritability, but not on the percent of bugs feeding. Density was significant on blood meal size ingested in bugs that did not move between boxes, but not significant when the bugs moved. Density and irritability affected the proportion of stage 5 nymphs molting, and the proportion of adult bugs dying per day and over a three-week period. There was a highly significant effect of density and irritability on R o .
Main conclusions: We showed that a density-dependent mechanism, acting through the irritability of the host, seems the most plausible process regulating populations in triatomines.
{"title":"Population size regulation is density-dependent in Rhodnius prolixus (Hemiptera: Reduviidae) through an irritability mechanism.","authors":"Enrique Hector Weir, Jorge Eduardo Rabinovich","doi":"10.1590/0074-02760220211","DOIUrl":"https://doi.org/10.1590/0074-02760220211","url":null,"abstract":"<p><strong>Background: </strong>Physical factors can determine the level of triatomine abundance, but do not regulate their population densities, and neither do natural enemies.</p><p><strong>Objectives: </strong>To identify the processes associated with density-dependent triatomine population regulation.</p><p><strong>Methods: </strong>We set-up a laboratory experiment with four interconnected boxes; the central box harbored Rhodnius prolixus bugs and one hamster. Stage 5 and adult densities of 10, 20, 30, 40, and 60 bugs per hamster, were replicated four times (except the density of 60 bugs). Hamster's irritability and several triatomine responses were measured: feeding, development time and longevity, mortality, fecundity, dispersal, and the net reproductive value (R o ).</p><p><strong>Findings: </strong>Density had a statistically significant effect on irritability, but not on the percent of bugs feeding. Density was significant on blood meal size ingested in bugs that did not move between boxes, but not significant when the bugs moved. Density and irritability affected the proportion of stage 5 nymphs molting, and the proportion of adult bugs dying per day and over a three-week period. There was a highly significant effect of density and irritability on R o .</p><p><strong>Main conclusions: </strong>We showed that a density-dependent mechanism, acting through the irritability of the host, seems the most plausible process regulating populations in triatomines.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9652500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1590/0074-02760220164
Sophia Lincoln Cardoso de Azevedo, Marcos Catanho, Ana Carolina Ramos Guimarães, Teca Calcagno Galvão
Chagas disease is an enduring public health issue in many Latin American countries, receiving insufficient investment in research and development. Strategies for disease control and management currently lack efficient pharmaceuticals, commercial diagnostic kits with improved sensitivity, and vaccines. Genetic heterogeneity of Trypanosoma cruzi is a key aspect for novel drug design since pharmacological technologies rely on the degree of conservation of parasite target proteins. Therefore, there is a need to expand the knowledge regarding parasite genetics which, if fulfilled, could leverage Chagas disease research and development, and improve disease control strategies. The growing capacity of whole-genome sequencing technology and its adoption as disease surveillance routine may be key for solving this long-lasting problem.
{"title":"Genomic surveillance: a potential shortcut for effective Chagas disease management.","authors":"Sophia Lincoln Cardoso de Azevedo, Marcos Catanho, Ana Carolina Ramos Guimarães, Teca Calcagno Galvão","doi":"10.1590/0074-02760220164","DOIUrl":"https://doi.org/10.1590/0074-02760220164","url":null,"abstract":"<p><p>Chagas disease is an enduring public health issue in many Latin American countries, receiving insufficient investment in research and development. Strategies for disease control and management currently lack efficient pharmaceuticals, commercial diagnostic kits with improved sensitivity, and vaccines. Genetic heterogeneity of Trypanosoma cruzi is a key aspect for novel drug design since pharmacological technologies rely on the degree of conservation of parasite target proteins. Therefore, there is a need to expand the knowledge regarding parasite genetics which, if fulfilled, could leverage Chagas disease research and development, and improve disease control strategies. The growing capacity of whole-genome sequencing technology and its adoption as disease surveillance routine may be key for solving this long-lasting problem.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9870261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10601763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1590/0074-02760220109
Gabriela Porto Santos Almeida Silva, Rodrigo Cunha Oliveira, Juliana Sacramento Mota de Souza, Marta Giovanetti, Monick Lindenmeyer Guimarães, Carlos Brites, Joana Paixão Monteiro-Cunha
Background: The human immunodeficiency virus type 1, F1 sub-subtype (HIV-1 F1) circulates in three continents: Africa, Europe, and South America. In Brazil, this sub-subtype co-circulates with subtypes B and C and several recombinant forms, mainly BF1 variants.
Objectives: This study aimed to reconstruct the dynamic history of HIV-1 F1 in Brazil.
Methods: HIV-1 near full-length genome and pol gene nucleotide sequences available in public databases were assembled in two datasets (POL671 and NFLG53) to cover the largest number of F1 sub-subtype sequences. Phylodynamic and temporal analyses were performed.
Findings: Two main strains of the F1 sub-subtype are circulating worldwide. The first (F1.I) was found among Brazilian samples (75%) and the second (F1.II) among Romanian (62%) and other European and African isolates. The F1 subtype epidemic in Brazil originated from a single entry into the country around 1970. This ancestral sample is related to samples isolated in European countries (France, Finland, and Belgium), which are possibly of African origin. Moreover, further migration (1998 CI: 1994-2003) of strains from Brazil to Europe (Spain and the UK) was observed. Interestingly, all different recombinant BF patterns found, even those from outside Brazil, present the same F1 lineage (F1.I) as an ancestor, which could be related to the acquisition of adaptive advantages for the recombinant progenies.
Main conclusions: These findings are important for the understanding of the origin and dynamics of the F1 sub-subtype and a consequent better and greater understanding of the HIV-1 F1 and BF epidemic that still spreads from Brazil to other countries.
{"title":"Tracing the relationship among HIV-1 sub-subtype F1 strains: a phylodynamic perspective.","authors":"Gabriela Porto Santos Almeida Silva, Rodrigo Cunha Oliveira, Juliana Sacramento Mota de Souza, Marta Giovanetti, Monick Lindenmeyer Guimarães, Carlos Brites, Joana Paixão Monteiro-Cunha","doi":"10.1590/0074-02760220109","DOIUrl":"https://doi.org/10.1590/0074-02760220109","url":null,"abstract":"<p><strong>Background: </strong>The human immunodeficiency virus type 1, F1 sub-subtype (HIV-1 F1) circulates in three continents: Africa, Europe, and South America. In Brazil, this sub-subtype co-circulates with subtypes B and C and several recombinant forms, mainly BF1 variants.</p><p><strong>Objectives: </strong>This study aimed to reconstruct the dynamic history of HIV-1 F1 in Brazil.</p><p><strong>Methods: </strong>HIV-1 near full-length genome and pol gene nucleotide sequences available in public databases were assembled in two datasets (POL671 and NFLG53) to cover the largest number of F1 sub-subtype sequences. Phylodynamic and temporal analyses were performed.</p><p><strong>Findings: </strong>Two main strains of the F1 sub-subtype are circulating worldwide. The first (F1.I) was found among Brazilian samples (75%) and the second (F1.II) among Romanian (62%) and other European and African isolates. The F1 subtype epidemic in Brazil originated from a single entry into the country around 1970. This ancestral sample is related to samples isolated in European countries (France, Finland, and Belgium), which are possibly of African origin. Moreover, further migration (1998 CI: 1994-2003) of strains from Brazil to Europe (Spain and the UK) was observed. Interestingly, all different recombinant BF patterns found, even those from outside Brazil, present the same F1 lineage (F1.I) as an ancestor, which could be related to the acquisition of adaptive advantages for the recombinant progenies.</p><p><strong>Main conclusions: </strong>These findings are important for the understanding of the origin and dynamics of the F1 sub-subtype and a consequent better and greater understanding of the HIV-1 F1 and BF epidemic that still spreads from Brazil to other countries.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9870255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10724155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1590/0074-02760220263
María Elisa Vázquez, Andrea Cecilia Mesías, Leonardo Acuña, Joseph Spangler, Brenda Zabala, Cecilia Parodi, Meghna Thakur, Eunkeu Oh, Scott Allan Walper, Cecilia Pérez Brandán
Background: Vaccine development is a laborious craftwork in which at least two main components must be defined: a highly immunogenic antigen and a suitable delivery method. Hence, the interplay of these elements could elicit the required immune response to cope with the targeted pathogen with a long-lasting protective capacity.
Objectives: Here we evaluate the properties of Escherichia coli spherical proteoliposomes - known as outer membrane vesicles (OMVs) - as particles with natural adjuvant capacities and as antigen-carrier structures to assemble an innovative prophylactic vaccine for Chagas disease.
Methods: To achieve this, genetic manipulation was carried out on E. coli using an engineered plasmid containing the Tc24 Trypanosoma cruzi antigen. The goal was to induce the release of OMVs displaying the parasite protein on their surface.
Findings: As a proof of principle, we observed that native OMVs - as well as those carrying the T. cruzi antigen - were able to trigger a slight, but functional humoral response at low immunization doses. Of note, compared to the non-immunized group, native OMVs-vaccinated animals survived the lethal challenge and showed minor parasitemia values, suggesting a possible involvement of innate trained immunity mechanism.
Main conclusion: These results open the range for further research on the design of new carrier strategies focused on innate immunity activation as an additional immunization target and venture to seek for alternative forms in which OMVs could be used for optimizing vaccine development.
{"title":"Exploring the performance of Escherichia coli outer membrane vesicles as a tool for vaccine development against Chagas disease.","authors":"María Elisa Vázquez, Andrea Cecilia Mesías, Leonardo Acuña, Joseph Spangler, Brenda Zabala, Cecilia Parodi, Meghna Thakur, Eunkeu Oh, Scott Allan Walper, Cecilia Pérez Brandán","doi":"10.1590/0074-02760220263","DOIUrl":"https://doi.org/10.1590/0074-02760220263","url":null,"abstract":"<p><strong>Background: </strong>Vaccine development is a laborious craftwork in which at least two main components must be defined: a highly immunogenic antigen and a suitable delivery method. Hence, the interplay of these elements could elicit the required immune response to cope with the targeted pathogen with a long-lasting protective capacity.</p><p><strong>Objectives: </strong>Here we evaluate the properties of Escherichia coli spherical proteoliposomes - known as outer membrane vesicles (OMVs) - as particles with natural adjuvant capacities and as antigen-carrier structures to assemble an innovative prophylactic vaccine for Chagas disease.</p><p><strong>Methods: </strong>To achieve this, genetic manipulation was carried out on E. coli using an engineered plasmid containing the Tc24 Trypanosoma cruzi antigen. The goal was to induce the release of OMVs displaying the parasite protein on their surface.</p><p><strong>Findings: </strong>As a proof of principle, we observed that native OMVs - as well as those carrying the T. cruzi antigen - were able to trigger a slight, but functional humoral response at low immunization doses. Of note, compared to the non-immunized group, native OMVs-vaccinated animals survived the lethal challenge and showed minor parasitemia values, suggesting a possible involvement of innate trained immunity mechanism.</p><p><strong>Main conclusion: </strong>These results open the range for further research on the design of new carrier strategies focused on innate immunity activation as an additional immunization target and venture to seek for alternative forms in which OMVs could be used for optimizing vaccine development.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10207902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9892781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1590/0074-02760230084
Tatiana Prado, Maithê Gaspar Pontes Magalhães, Daniel Andrade Moreira, Martha Lima Brandão, Tulio Machado Fumian, Fernando Cesar Ferreira, Marcia Chame, Luciana Leomil, Wim Maurits Sylvain Degrave, José Paulo Gagliardi Leite, Marize Pereira Miagostovich
Background: Few studies have focused on microbial diversity in indoor environments of ships, as well as the role of the microbiome and its ecological interconnections. In this study, we investigated the microbiome and virome present on the internal surfaces of a polar ship in different stages (beginning, during, and at the end) of the Brazilian Antarctic expedition in order to evaluate abundance of microorganisms in different periods.
Objectives and methods: We used shotgun metagenomic analysis on pooled samples from sampling surfaces in the ship's interior to track the microbial diversity.
Findings: Considering the total fraction of the microbiome, the relative abundance of bacteria, eukaryotes, viruses, and archaea was 83.7%, 16.2%, 0.04%, and 0.002%, respectively. Proteobacteria was the most abundant bacterial phyla, followed by Firmicutes, Actinobacteria, and Bacteroidetes. Concerning the virome, the greatest richness of viral species was identified during the middle of the trip, including ten viral families after de novo assembly: Autographiviridae, Chrysoviridae, Genomoviridae, Herelleviridae, Myoviridae, Partitiviridae, Podoviridae, Potyviridae, Siphoviridae, and Virgaviridae.
Main conclusions: This study contributed to the knowledge of microbial diversity in naval transportation facilities, and variations in the abundance of microorganisms probably occurred due to factors such as the number of passengers and activities on the ship.
{"title":"Microbiome and virome on indoor surfaces of an Antarctic research ship.","authors":"Tatiana Prado, Maithê Gaspar Pontes Magalhães, Daniel Andrade Moreira, Martha Lima Brandão, Tulio Machado Fumian, Fernando Cesar Ferreira, Marcia Chame, Luciana Leomil, Wim Maurits Sylvain Degrave, José Paulo Gagliardi Leite, Marize Pereira Miagostovich","doi":"10.1590/0074-02760230084","DOIUrl":"https://doi.org/10.1590/0074-02760230084","url":null,"abstract":"<p><strong>Background: </strong>Few studies have focused on microbial diversity in indoor environments of ships, as well as the role of the microbiome and its ecological interconnections. In this study, we investigated the microbiome and virome present on the internal surfaces of a polar ship in different stages (beginning, during, and at the end) of the Brazilian Antarctic expedition in order to evaluate abundance of microorganisms in different periods.</p><p><strong>Objectives and methods: </strong>We used shotgun metagenomic analysis on pooled samples from sampling surfaces in the ship's interior to track the microbial diversity.</p><p><strong>Findings: </strong>Considering the total fraction of the microbiome, the relative abundance of bacteria, eukaryotes, viruses, and archaea was 83.7%, 16.2%, 0.04%, and 0.002%, respectively. Proteobacteria was the most abundant bacterial phyla, followed by Firmicutes, Actinobacteria, and Bacteroidetes. Concerning the virome, the greatest richness of viral species was identified during the middle of the trip, including ten viral families after de novo assembly: Autographiviridae, Chrysoviridae, Genomoviridae, Herelleviridae, Myoviridae, Partitiviridae, Podoviridae, Potyviridae, Siphoviridae, and Virgaviridae.</p><p><strong>Main conclusions: </strong>This study contributed to the knowledge of microbial diversity in naval transportation facilities, and variations in the abundance of microorganisms probably occurred due to factors such as the number of passengers and activities on the ship.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10182669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1590/0074-02760230031
Bárbara Figueira Gomes, Mario Roberto Senger, José Teófilo Moreira-Filho, Fabio Jorge de Vasconcellos Junior, Rafael Ferreira Dantas, Raymond Owens, Carolina Horta Andrade, Bruno Junior Neves, Floriano Paes Silva-Junior
Background: Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma, with a limited treatment, mainly based on the use of praziquantel (PZQ). Currently, several aspartic proteases genes have already been identified within the genome of Schistosoma species. At least one enzyme encoded from this gene family (SmAP), named SmCD1, has been validated for the development of schistosomicidal drugs, since it has a key role in haemoglobin digestion by worms.
Objective: In this work, we integrated a structure-based virtual screening campaign, enzymatic assays and adult worms ex vivo experiments aiming to discover the first classes of SmCD1 inhibitors.
Methods: Initially, the 3D-structures of SmCD1, SmCD2 and SmCD3 were generated using homology modelling approach. Using these models, we prioritised 50 compounds from 20,000 compounds from ChemBridge database for further testing in adult worm aqueous extract (AWAE) and recombinant SmCD1 using enzymatic assays.
Findings: Seven compounds were confirmed as hits and among them, two compounds representing new chemical scaffolds, named 5 and 19, had IC50 values against SmCD1 close to 100 μM while presenting binding efficiency indexes comparable to or even higher than pepstatin, a classical tight-binding peptide inhibitor of aspartyl proteases. Upon activity comparison against mammalian enzymes, compound 50 was selective and the most potent against the AWAE aspartic protease activity (IC50 = 77.7 μM). Combination of computational and experimental results indicate that compound 50 is a selective inhibitor of SmCD2. Compounds 5, 19 and 50 tested at low concentrations (10 uM) were neither cytotoxic against WSS-1 cells (48 h) nor could kill adult worms ex-vivo, although compounds 5 and 50 presented a slight decrease on female worms motility on late incubations times (48 or 72 h).
Main conclusion: Overall, the inhibitors identified in this work represent promising hits for further hit-to-lead optimisation.
{"title":"Discovery of new Schistosoma mansoni aspartyl protease inhibitors by structure-based virtual screening.","authors":"Bárbara Figueira Gomes, Mario Roberto Senger, José Teófilo Moreira-Filho, Fabio Jorge de Vasconcellos Junior, Rafael Ferreira Dantas, Raymond Owens, Carolina Horta Andrade, Bruno Junior Neves, Floriano Paes Silva-Junior","doi":"10.1590/0074-02760230031","DOIUrl":"https://doi.org/10.1590/0074-02760230031","url":null,"abstract":"<p><strong>Background: </strong>Schistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma, with a limited treatment, mainly based on the use of praziquantel (PZQ). Currently, several aspartic proteases genes have already been identified within the genome of Schistosoma species. At least one enzyme encoded from this gene family (SmAP), named SmCD1, has been validated for the development of schistosomicidal drugs, since it has a key role in haemoglobin digestion by worms.</p><p><strong>Objective: </strong>In this work, we integrated a structure-based virtual screening campaign, enzymatic assays and adult worms ex vivo experiments aiming to discover the first classes of SmCD1 inhibitors.</p><p><strong>Methods: </strong>Initially, the 3D-structures of SmCD1, SmCD2 and SmCD3 were generated using homology modelling approach. Using these models, we prioritised 50 compounds from 20,000 compounds from ChemBridge database for further testing in adult worm aqueous extract (AWAE) and recombinant SmCD1 using enzymatic assays.</p><p><strong>Findings: </strong>Seven compounds were confirmed as hits and among them, two compounds representing new chemical scaffolds, named 5 and 19, had IC50 values against SmCD1 close to 100 μM while presenting binding efficiency indexes comparable to or even higher than pepstatin, a classical tight-binding peptide inhibitor of aspartyl proteases. Upon activity comparison against mammalian enzymes, compound 50 was selective and the most potent against the AWAE aspartic protease activity (IC50 = 77.7 μM). Combination of computational and experimental results indicate that compound 50 is a selective inhibitor of SmCD2. Compounds 5, 19 and 50 tested at low concentrations (10 uM) were neither cytotoxic against WSS-1 cells (48 h) nor could kill adult worms ex-vivo, although compounds 5 and 50 presented a slight decrease on female worms motility on late incubations times (48 or 72 h).</p><p><strong>Main conclusion: </strong>Overall, the inhibitors identified in this work represent promising hits for further hit-to-lead optimisation.</p>","PeriodicalId":18469,"journal":{"name":"Memorias do Instituto Oswaldo Cruz","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10182670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}