Publications by authors named "Luiz Felipe Leomil Coelho"

32 Publications

Alohomora! What the entry mechanisms tell us about the evolution and diversification of giant viruses and their hosts.

Curr Opin Virol 2021 Apr 26;47:79-85. Epub 2021 Feb 26.

Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, 31270-901, Brasil. Electronic address:

The virosphere is fascinatingly vast and diverse, but as mandatory intracellular parasites, viral particles must reach the intracellular space to guarantee their species' permanence on the planet. While most known viruses that infect animals explore the endocytic pathway to enter the host cell, a diverse group of ancient viruses that make up the phylum Nucleocytoviricota appear to have evolved to explore new access' routes to the cell's cytoplasm. Giant viruses of amoeba take advantage of the phagocytosis process that these organisms exploit a lot, while phycodnavirus must actively break through a algal cellulose cell wall. The mechanisms of entry into the cell and the viruses themselves are diverse, varying in the steps of adhesion, entry, and uncoating. These are clues left by evolution about how these organisms shaped and were shaped by convoluting with eukaryotes.
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http://dx.doi.org/10.1016/j.coviro.2021.02.003DOI Listing
April 2021

Nanoparticles as Vaccines to Prevent Arbovirus Infection: A Long Road Ahead.

Pathogens 2021 Jan 5;10(1). Epub 2021 Jan 5.

Laboratório de Vacinas, Departamento de Microbiologia e Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas 37130-001, Brazil.

Arthropod-borne viruses (arboviruses) are a significant public health problem worldwide. Vaccination is considered one of the most effective ways to control arbovirus diseases in the human population. Nanoparticles have been widely explored as new vaccine platforms. Although nanoparticles' potential to act as new vaccines against infectious diseases has been identified, nanotechnology's impact on developing new vaccines to prevent arboviruses is unclear. Thus, we used a comprehensive bibliographic survey to integrate data concerning the use of diverse nanoparticles as vaccines against medically important arboviruses. Our analysis showed that considerable research had been conducted to develop and evaluate nanovaccines against Chikungunya virus, Dengue virus, Zika virus, Japanese encephalitis virus, and West Nile virus. The main findings indicate that nanoparticles have great potential for use as a new vaccine system against arboviruses. Most of the studies showed an increase in neutralizing antibody production after mouse immunization. Nevertheless, even with significant advances in this field, further efforts are necessary to address the nanoparticles' potential to act as a vaccine against these arboviruses. To promote advances in the field, we proposed a roadmap to help researchers better characterize and evaluate nanovaccines against medically important arboviruses.
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http://dx.doi.org/10.3390/pathogens10010036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824877PMC
January 2021

SARS-CoV-2 mutations and where to find them: an perspective of structural changes and antigenicity of the spike protein.

J Biomol Struct Dyn 2020 Nov 6:1-11. Epub 2020 Nov 6.

Laboratório de Biologia e Tecnologia de Micro-organismos, Departamento de Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Brazil.

Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1844052DOI Listing
November 2020

No effect of prior Dengue virus 1 infection in mouse dams on long-term behavioral profiles in offspring infected with Zika virus during gestation.

Neurosci Lett 2020 11 28;739:135448. Epub 2020 Oct 28.

Federal University of Alfenas, School of Pharmaceutical Sciences, Department of Food and Drugs, Alfenas, MG, CEP: 37130-000, Brazil. Electronic address:

Zika virus (ZIKV) is a mosquito-borne Flavivirus structurally and antigenically related to Dengue virus (DENV). Zika virus has been associated with congenital anomalies and most ZIKV outbreaks have occurred in endemic areas of DENV. The present study investigated the effects of prior DENV serotype 1 (DENV1) immunity in immunocompetent female Swiss mice on gestational ZIKV infection in offspring. Physical/reflex development, locomotor activity, anxiety, visual acuity, and brain-derived neurotrophic factor (BDNF) levels were evaluated in offspring during infancy and adolescence. Anti-DENV1 and anti-ZIKV antibodies were detected in sera of the progenitors, whereas no ZIKV genomes were detected in the offspring brain. Pups from dams with only DENV1 immunity presented alterations of physical/reflex development. Pups from all infected dams exhibited time-related impairments in locomotor activity and anxiolytic-like behavior. Offspring from DENV/ZIKV-infected dams exhibited impairments in visual acuity during infancy but not during adolescence, which was consistent with morphometric analysis of the optic nerve. Pups from DENV1-, ZIKV-, and DENV/ZIKV-infected dams exhibited a decrease in BDNF levels during infancy and an increase during adolescence in distinct brain regions. In summary, we found no influence of prior DENV1 immunity on gestational ZIKV infection in offspring, with the exception of alterations of early visual parameters, and an increase in BDNF levels in the hippocampus during adolescence.
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http://dx.doi.org/10.1016/j.neulet.2020.135448DOI Listing
November 2020

Association of single nucleotide polymorphisms in TNF-α (-308G/A and -238G/A) to dengue: Case-control and meta-analysis study.

Cytokine 2020 10 27;134:155183. Epub 2020 Jul 27.

Laboratório de Biologia de Microrganismos, Universidade Federal do Delta do Parnaíba, Parnaíba, Piauí, Brazil. Electronic address:

Dengue is an acute viral disease whose clinical condition is related to the interaction of factors related to the Dengue virus (DENV), environment and the host, with the immunity of the human host contributing a substantial role in the pathogenesis of DENV infection. Studies have demonstrated that single nucleotide polymorphisms (SNPs) in the promoter regions of cytokine genes such as tumor necrosis factor (TNF-α) affect transcription and/or expression; and therefore, may influence the pathogenesis of infectious diseases, such as dengue. Consequently, the objective of this study was to assess through a case-control study whether there was an association between the presence of SNPs -308G/A and -238G/A in the TNF-α gene and 158 patients with dengue and 123 controls. No association was found between the SNPs and the dengue cases in the study population. We then performed a meta-analysis, retrieving data from case-control studies in the literature for the same polymorphisms. For SNP-308G/A, the GG genotype was associated with dengue fever (DF) risk (OR = 1.24, 1.00-1.53; p = 0.05; I = 0%), while the GA genotype (OR = 0.75, 0.60-0.93; p = 0.01; I = 0%) and allele A (OR = 0.75, 0.60-0.93; p = 0.01; I = 0%) were associated with protection. The genotype GG population in the Asian continent (OR = 1.81 [1.06, 3.09], p = 0.03, I = 0%) and American (OR = 1.29 [1.00, 1.65], p = 0.05, I = 0%) was also associated with protection in the comparison between the cases versus the control group. In each comparison, the dominant model AA + GA (p < 0.00001) conferred protection. For SNP-238G/A the GA genotype was associated with risk for dengue hemorrhagic fever (DHF; OR = 2.17, 1.28-3.67; p = 0.004; I = 0%)), and the dominant AA + GA model (p < 0.00001) was associated with protection in each comparison. In summary, our results did not associate SNPs in the TNF-α gene to dengue in the Brazilian northeast population. However, combined literature data suggested the effect of the GG and GA genotypes of the SNP-308G/A on risk and protection, respectively, in Asian and American populations.
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http://dx.doi.org/10.1016/j.cyto.2020.155183DOI Listing
October 2020

Seroepidemiological survey on sporotrichosis-infection in rural areas of the south of Minas Gerais State, Brazil.

Braz J Microbiol 2021 Mar 13;52(1):41-47. Epub 2020 May 13.

Departamento de Microbiologia e Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, 700 - Centro, Alfenas, Minas Gerais, 37130-001, Brazil.

Sporotrichosis is a subcutaneous mycosis caused by traumatic inoculation into the skin by fungi species of the genus Sporothrix. The disease has different clinical manifestations (cutaneous, lymphocutaneous, and disseminated), and can also progress to a systemic infection. Despite having a worldwide distribution, sporotrichosis is most prevalent in tropical and subtropical countries. In Brazil, reports of the disease are higher frequent, where cases of the disease were found in Rio de Janeiro, Sao Paulo, Curitiba, Pernambuco, and Paraiba, among others. Certain groups of people may be more exposed to the causative agent of disease, such as residents of rural areas. Thus, this work aimed to carry out a seroepidemiological survey of the prevalence of sporotrichosis in four rural locations in the south of Minas Gerais State, Brazil. In this study, we used an indirect ELISA test in the survey on the prevalence of sporotrichosis. Data obtained in this study evaluated a population of 631 individuals and showed a prevalence of 44.69%. The distribution of seroprevalence of sporotrichosis with respect to age groups and gender showed no significant statistical difference. Thus, we found a high seroprevalence of sporotrichosis-infection in rural regions of southern Minas Gerais State, Brazil, with no difference in prevalence in relation to gender and age.
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http://dx.doi.org/10.1007/s42770-020-00279-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966674PMC
March 2021

An in silico integrative protocol for identifying key genes and pathways useful to understand emerging virus disease pathogenesis.

Virus Res 2020 07 24;284:197986. Epub 2020 Apr 24.

Laboratório de Vacinas, Instituto de Ciências Biomédicas, Departamento de Microbiologia e Imunologia, Universidade Federal de Alfenas, Alfenas, Minas Gerais, Brazil. Electronic address:

The pathogenesis of an emerging virus disease is a difficult task due to lack of scientific data about the emerging virus during outbreak threats. Several biological aspects should be studied faster, such as virus replication and dissemination, immune responses to this emerging virus on susceptible host and specially the virus pathogenesis. Integrative in silico transcriptome analysis is a promising approach for understanding biological events in complex diseases. In this study, we propose an in silico protocol for identifying key genes and pathways useful to understand emerging virus disease pathogenesis. To validate our protocol, the emerging arbovirus Zika virus (ZIKV) was chosen as a target micro-organism. First, an integrative transcriptome data from neural cells infected with ZIKV was used to identify shared differentially expressed genes (DEGs). The DEGs were used to identify the potential candidate genes and pathways in ZIKV pathogenesis through gene enrichment analysis and protein‑protein interaction network construction. Thirty DEGs (24 upregulated and 6 downregulated) were identified in all ZIKV-infected cells, primarily associated with endoplasmic reticulum stress and DNA replication pathways. Some of these genes and pathways had biological functions linked to neurogenesis and/or apoptosis, confirming the potential of this protocol to find key genes and pathways involved on disease pathogenesis. Moreover, the proposed in silico protocol performed anintegrated analysis that is able to predict and identify putative biomarkers from different transcriptome data. These biomarkers could be useful to understand virus disease pathogenesis and also help the identification of candidate antiviral drugs.
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http://dx.doi.org/10.1016/j.virusres.2020.197986DOI Listing
July 2020

Virus goes viral: an educational kit for virology classes.

Virol J 2020 01 31;17(1):13. Epub 2020 Jan 31.

Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, 31270-901, Brazil.

Background: Viruses are the most numerous entities on Earth and have also been central to many episodes in the history of humankind. As the study of viruses progresses further and further, there are several limitations in transferring this knowledge to undergraduate and high school students. This deficiency is due to the difficulty in designing hands-on lessons that allow students to better absorb content, given limited financial resources and facilities, as well as the difficulty of exploiting viral particles, due to their small dimensions. The development of tools for teaching virology is important to encourage educators to expand on the covered topics and connect them to recent findings. Discoveries, such as giant DNA viruses, have provided an opportunity to explore aspects of viral particles in ways never seen before. Coupling these novel findings with techniques already explored by classical virology, including visualization of cytopathic effects on permissive cells, may represent a new way for teaching virology. This work aimed to develop a slide microscope kit that explores giant virus particles and some aspects of animal virus interaction with cell lines, with the goal of providing an innovative approach to virology teaching.

Methods: Slides were produced by staining, with crystal violet, purified giant viruses and BSC-40 and Vero cells infected with viruses of the genera Orthopoxvirus, Flavivirus, and Alphavirus. Slides with amoebae infected with different species of giant viruses and stained with hemacolor reagents were also produced.

Results: Staining of the giant viruses allowed better visualization of the viral particles, and this technique highlights the diversity in morphology and sizes among them. Hemacolor staining enabled visualization of viral factories in amoebae, and the staining of infected BSC-40 and Vero cell monolayers with crystal violet highlights plaque-forming units.

Conclusions: This kit was used in practical virology classes for the Biological Sciences course (UFMG, Brazil), and it will soon be made available at a low-cost for elementary school teachers in institutions that have microscopes. We hope this tool will foster an inspiring learning environment.
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http://dx.doi.org/10.1186/s12985-020-1291-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995199PMC
January 2020

Correction to: Effects of metaperiodate and urea solutions on the serological diagnosis of human sporotrichosis using an indirect ELISA test.

Braz J Microbiol 2019 04;50(2):579

Departamento de Microbiologia e Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, 700 - Centro, Alfenas, MG, CEP 37130-001, Brazil.

In the article mentioned above an author's name was misspelled. The correct author name reads as follows: Leila Maria Lopes-Bezerra. We apologize for the inconvenience.
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http://dx.doi.org/10.1007/s42770-019-00070-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863336PMC
April 2019

Effects of metaperiodate and urea solutions on the serological diagnosis of human sporotrichosis using an indirect ELISA test.

Braz J Microbiol 2019 01 13;50(1):139-145. Epub 2018 Dec 13.

Departamento de Microbiologia e Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, 700 - Centro, Alfenas, MG, CEP 37130-001, Brazil.

Sporotrichosis is an infection of the skin caused by traumatic inoculation of the fungus Sporothrix schenckii. Definitive diagnosis relies on direct visualization of the fungus or its isolation on culture medium, although both have low sensitivity. Alternatively, the detection of the antibody response offers a more rapid alternative for diagnosis. Although the available immunoassays possess good sensitivity and specificity, cross-reactivity is still a problem. This study aimed to evaluate the effect of sodium metaperiodate and 6 M urea solutions on the serological diagnosis of sporotrichosis using an enzyme-linked immunosorbent assay (ELISA) test. Ninety-six-well plates were sensitized with exoantigens from the yeast phase of S. schenckii. Sera of patients with confirmed sporotrichosis, sera of patients with paracoccidioidomycosis, and sera of individuals with a sporotrichin-negative skin test were tested. Two strategies were used; the first consisted of treating the antigen with sodium metaperiodate solution for different incubation times, and the second consisted of treating the serum with 6 M urea solution for different incubation times. ROC curve analysis revealed that the best discrimination parameters were obtained using 6 M urea solution incubated for 5 min and serum dilution at 1/600. The use of 6 M urea solution improves the performance of the ELISA test in the diagnosis of sporotrichosis.
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http://dx.doi.org/10.1007/s42770-018-0005-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6863317PMC
January 2019

DC-SIGN and VDR polymorphisms are associated with chronic form of paracoccidioidomycosis with oral manifestations.

Mycoses 2019 Feb 19;62(2):186-192. Epub 2018 Nov 19.

Departamento de Microbiologia e Imunologia, Universidade Federal de Alfenas, Alfenas, MG, Brazil.

Paracoccidioidomycosis (PCM) is a granulomatous disease caused by fungi of the species complex of the Paracoccidioides genus. One of the main clinical manifestations of PCM is the presence of oral lesions with the presence of epithelioid granulomas. In this work, we aimed to evaluate the frequency of SNPs in the TNF-α, JAK1, VDR, DC-SIGN and FcγRIIa genes in patients with chronic PCM and verify possible association of these SNPs with the organisation pattern of the granulomas in the oral lesions. A total of 66 samples of DNA were obtained from oral lesions biopsies and 106 DNA samples were obtained from healthy individuals. The individuals were genotyped for SNPs in DC-SIGN (rs4804803), FcγRIIa (rs1801274), JAK1 (rs11208534), TNF-α (rs1800629) and VDR (rs7975232) by real-time PCR and allele discrimination method. Granulomas were classified as loose or dense according to the histological pattern. In the VDR (rs7975232), the CC genotype (P < 0.001, OR = 5.94, 95% CI = 2.07-17.05), and the C allele (P = 0.027, OR = 2.71, 95% CI = 1.07-6.86), as well as the GG genotype in DC-SIGN (rs4804803) (P = 0.032, OR: 3.76, 95%, I = 1.06-13.38) are associated with an increased risk of oral PCM. Our data indicate that VDR and DC-SIGN genetics variations are related to the susceptibility of oral PCM in the group of patients analysed.
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http://dx.doi.org/10.1111/myc.12866DOI Listing
February 2019

Bovine serum albumin nanoparticles induce histopathological changes and inflammatory cell recruitment in the skin of treated mice.

Biomed Pharmacother 2018 Nov 29;107:1311-1317. Epub 2018 Aug 29.

Institute of Biomedical Sciences, Department of Microbiology and Immunology, Federal University of Alfenas, Minas Gerais, Brazil. Electronic address:

Albumin is a natural, biocompatible, biodegradable and nontoxic polymer and due to these features, nanoparticles made of albumin are a good system for drug or antigen delivery. Polymeric nanoparticles are being widely explored as new vaccines platforms due to the capacity of those nanoparticles to prime the immune system by providing sustained release of the antigen after injection. Biodegradable nanoparticles associated with proteins represent a promising method for in vivo delivery of vaccines. In our previous studies, bovine serum albumin nanoparticles (BSA-NPs) were identified as a promising system for in vivo delivery of microbial antigens. The aim of this work was to show the effect of BSA-NPs on skin after nanoparticles administration. The pro-inflammatory activity of BSA-NPs was evaluated using in vivo models. BSA-NPs are easily uptake by macrophagic RAW 264.7 and BHK-21 cells without any significant cytotoxicity. Histological examination of skin sections from BSA-NPs-treated mice revealed intense cellular infiltration, increased skin thickness, follicular hypertrophy, vascular congestion and marked collagenesis. Mice immunized with recombinant non-structural protein 1 (rNS1) from Dengue virus 1 and BSA-NPs showed a high seroconversion rate if compared to animals immunized only with rNS1. Therefore, the effect of BSA-NPs on skin after BSA-NPs administration has a biotechnological relevance to the rational design of vaccine formulations based on albumin nanocarriers. However in the next years future studies should be carried out to best characterize the effect of BSA-NPs on dendritic cells and establish the role of these nanoparticles as a new vaccine platform for infectious diseases or cancer.
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http://dx.doi.org/10.1016/j.biopha.2018.08.106DOI Listing
November 2018

Serum albumin nanoparticles vaccine provides protection against a lethal Pseudomonas aeruginosa challenge.

Vaccine 2018 10 15;36(43):6408-6415. Epub 2018 Sep 15.

Institute of Biomedical Sciences, Department of Microbiology and Immunology, Federal University of Alfenas, Minas Gerais, Brazil. Electronic address:

Pseudomonas aeruginosa is an opportunistic pathogen that causes severe infections in immunocompromised individuals and in patients with cystic fibrosis. A range of vaccines to prevent infections caused by P. aeruginosa has already been tested, yet no vaccine against this pathogen is currently available. The goal of this study was to evaluate the potential of bovine serum albumin nanoparticles (BSA-NPs) associated with total P. aeruginosa ATCC 27853 antigens in inducing protection against the infection with virulent P. aeruginosa PA14 strain in murine model of nasal infection. Swiss mice were immunized with BSA-NPs associated with total P. aeruginosa antigens (NPPa) or empty NPs (NPe). As positive and negative control, groups of animals were immunized with total antigens of P. aeruginosa ATCC 27853 and phosphate buffered saline, respectively. Immunized mice were infected via nasal route using P. aeruginosa PA14 strain. The survival after 48 h was evaluated and the lungs from animals were processed for quantification of bacterial load, cytokine expression and histopathological analysis. After infection with P. aeruginosa PA14, animals immunized with NPPa had the highest survival rate, the lowest bacterial lung load, a controlled production of cytokines and few histopathological changes. These results indicate that NPPa immunization protected mice from infection, contributing for the elimination of the bacteria from the lungs, which consequently reflected the survival of the animals. Therefore, this vaccine was able to induce a functional response in an animal model of lethal infection and thereby is a promising platform for P. aeruginosa vaccines.
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http://dx.doi.org/10.1016/j.vaccine.2018.08.070DOI Listing
October 2018

Synthesis, activity, and docking studies of eugenol-based glucosides as new agents against Candida sp.

Chem Biol Drug Des 2018 08 18;92(2):1514-1524. Epub 2018 May 18.

Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Alfenas, MG, Brazil.

Seventeen new synthetic derivatives of eugenol (6, 8-15 and 8'-15') were planned following literature reports on antifungal activities of nitroeugenol and eugenol glucoside. The anti-Candida activity of these compounds was investigated by in vitro assay, and the cytotoxicity evaluation was performed with the most active compounds. The peracetylated glucosides presented better biological results than their hydroxylated analogues. The glucoside 11, a 4-nitrobenzamide, showed the best potency (MIC range 11.0-151.84 μm), the wider spectrum of action, and overall the best selectivity indexes, especially against C. tropicalis (~30) and C. krusei (~15). To investigate its possible mechanism of action, glucoside 11 was subjected to molecular docking studies with Candida sp. enzymes involved in ergosterol biosynthesis. Results have shown that the peracetyl glucosyl moiety and the 4-nitrobenzamide group in 11 are effectively involved in its high affinity with the active site of squalene epoxidase.
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http://dx.doi.org/10.1111/cbdd.13318DOI Listing
August 2018

High prevalence of dengue antibodies and the arginine variant of the FcγRIIa polymorphism in asymptomatic individuals in a population of Minas Gerais State, Southeast Brazil.

Immunogenetics 2018 06 21;70(6):355-362. Epub 2017 Nov 21.

Laboratório de Vacinas, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Rua Gabriel Monteiro, 700 Centro, Alfenas, Minas Gerais, 37130-000, Brazil.

Dengue is the most prevalent arthropod-borne viral illness in humans worldwide. Single-nucleotide polymorphisms (SNPs) in genes involved in the immune response, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), IgG Fc receptor II-A (FcγRIIa), vitamin D receptor (VDR), and tumor necrosis factor alpha (TNF-α), were previously reported to be associated with susceptibility to dengue disease in different human populations. Therefore, due to the relevant association of host immune and genetic status with disease susceptibility/severity of dengue, this work aims to verify the frequency of anti-dengue virus antibodies and some dengue-associated risk SNPs in a population in Minas Gerais State, Southeast Brazil. A total of 1560 individuals were genotyped for polymorphisms in DC-SIGN (rs4804803), FcγRIIa (rs1801274), VDR (rs7975232), and TNF-α (rs1800629). The presence of anti-dengue antibodies (IgM and/or IgG) in these samples was also assayed. Anti-dengue antibodies were detected at an overall frequency of 16.86%, indicating a virus infection in asymptomatic individuals. The genotypic frequencies of all SNPs studied did not differ between the asymptomatic and control groups. Regarding the allelic frequencies of the four SNPs analyzed, a higher frequency was detected of the G allele of FcγRIIa/rs1801274 in the asymptomatic individuals when compared to that in the control group (p = 0.03). Therefore, the results showed a high prevalence of asymptomatic individuals in Minas Gerais State, with a potential association between the presence of the G allele of FcγRIIa/rs1801274 and protection against symptomatic disease.
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http://dx.doi.org/10.1007/s00251-017-1046-yDOI Listing
June 2018

In vitro evaluation of the schistosomicidal effect of the extracts, fractions and major 3-hydroxy-2,6-dialkyl-substituted piperidine alkaloids from the flowers of Senna spectabilis (Fabaceae).

Bioorg Med Chem Lett 2016 09 25;26(17):4197-204. Epub 2016 Jul 25.

Universidade Federal de Alfenas Minas Gerais, Alfenas 37130-000, Brazil. Electronic address:

In this work, we present the in vitro schistosomicidal activity evaluation of the most active dichloromethane fraction (FDm) (ED50=83.5μg/mL) and of a mixture of the major alkaloids ((-)-cassine/(-)-spectaline, C/E) (ED50=37.4μg/mL) from the flowers of Senna spectabilis against adult worms and cercariae. We also demonstrate other toxic effects including paralysis of the adult worms, inhibition of the secretory activity, tegument lesions and cercaricidal activity. In the association test of Praziquantel (PZQ)-C/E, we observed up to 80% mortality of Schistosoma mansoni in comparison to PZQ monotherapy. Due to the diversity of the toxic effects, the schistosomicidal activity of C/E is likely a result of a multitarget mechanism involving the tegument, secretory system and neuromotor action.
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http://dx.doi.org/10.1016/j.bmcl.2016.07.058DOI Listing
September 2016

Phylogenetic analysis of Dengue virus 1 isolated from South Minas Gerais, Brazil.

Braz J Microbiol 2016 Jan-Mar;47(1):251-8. Epub 2016 Jan 27.

Laboratório de Virologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil. Electronic address:

Dengue is a major worldwide public health problem, especially in the tropical and subtropical regions of the world. Primary infection with a single Dengue virus serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients who experience secondary infection with a different serotype can progress to a more severe form of the disease, called dengue hemorrhagic fever. The four Dengue virus serotypes (1-4) are antigenically and genetically distinct and each serotype is composed of multiple genotypes. In this study we isolated one Dengue virus 1 serotype, named BR/Alfenas/2012, from a patient with dengue hemorrhagic fever in Alfenas, South Minas Gerais, Brazil and molecular identification was performed based on the analysis of NS5 gene. Swiss mice were infected with this isolate to verify its potential to induce histopathological alterations characteristic of dengue. Liver histopathological analysis of infected animals showed the presence of inflammatory infiltrates, hepatic steatosis, as well as edema, hemorrhage and necrosis focal points. Phylogenetic and evolutionary analyses based on the envelope gene provided evidence that the isolate BR/Alfenas/2012 belongs to genotype V, lineage I and it is probably derived from isolates of Rio de Janeiro, Brazil. The isolate BR/Alfenas/2012 showed two unique amino acids substitutions (SER222THRE and PHE306SER) when compared to other Brazilian isolates from the same genotype/lineage. Molecular models were generated for the envelope protein indicating that the amino acid alteration PHE 306 SER could contribute to a different folding in this region located within the domain III. Further genetic and animal model studies using BR/Alfenas/2012 and other isolates belonging to the same lineage/genotype could help determine the relation of these genetic alterations and dengue hemorrhagic fever in a susceptible population.
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http://dx.doi.org/10.1016/j.bjm.2015.11.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827697PMC
November 2016

Demethylation profile of the TNF-α promoter gene is associated with high expression of this cytokine in Dengue virus patients.

J Med Virol 2016 08 2;88(8):1297-302. Epub 2016 Feb 2.

Laboratório de Vacinas, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, Minas Gerais, Brazil.

Dengue is the most prevalent arthropod-borne viral illness in humans. The overexpression of cytokines by Dengue virus (DENV) infected cells is associated with the most severe forms of the disease. Unmethylated CpG islands are related to a transcriptionally active structure, whereas methylated DNA recruits methyl-binding proteins that inhibit gene expression. Several studies have described the importance of epigenetic events in the regulation and expression of many cytokines. The purpose of the present study was to evaluate the methylation status of the IFN-γ and TNF-α promoters in DNA extracted from dengue infected patients using methylation-specific polymerase chain reaction. A high frequency of demethylation was observed in the TNF-α promoter of DENV infected patients when compared to non-infected controls. The patients with an unmethylated profile showed higher expression of TNF-α mRNA than patients with the methylated status. No difference was found in the methylation frequency between the two analyzed groups regarding the IFN-γ promoter or in the expression of IFN-γ transcripts. The present study provides the first association of TNF-α promoter demethylation in DENV infected individuals and demonstrates a correlation between the methylation status of the region analyzed and the expression of TNF-α transcripts in DENV infected patients. J. Med. Virol. 88:1297-1302, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24478DOI Listing
August 2016

New Eugenol Glucoside-based Derivative Shows Fungistatic and Fungicidal Activity against Opportunistic Candida glabrata.

Chem Biol Drug Des 2016 Jan 31;87(1):83-90. Epub 2015 Aug 31.

Instituto de Química, Universidade Federal de Alfenas, Rua Gabriel Monteiro da Silva, 700 Alfenas, Brazil.

A new series of glucosides modified in their saccharide units were synthesized, evaluated against Candida sp., and compared to prototype 1, an eugenol tetracetyl glucoside previously synthesized and shown to be active against Candida glabrata. Among the new glucosides, benzyl derivative 5 was the most promising, showing fungistatic activity at IC50 18.1 μm against Candida glabrata (threefold higher than fluconazole) and fungicidal activity with a low IC90 value of 36.2 μm. Moreover, the cytotoxic activity of compound 5 (CC50 : 580.9 μm), tested in peripheral blood mononuclear cells, suggests its potential as an agent to treat Candida glabrata infections, with a selectivity index of 32. The new eugenol glucoside 5 may be considered as a novel structural pattern in the development of new anti-Candida drugs.
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http://dx.doi.org/10.1111/cbdd.12625DOI Listing
January 2016

Synthesis and antimicrobial activity of 6-triazolo-6-deoxy eugenol glucosides.

Carbohydr Res 2015 Jun 13;410:1-8. Epub 2015 Apr 13.

Instituto de Química, Universidade Federal de Alfenas, 37130-000, MG, Brazil. Electronic address:

A new series of 1,2,3-triazole eugenol glucosides were synthesized. The new compound structures were confirmed by MS, (1)H NMR and (13)C NMR. All of the synthesized compounds were screened for antimicrobial and cytotoxic activity. Five compounds exerted significant activity against the Gram-negative bacteria Salmonella typhimurium with low IC50 values (49.73-68.53 μΜ), and seven compounds were active against the Gram-positive bacteria Micrococcus luteus (42.89-210.94 μM). In vitro cytotoxicity on mouse spleen cells was also evaluated. One compound bearing a phenyl substituent at the triazole ring showed good activity against Salmonella typhimurium (49.73 μM) and low toxicity to normal cells (CC50=157.83 μM). Thus, the compounds herein can be considered for further modification for improving their antibacterial activity or obtaining novel antibacterial drug candidates.
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http://dx.doi.org/10.1016/j.carres.2015.04.002DOI Listing
June 2015

Genes that encodes NAGT, MIF1 and MIF2 are not virulence factors for kala-azar caused by Leishmania infantum.

Rev Soc Bras Med Trop 2014 Sep-Oct;47(5):593-8

Laboratório de Leishmanioses, Instituto de Doenças Tropicais Natan Portella, Universidade Federal do Piauí, Teresina, PI, Brasil.

Introduction: Kala-azar is a disease resulting from infection by Leishmania donovani and Leishmania infantum. Most patients with the disease exhibit prolonged fever, wasting, anemia and hepatosplenomegaly without complications. However, some patients develop severe disease with hemorrhagic manifestations, bacterial infections, jaundice, and edema dyspnea, among other symptoms, followed by death. Among the parasite molecules that might influence the disease severity are the macrophage migration inhibitory factor-like proteins (MIF1 and MIF2) and N-acetylglucosamine-1-phosphotransferase (NAGT), which act in the first step of protein N-glycosylation. This study aimed to determine whether MIF1, MIF2 and NAGT are virulence factors for severe kala-azar.

Methods: To determine the parasite genotype in kala-azar patients from Northeastern Brazil, we sequenced the NAGT genes of L. infantum from 68 patients as well as the MIF1 and MIF2 genes from 76 different subjects with diverse clinical manifestations. After polymerase chain reaction (PCR), the fragments were sequenced, followed by polymorphism identification.

Results: The nucleotide sequencing of the 144 amplicons revealed the absence of genetic variability of the NAGT, MIF1 and MIF2 genes between the isolates. The conservation of these genes suggests that the clinical variability of kala-azar does not depend upon these genes. Additionally, this conservation suggests that these genes may be critical for parasite survival.

Conclusions: NAGT, MIF1 and MIF2 do not alter the severity of kala-azar. NAGT, MIF1 and MIF2 are highly conserved among different isolates of identical species and exhibit potential for use in phylogenetic inferences or molecular diagnosis.
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http://dx.doi.org/10.1590/0037-8682-0183-2014DOI Listing
July 2015

Dengue virus 2 American-Asian genotype identified during the 2006/2007 outbreak in Piauí, Brazil reveals a Caribbean route of introduction and dissemination of dengue virus in Brazil.

PLoS One 2014 15;9(8):e104516. Epub 2014 Aug 15.

Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Dengue virus (DENV) is the most widespread arthropod-borne virus, and the number and severity of outbreaks has increased worldwide in recent decades. Dengue is caused by DENV-1, DENV- 2, DENV-3 and DENV-4 which are genetically distant. The species has been subdivided into genotypes based on phylogenetic studies. DENV-2, which was isolated from dengue fever patients during an outbreak in Piaui, Brazil in 2006/2007 was analyzed by sequencing the envelope (E) gene. The results indicated a high similarity among the isolated viruses, as well as to other DENV-2 from Brazil, Central America and South America. A phylogenetic and phylogeographic analysis based on DENV-2E gene sequences revealed that these viruses are grouped together with viruses of the American-Asian genotype in two distinct lineages. Our results demonstrate the co-circulation of two American-Asian genotype lineages in northeast Brazil. Moreover, we reveal that DENV-2 lineage 2 was detected in Piauí before it disseminated to other Brazilian states and South American countries, indicating the existence of a new dissemination route that has not been previously described.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104516PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134198PMC
February 2016

Prevalence of paracoccidioidomycosis infection by intradermal reaction in rural areas in Alfenas, Minas Gerais, Brazil.

Rev Inst Med Trop Sao Paulo 2014 Jul-Aug;56(4):281-5

Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, MG, Brazil.

This study aimed to estimate the prevalence of paracoccidioidal infection by intradermal reaction (Delayed-Type Hypersensitivity, DTH) to Paracoccidioides brasiliensis in rural areas in Alfenas, Southern Minas Gerais (MG) State, Brazil, and to assess risk factors (gender, occupation, age, alcohol intake and smoking) associated with infection. We conducted a population-based cross-sectional study using intradermal tests with gp 43 paracoccidioidin in 542 participants, who were previously contacted by local health agents and so spontaneously attended the test. Participants underwent an interview by filling out a registration form with epidemiological data and were tested with an intradermal administration of 0.1 mL of paracoccidioidin in the left forearm. The test was read 48 hours after injection and was considered positive if induration was greater than or equal to 5 mm. Out of 542 participants, 46.67% were positive to the skin test. Prevalence increased in accordance with an increase of age. There was statistical significance only for males. Occupation, alcohol intake and smoking habits were not significantly associated with the risk of paracoccidioidomycosis infection. There is relevance of paracoccidioidomycosis infection in such rural areas, which suggests that further epidemiological and clinical studies on this mycosis should be done in the southern part of Minas Gerais State.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131811PMC
http://dx.doi.org/10.1590/s0036-46652014000400002DOI Listing
October 2014

Identification of blood meal sources of Lutzomyia longipalpis using polymerase chain reaction-restriction fragment length polymorphism analysis of the cytochrome B gene.

Mem Inst Oswaldo Cruz 2014 Jun 7;109(3):379-83. Epub 2014 May 7.

Laboratório de Pesquisas em Leishmanioses, Departamento de Medicina Comunitária, Instituto de Doenças Tropicais Natan Portela, Universidade Federal do Piauí, Teresina, PI, Brasil.

An analysis of the dietary content of haematophagous insects can provide important information about the transmission networks of certain zoonoses. The present study evaluated the potential of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the mitochondrial cytochrome B (cytb) gene to differentiate between vertebrate species that were identified as possible sources of sandfly meals. The complete cytb gene sequences of 11 vertebrate species available in the National Center for Biotechnology Information database were digested with Aci I, Alu I, Hae III and Rsa I restriction enzymes in silico using Restriction Mapper software. The cytb gene fragment (358 bp) was amplified from tissue samples of vertebrate species and the dietary contents of sandflies and digested with restriction enzymes. Vertebrate species presented a restriction fragment profile that differed from that of other species, with the exception of Canis familiaris and Cerdocyon thous. The 358 bp fragment was identified in 76 sandflies. Of these, 10 were evaluated using the restriction enzymes and the food sources were predicted for four: Homo sapiens (1), Bos taurus (1) and Equus caballus (2). Thus, the PCR-RFLP technique could be a potential method for identifying the food sources of arthropods. However, some points must be clarified regarding the applicability of the method, such as the extent of DNA degradation through intestinal digestion, the potential for multiple sources of blood meals and the need for greater knowledge regarding intraspecific variations in mtDNA.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131795PMC
http://dx.doi.org/10.1590/0074-0276130405DOI Listing
June 2014

Evaluation of tetravalent and conserved synthetic peptides vaccines derived from Dengue virus Envelope domain I and II.

Virus Res 2014 Aug 21;188:122-7. Epub 2014 Apr 21.

Laboratório de Vacinas, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Minas Gerais, Brazil. Electronic address:

Dengue is a major worldwide public health problem, especially in the tropical and subtropical regions of the world. Primary infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing a secondary infection with a different serotype progress to the severe form of the disease, called dengue hemorrhagic fever. In this study, the vaccine potential of three tetravalent and conserved synthetic peptides derived from DENV envelope domain I (named Pep01) and II (named Pep02 and Pep03) was evaluated. Human dengue IgM/IgG positive serum (n=16) showed reactivity against Pep01, Pep02 and Pep03 in different degrees. Mice immunization experiments showed that these peptides were able to induce a humoral response characterized by antibodies with low neutralizing activity. The spleen cells derived from mice immunized with the peptides showed a significant cytotoxic activity (only for Pep02 and Pep03), a high expression of IL-10 (P<0.01) and a reduced expression of TNF-α and IFN-gamma (P<0.001) compared to DENV-1 infected splenocytes. Thus these peptides, and specially the Pep03, can induce a humoral response characterized by antibodies with low neutralizing activities and probably a T cell response that could be beneficial to induce an effective immune response against all DENV serotypes and do not contributed to the immunopathogenesis. However, further studies in peptide sequence will be required to induce the production of neutralizing antibodies against all four DENV serotypes and also to improve immunogenicity of these peptides.
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http://dx.doi.org/10.1016/j.virusres.2014.04.009DOI Listing
August 2014

Evaluation of antimicrobial and cytotoxic activities of plant extracts from southern Minas Gerais cerrado.

Rev Inst Med Trop Sao Paulo 2014 Jan-Feb;56(1):13-20

Biomedical Science Institute, Microbiology and Immunology Department, Federal University of Alfenas, AlfenasMG, Brazil, Biomedical Science Institute, Microbiology and Immunology Department, Federal University of Alfenas, Alfenas, MG, Brazil.

The antimicrobial activity of plant hidroethanolic extracts on bacteria Gram positive, Gram negative, yeasts, Mycobacterium tuberculosis H37 and Mycobacterium bovis was evaluated by using the technique of Agar diffusion and microdilution in broth. Among the extracts evaluated by Agar diffusion, the extract of Bidens pilosa leaf presented the most expressive average of haloes of growth inhibition to the microorganisms, followed by the extract of B. pilosa flower, of Eugenia pyriformis' leaf and seed, of Plinia cauliflora leaf which statistically presented the same average of haloes inhibitory formation on bacteria Gram positive, Gram negative and yeasts. The extracts of Heliconia rostrata did not present activity. Mycobacterium tuberculosis H37 and Mycobacterium bovis (BCG) appeared resistant to all the extracts. The susceptibility profile of Candida albicans and Saccharomyces cerevisiae fungi were compared to one another and to the Gram positive Bacillus subtilis, Enterococcus faecalis and the Gram negative Salmonella typhimurium bacteria (p > 0.05). The evaluation of cytotoxicity was carried out on C6-36 larvae cells of the Aedes albopictus mosquito. The extracts of stem and flower of Heliconia rostrata, leaf and stem of Plinia cauliflora, seed of Anonna crassiflora and stem, flower and root of B. pilosa did not present toxicity in the analyzed concentrations. The highest rates of selectivity appeared in the extracts of stem of A. crassiflora and flower of B. pilosa to Staphylococcus aureus, presenting potential for future studies about a new drug development.
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http://dx.doi.org/10.1590/S0036-46652014000100002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085825PMC
April 2014

Bovine serum albumin nanoparticle vaccine reduces lung pathology induced by live Pseudomonas aeruginosa infection in mice.

Vaccine 2013 Oct 7;31(44):5062-6. Epub 2013 Sep 7.

Vaccine Laboratory, Institute of Biomedical Science, Federal University of Alfenas, Minas Gerais, Brazil.

Pseudomonas aeruginosa is an important opportunistic human pathogen that causes severe infections in immunocompromised patients and also in cystic fibrosis patients. The aim of this work was to study if a bovine serum albumin nanoparticles with entrapped antigens extracted from P. aeruginosa would be able to protect mice from nasal infection by this pathogen. Mice were immunized via the subcutaneous route using P. aeruginosa antigens, empty nanoparticles or nanoparticles with entrapped P. aeruginosa antigens on days 0, 7 and 14. The total IgG antibody production and specific IgG1 and IgG2a titer were measured by ELISA. Immunized mice were challenged with live P. aeruginosa and their lungs were collected for histopathology studies. Our data showed that NPPa-vaccinated mice presented a high anti-Pseudomonas IgG1 and a low IgG2a antibody titles and decreased inflammatory signs, with significant reduction in intensity and concentration of inflammatory cells, lower hemorrhagic, edema and hyperemia signs in the lungs of challenge mice with live P. aeruginosa if compared to the other groups. Therefore, this formulation is able to induce a functional response in an animal model of infection and thereby is a promising platform for P. aeruginosa vaccines.
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http://dx.doi.org/10.1016/j.vaccine.2013.08.078DOI Listing
October 2013

PCR detection of multiple human herpesvirus DNA in saliva from HIV-infected individuals in Teresina, State of Piauí, Brazil.

Rev Soc Bras Med Trop 2010 Nov-Dec;43(6):620-3

Parasitology and Microbiology Department, Federal University of Piauí, Teresina, PI, Brazil.

Introduction: Human herpesviruses are frequently associated with orofacial diseases in humans (HSV-1, EBV, CMV and HHV-8), some can also cause systemic disease (CMV and HHV-8). The transmission of these viruses occurs by contact with infected secretions, especially saliva. Human immunodeficiency virus infection is associated with an increased risk of HHVs and related diseases.

Methods: This work aimed to detect HSV-1, EBV, CMV and HHV-8 DNA in saliva of HIV-infected patients from Teresina, northeast Brazil, by PCR and compare these findings with age and sex matched HIV-seronegative individuals.

Results: No difference in prevalence was verified between HHV detection in the saliva of HIV-seropositive individuals and controls. The individual frequencies of these viruses in these two populations were different. HIV seropositivity correlated positively with the presence of CMV (OR: 18.2, p= 0.00032) and EBV (OR: 3.44, p= 0.0081). No association between CD4 counts and the prevalence of HHVs in the saliva was observed; however, a strong association was determined between seropositivity and the presence of multiple HHV DNAs in saliva (OR: 4.83, p = 0.0028).

Conclusions: These findings suggest the asymptomatic salivary shedding of HHVs is a common event between HIV-seropositive and seronegative individuals from Teresina, Piauí, Brazil, and, especially for HIV-seropositive patients, saliva is a risk factor for the acquisition/transmission of multiple HHVs.
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http://dx.doi.org/10.1590/s0037-86822010000600003DOI Listing
September 2011

Interferons and scleroderma-a new clue to understanding the pathogenesis of scleroderma?

Immunol Lett 2008 Jun 5;118(2):110-5. Epub 2008 May 5.

Laboratório de Microbiologia, Departamento de Parasitologia e Microbiologia, Centro de Ciências da Saúde, Universidade Federal do Piauí, Brazil.

Scleroderma or systemic sclerosis (SSc) is a complex disease characterized by vasculopathy and deregulated immune and fibroblast activation. The resulting excessive production of collagens and other extracellular matrix proteins by fibroblasts as well as the inflammatory response leads to the development of scleroderma. Recently, some emerging data have been showing a possible link between the type I and II interferons (IFNs) and SSc pathogenesis. IFNs are well-known immunomodulators and inhibitors of collagen production. However, IFN therapy also has been implicated in the development or exacerbation of several autoimmune diseases, including SSc. Some studies also showed an increase mRNA and protein levels of IFNs and several interferon stimulated genes in cells and tissues from SSc patients. In this review we discuss about a possible role for IFNs in SSc development and pathogenesis.
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http://dx.doi.org/10.1016/j.imlet.2008.03.016DOI Listing
June 2008

Increased expression of 2'5'oligoadenylate synthetase and double-stranded RNA dependent protein kinase messenger RNAs on affected skin of systemic sclerosis patients.

Arch Dermatol Res 2007 Aug 1;299(5-6):259-62. Epub 2007 Jun 1.

Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Scleroderma or systemic sclerosis (SSc) is an autoimmune disorder of unknown aetiology characterized by excessive collagen synthesis and subsequent deposition on the skin and various internal organs. Interferons (IFNs) are well-known immunomodulators and inhibitors of collagen production. However, IFN therapy has been implicated in the development or exacerbation of several autoimmune diseases, including SSc. We analyzed the expression of several interferon-stimulated genes (ISGs) in affected skin of SSc patients (skin tissue and cultured skin fibroblasts). A set of ISGs (PKR, 2'5'OAS, MxA, and 6-16) was analyzed by real-time PCR using RNA extracted from cultured skin fibroblasts and skin tissue of normal individuals and SSc patients. Both normal and SSc affected skin cultured fibroblasts were sensitive to the IFN treatment and presented similar levels of all ISGs tested. However, PKR and 2'5'OAS mRNA expression levels were significantly higher in the affected skin tissue of SSc patients when compared to normal controls. These data suggest that the IFN system plays a role in the pathogenesis of SSc.
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http://dx.doi.org/10.1007/s00403-007-0737-xDOI Listing
August 2007