Binding Evolution of the Dengue Virus Envelope Against DC-SIGN: A Combined Approach of Phylogenetics and Molecular Dynamics Analyses Over 30 Years of Dengue Virus in Brazil.

The Red Queen Hypothesis (RQH), derived from Lewis Carroll's "Through the Looking-Glass", postulates that organisms must continually adapt in response to each other to maintain relative fitness. Within the context of host-pathogen interactions, the RQH implies an evolutionary arms race, wherein viruses evolve to exploit hosts and hosts evolve to resist viral invasion. This study delves into the dynamics of the RQH in the context of virus-cell interactions, specifically focusing on virus receptors and cell receptors. We observed multiple virus-host systems and noted patterns of co-evolution. As viruses evolved receptor-binding proteins to effectively engage with cell receptors, cells countered by altering their receptor genes. This ongoing mutual adaptation cycle has influenced the molecular intricacies of receptor-ligand interactions. Our data supports the RQH as a driving force behind the diversification and specialization of both viral and host cell receptors. Understanding this co-evolutionary dance offers insights into the unpredictability of emerging viral diseases and potential therapeutic interventions. Future research is crucial to dissect the nuanced molecular changes and the broader ecological consequences of this ever-evolving battle. Here, we combine phylogenetic inferences, structural modeling, and molecular dynamics analyses to describe the epidemiological characteristics of major Brazilian DENV strains that circulated from 1990 to 2022 from a combined perspective, thus providing us with a more detailed picture on the dynamics of such interactions over time.

Low CCL2 and CXCL8 Production and High Prevalence of Allergies in Children with Microcephaly Due to Congenital Zika Syndrome.

Congenital Zika Syndrome (CZS) is associated with an increased risk of microcephaly in affected children. This study investigated the peripheral dysregulation of immune mediators in children with microcephaly due to CZS. Gene expression quantified by qPCR in whole blood samples showed an increase in IFNγ and IL-13 transcripts in children affected with microcephaly compared to the control group. The microcephaly group exhibited significantly decreased CCL2 and CXCL8 levels in serum, quantified by CBA assay. An allergic profile questionnaire revealed a high prevalence of allergies in the microcephaly group. In accordance, elevated serum IgE level measured by the Proquantum Immunoassay was observed in children affected with microcephaly compared to the control group. Altogether, these findings show a persistent systemic inflammation in children with microcephaly due to CZS and suggest a possible impairment in leukocyte migration caused by low production of CCL2 and CXCL8, in addition to high levels of IgE associated with high prevalence of allergies. The dysregulation of inflammatory genes and chemokines underscores the importance of understanding the immunological characteristics of CZS. Further investigation into the long-term consequences of systemic inflammation in these children is crucial for developing appropriate therapeutic strategies and tailored vaccination protocols.

Innate immune response in patients with acute Chikungunya disease.

Chikungunya disease (CHIKD) is an arbovirose that presents with high morbidity, mainly due to arthralgia. Inflammatory mediators including IL-6, IL-1ß, GM-CSF and others have been implicated in the pathogenesis of CHIKD, whilst type I interferons can be associated with better outcomes. The role of pattern recognition receptors has been studied incompletely. Here, we evaluated the expression of RNA-specific PRRs, their adaptor molecules and downstream cytokines in acute CHIKD patients. Twenty-eight patients were recruited during the 3rd-5th day after the symptoms onset for clinical examination, peripheral blood collection and qRT-PCR analysis of PBMC to compare to the healthy control group (n = 20). We observed common symptoms of acute CHIKD, with fever, arthralgia, headache and myalgia being the most frequent. Compared with uninfected controls, acute CHIKV infection upregulates the expression of the receptors TLR3, RIG-I and MDA5, and also the adaptor molecule TRIF. Regarding cytokine expression, we found an upregulation of IL-6, IL-12, IFN-α, IFN-ß and IFN-γ, which are related directly to the inflammatory or antiviral response. The TLR3-TRIF axis correlated with high expression of IL-6 and IFN-α. Interestingly, greater expression of MDA5, IL-12 and IFN-α was related to lower viral loads in CHIKD acute patients. Together, these findings help to complete the picture of innate immune activation during acute CHIKD, while confirming the induction of strong antiviral responses. Drawing the next steps in the understanding of the immunopathology and virus clearance mechanisms of CHIKD should be of utter importance in the aid of the development of effective treatment to reduce the severity of this debilitating disease.

Biology and Natural History of Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus is a clinical condition characterized by insufficient insulin production due to progressive loss of pancreatic islet ß-cells mediated by an autoimmune response. This deregulation of the immune system is caused by the action of genetic, epigenetic, and environmental factors in varying combinations for each individual. Although the inflammation of the islets with immune cell infiltration, known as insulitis, is an important element in pathogenesis, other factors are necessary for disease initiation. Associations with variants of HLA and other genes related to immune system function, mainly haplotypes HLA-DR3-DQ2 and HLA-DR4-DQ8, are more evident. The influence of polymorphisms and epigenetic modifications, as well as the microbiome, is convincing proof of the existence of a complex interaction between genetic, immune, and environmental factors in the etiology and pathogenesis of this metabolic disorder. Loss of selftolerance to autoimmunity is a critical point in the development of the disease, and regulatory T cells play a key role in this process. Thus, any failure of these cells, either due to an insufficient number or altered expression of cytokines and transcription factors, may be the trigger for the onset of the disease. The protective action of regulatory T cells is controlled by gene expression that is modulated by epigenetic modifications, including the dysregulation of noncoding RNAs. This review takes an updated approach to the natural history of type 1 diabetes, focusing on the factors involved in the etiology and pathogenesis.

Downregulation of CD73 on CD4+ T cells from patients with chronic Chikungunya infection.

Chikungunya is an important mosquito-borne disease caused by the arthritogenic chikungunya virus, characterized by sporadic outbreaks all around the world. Although CD4+ T cells seem to have an important role in the pathogenesis of chikungunya, the mechanisms involved in this process are not yet fully elucidated. The ectoenzymes CD39 and CD73, also expressed by CD4 T lymphocytes, are involved in the hydrolysis of pro-inflammatory extracellular ATP and generation of immunosuppressive adenosine and seem to be modulated in some arthritogenic pathologies. However, their involvement in Chikungunya disease is unclear. Thus, using flow cytometry, we investigated peripheral CD4+ T cells from patients with acute and chronic chikungunya to assess the expression of ectonucleotidases CD39 and CD73 and coinhibitory receptors and production of cytokine and cytolytic granules. Patients in the acute phase displayed increased levels of PD-1, CTLA-4, IL-10, and IFN-γ compared to healthy individuals and patients in the chronic phase. Moreover, during chronic Chikungunya, analyses of Mean Fluorescent Intensity (MFI) demonstrated a reduced density of LAP, Perforin and Granzyme B compared to the healthy control. Finally, reduced levels of the ectoenzymes CD39 and CD73 expression was found during the chronic phase suggesting a possible modulation of extracellular ATP and adenosine by CD4+ T cells that may be involved in the persistence of arthritogenic symptoms.

Regulatory T cells in acute and chronic human Chikungunya infection.

Chikungunya virus (CHIKV) infection generates strong immune responses that are associated with the disease pathophysiology. Regulatory T cells (Treg-cluster of differentiation (CD)-4+CD25highforkhead box P3 (FOXP3+)) are essential for the induction and maintenance of peripheral tolerance. Thus, they play key roles in determining the patient prognosis by preventing excessive immune responses via different suppression immune mechanisms. However, the regulatory mechanisms involved in human CHIKV infection are still poorly understood. Here, we characterize for the first time the Treg cell molecule-associated-mechanism during acute and chronic human Chikungunya disease. Here, we assessed the Treg cell population and molecule-associated mechanism in the peripheral blood samples of acute and chronic patients with Chikungunya. Our results indicate that CHIKV infection is associated with reduced frequency of Tregs, along with the impaired expression and production of Treg functional markers, including CD39, CD73, perforin, granzyme, programmed death 1 (PD-1), cytotoxic T lymphocyte antigen (CTLA)-4, and transforming growth factor (TGF)-ß. This observation suggests that Treg cells possess the poor regulatory capacity in both acute and chronic phases of the disease. Taken together, these data provide significant evidence that the imbalanced response of Treg cells plays an essential role in establishing the pathogenesis of Chikungunya.

Phenotypical characterization of regulatory T cells in acute Zika infection.

Zika virus (ZIKV), alongside Dengue virus (DENV), Chikungunya virus (CHIKV), and Yellow Fever Virus (YFV) are prevalent arboviruses in the Americas. Each of these infections is associated with the development of associated disease immunopathology. Immunopathological processes are an outcome of counter-balancing impacts between effector and regulatory immune mechanisms. In this context, regulatory T cells (Tregs) are key in modulating the immune response and, therefore, in tissue damage control. However, to date, Treg phenotypes and mechanisms during acute infection of the ZIKV in humans have not been fully investigated. The main aim of this work was to characterize Tregs and their immunological profile related to cytokine production and molecules that are capable of controlling the exacerbated inflammatory profile in acute Zika infected patients. Using whole blood analyses of infected patients, an ex vivo phenotypical characterization of Tregs, circulating during acute Zika virus infection, was conducted by flow cytometry. We found that though there are no differences in absolute Treg frequency between infected and healthy control groups. However, pro-inflammatory cytokine up-regulation such as IFN-γ and LAP was observed in the acute disease. Furthermore, acute ZIKV patients expressed increased levels of CD39/CD73, perforin/granzyme B, PD-1, and CTLA-4, all markers involved in mechanisms used by Tregs to attempt to control strong inflammatory responses. Thus, the data indicates a potential contribution of Tregs during the inflammatory ZIKV infection response.

The role of HPV-induced epigenetic changes in cervical carcinogenesis (Review).

Cervical cancer is associated with infection by certain types of human papillomaviruses (HPVs), and this affects women worldwide. Despite the improvements in prevention and cure of HPV-induced cervical cancer, it remains the second most common type of cancer in women in the least developed regions of the world. Epigenetic modifications are stable long-term changes that occur in the DNA, and are part of a natural evolutionary process of necessary adaptations to the environment. They do not result in changes in the DNA sequence, but do affect gene expression and genomic stability. Epigenetic changes are important in several biological processes. The effects of the environment on gene expression can contribute to the development of numerous diseases. Epigenetic modifications may serve a critical role in cancer cells, by silencing tumor suppressor genes, activating oncogenes, and exacerbating defects in DNA repair mechanisms. Although cervical cancer is directly related to a persistent high-risk HPV infection, several epigenetic changes have been identified in both the viral DNA and the genome of the infected cells: DNA methylation, histone modification and gene silencing by non-coding RNAs, which initiate and sustain epigenetic changes. In the present review, recent advances in the role of epigenetic changes in cervical cancer are summarized.

Evidence of Zika virus circulation in asymptomatic pregnant women in Northeast, Brazil.

BACKGROUND: Zika virus (ZIKV) is a flavivirus associated with microcephaly and other fetal anormalities. However, evidence of asymptomatic ZIKV infection in pregnant women is still scarce. This study investigated the prevalence of Zika infection in asymptomatic pregnant women attending two public maternities in Maranhão state, Northeast Brazil. METHODS: A total of 196 women were recruited at the time of delivery by convenience sampling from two maternity clinics in São Luís, Maranhão, Brazil, between April 2017 and June 2018. Venous blood, umbilical cord blood and placental fragments from maternal and fetal sides were collected from each subject. ZIKV infection was determined by reverse transcription polymerase chain reaction (RT-qPCR) for ZIKV and by serology (IgM and IgG). Nonspecific laboratory profiles (TORCH screen) were obtained from medical records. RESULTS: The participants were mostly from São Luís and were of 19-35 years of age. They had 10-15 years of schooling and they were of mixed race, married, and Catholic. ZIKV was identified in three umbilical cord samples and in nine placental fragments. Mothers with positive ZIKV RT-qPCR were in the age group older than 19 years. Of the 196 women tested by ZIKV rapid test, 6 and 117 women were positive for anti-ZIKV IgM and anti-ZIKV IgG antibodies, respectively. Placental Immunohistochemistry study detected ZIKV in all samples positive by RT-PCR. The newborns did not show any morphological and/or psychomotor abnormalities at birth. CONCLUSIONS: Asymptomatic ZIKV infection is frequent, but it was not associated to morphological and/or psychomotor abnormalities in the newborns up to 6 months post-birth. Although pathological abnormalities were not observed at birth, we cannot rule out the long term impact of apparent asymptomatic congenital ZIKV infection.

Ecological relationships of Haemagogus spegazzinii (Diptera: Culicidae) in a semiarid area of Brazil.

INTRODUCTION: Haemagogus are mosquitoes with diurnal habits that live preferentially in forest areas. In Brazil, they are considered the primary vectors of wild yellow fever. METHODS: The ecological relationships between Haemagogus spegazzinii, the environment, and some of its activities in the semiarid region of Rio Grande do Norte were analyzed by collecting eggs with ovitraps, actively searching in tree holes, capturing adults in Shannon traps, and conducting an investigation for viral infections. RESULTS: A total of 2420 eggs, 271 immature specimens (larvae and pupae), and 206 adults were collected. Egg collection depended on rainfall and relative humidity, with oviposition occurring between January and May. Larvae were found in five plant species, including Tabebuia aurea (craibeira), with 160 larvae collected. We observed shared breeding sites between Hg. spegazzinii and the following species: Aedes albopictus, Aedes terrens, Culex spp., and Toxorhynchites theobaldi. Adults exhibited greater activity between 5 pm and 6 pm, when 191 (92.7%) specimens were captured, while only 1 (0.5%) was collected between 7 pm and 8 pm. The relationship between Hg. spegazzinii and rainfall was significant, with positive correlations with accumulated rainfall 5, 10, 15, 20, and 30 days before mosquito collection. We found that the species was infected with the DENV-2 virus. CONCLUSIONS: This work contributes new information on the bioecology of Hg. spegazzinii, with data on the main reproduction periods, oviposition, breeding sites, activity times, and the relationship between the species and meteorological variables in the Caatinga of northeastern Brazil.

Biology and pathogenesis of human osteosarcoma.

Osteosarcoma (OS) is a bone tumor of mesenchymal origin, most frequently occurring during the rapid growth phase of long bones, and usually located in the epiphyseal growth plates of the femur or the tibia. Its most common feature is genome disorganization, aneuploidy with chromosomal alterations, deregulation of tumor suppressor genes and of the cell cycle, and an absence of DNA repair. This suggests the involvement of surveillance failures, DNA repair or apoptosis control during osteogenesis, allowing the survival of cells which have undergone alterations during differentiation. Epigenetic events, including DNA methylation, histone modifications, nucleosome remodeling and expression of non-coding RNAs have been identified as possible risk factors for the tumor. It has been reported that p53 target genes or those genes that have their activity modulated by p53, in addition to other tumor suppressor genes, are silenced in OS-derived cell lines by hypermethylation of their promoters. In osteogenesis, osteoblasts are formed from pluripotent mesenchymal cells, with potential for self-renewal, proliferation and differentiation into various cell types. This involves complex signaling pathways and multiple factors. Any disturbance in this process can cause deregulation of the differentiation and proliferation of these cells, leading to the malignant phenotype. Therefore, the origin of OS seems to be multifactorial, involving the deregulation of differentiation of mesenchymal cells and tumor suppressor genes, activation of oncogenes, epigenetic events and the production of cytokines.

Ecological relationships of Haemagogus spegazzinii (Diptera: Culicidae) in a semiarid area of Brazil

Abstract INTRODUCTION: Haemagogus are mosquitoes with diurnal habits that live preferentially in forest areas. In Brazil, they are considered the primary vectors of wild yellow fever. METHODS: The ecological relationships between Haemagogus spegazzinii, the environment, and some of its activities in the semiarid region of Rio Grande do Norte were analyzed by collecting eggs with ovitraps, actively searching in tree holes, capturing adults in Shannon traps, and conducting an investigation for viral infections. RESULTS: A total of 2420 eggs, 271 immature specimens (larvae and pupae), and 206 adults were collected. Egg collection depended on rainfall and relative humidity, with oviposition occurring between January and May. Larvae were found in five plant species, including Tabebuia aurea (craibeira), with 160 larvae collected. We observed shared breeding sites between Hg. spegazzinii and the following species: Aedes albopictus, Aedes terrens, Culex spp., and Toxorhynchites theobaldi. Adults exhibited greater activity between 5 pm and 6 pm, when 191 (92.7%) specimens were captured, while only 1 (0.5%) was collected between 7 pm and 8 pm. The relationship between Hg. spegazzinii and rainfall was significant, with positive correlations with accumulated rainfall 5, 10, 15, 20, and 30 days before mosquito collection. We found that the species was infected with the DENV-2 virus. CONCLUSIONS: This work contributes new information on the bioecology of Hg. spegazzinii, with data on the main reproduction periods, oviposition, breeding sites, activity times, and the relationship between the species and meteorological variables in the Caatinga of northeastern Brazil.

Tityus serrulatus Scorpion Venom Induces Apoptosis in Cervical Cancer Cell Lines.

Cervical cancer (CC) is classified as the fourth most common type of cancer in women worldwide and remains a serious public health problem in many underdeveloped countries. Human papillomavirus (HPV), mainly types 16 and 18, has been established as a precursory etiologic agent for this type of cancer. Several therapeutic attempts have been studied and applied, aiming at its control. However, not only do classical treatments such as chemotherapies and radiotherapies target tumor cells, but also they cause damage to several healthy cells. For these reasons, the search for new biologically active chemotherapeutic components is of great importance. In this study, we investigated the effect of Tityus serrulatus scorpion venom (TsV) on CC lines. There are very few studies exploring venom of scorpions, and, to our knowledge, no study has been conducted using the venom of the scorpion TsV for treatment of cervical cancer lines. After challenge with TsV, the MTT assay demonstrated cytotoxic effect on HeLa line. Similarly, the cell death process in HeLa analyzed by flow cytometry suggests death via caspase, since the pan-caspase inhibitor z-VAD-fmk significantly reduced the apoptotic response to the treatment. These results suggest that venom of TsV can be a potential source for the isolation of effective antiproliferative and apoptotic molecules in the treatment of CC.

Entomo-virological surveillance strategy for dengue, Zika and chikungunya arboviruses in field-caught Aedes mosquitoes in an endemic urban area of the Northeast of Brazil.

Aedes spp. are considered the main vectors of dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses in the world. Arbovirus detection in Aedes mosquitoes can alert authorities to possible outbreaks, reducing the impact of these diseases. The purpose of this study was to perform an operational strategy for virological surveillance of DENV, ZIKV and CHIKV in adult Aedes aegypti and Aedes albopictus mosquitoes captured at different key-sites in an endemic urban area of the Northeast Region of Brazil, with the prospect of discussing its role as part of an alert system for outbreaks in critical areas. Residential and non-residential premises located in areas of recent of transmission of these arboviruses were selected for adult mosquito collection in the rainy season (July) of 2018. A total of 1068 adult mosquitoes were collected: 946 Culex quinquefasciatus (88.6%), 118 Ae. aegypti (11.0%), two Ae. albopictus (0.2%) and two Aedes taeniorhynchus (0.2%). Among the premises surveyed, recycling points (N = 48, 40.7%), municipal schools (N = 36, 30.5%) and junkyards (N = 31, 26.2%) were the places with the highest frequency of adult Ae. aegypti. Health units (including primary health care facilities and one hospital) (N = 23; 19.5%) together with residential premises (N = 11; 9.3%) presented the lowest frequencies. Total RNAs of the samples were extracted from Aedes mosquitoes and a nested reverse transcription (RT) polymerase chain reaction (PCR) assay for detecting and typing DENV, ZIKV and CHIKV was performed. From the 37 Aedes spp. pools analyzed (35 Ae. aegypti, one Ae. albopictus and one Ae. taeniorhynchus), seven were positive for DENV-3, including three pools containing Ae. aegypti females, one containing an Ae. aegypti engorged female and three comprised of Ae. aegypti males. The positive pools were composed of mosquitoes collected in public schools, health units, junkyards, recycling points and residential premises. Our findings reinforce the importance of continuous virological surveillance in Aedes mosquitoes, as a useful tool for detecting arboviruses circulation in vulnerable areas, even in low infestation seasons.

Innate immune response in patients with acute Zika virus infection.

Innate immunity receptors (Toll-like receptors/TLRs and RIG-like receptors/RLRs) are important for the initial recognition of Zika virus (ZIKV), modulation of protective immune response, and IFN-α and IFN-ß production. Immunological mechanisms involved in protection or pathology during ZIKV infection have not yet been determined. In this study, we evaluated the mRNA expression of innate immune receptors (TLR3, TLR7, TLR8, TLR9, melanoma differentiation-associated protein 5/MDA-5, and retinoic acid inducible gene/RIG-1), its adapter molecules (Myeloid Differentiation Primary Response Gene 88/Myd88, Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-ß/TRIF), and cytokines (IL-6, IL-12, TNF-α, IFN-α, IFN-ß, and IFN-γ) in the acute phase of patients infected by ZIKV using real-time PCR in peripheral blood. Patients with acute ZIKV infection had high expression of TLR3, IFN-α, IFN-ß, and IFN-γ when compared to healthy controls. In addition, there was a positive correlation between TLR3 expression compared to IFN-α and IFN-ß. Moreover, viral load is positively correlated with TLR8, RIG-1, MDA-5, IFN-α, and IFN-ß. On the other hand, patients infected by ZIKV showed reduced expression of RIG-1, TLR8, Myd88, and TNF-α molecules, which are also involved in antiviral immunity. Similar expressions of TLR7, TLR9, MDA-5, TRIF, IL-6, and IL-12 were observed between the group of patients infected with ZIKV and control subjects. Our results indicate that acute infection (up to 5 days after the onset of symptoms) by ZIKV in patients induces the high mRNA expression of TLR3 correlated to high expression of IFN-γ, IFN-α, and IFN-ß, even though the high viral load is correlated to high expression of TLR8, RIG-1, MDA-5, IFN-α, and IFN-ß in ZIKV patients.

Tityus serrulatus scorpion venom induces apoptosis in cervical cancer cell lines

Cervical cancer (CC) is classified as the fourth most common type of cancer in women worldwide and remains a serious public health problem in many underdeveloped countries. Human papillomavirus (HPV), mainly types 16 and 18, has been established as a precursory etiologic agent for this type of cancer. Several therapeutic attempts have been studied and applied, aiming at its control. However, not only do classical treatments such as chemotherapies and radiotherapies target tumor cells, but also they cause damage to several healthy cells. For these reasons, the search for new biologically active chemotherapeutic components is of great importance. In this study, we investigated the effect of Tityus serrulatus scorpion venom (TsV) on CC lines. There are very few studies exploring venom of scorpions, and, to our knowledge, no study has been conducted using the venom of the scorpion TsV for treatment of cervical cancer lines. After challenge with TsV, the MTT assay demonstrated cytotoxic effect on HeLa line. Similarly, the cell death process in HeLa analyzed by flow cytometry suggests death via caspase, since the pan-caspase inhibitor z-VAD-fmk significantly reduced the apoptotic response to the treatment. These results suggest that venom of TsV can be a potential source for the isolation of effective antiproliferative and apoptotic molecules in the treatment of CC.

Tityus serrulatus scorpion venom induces apoptosis in cervical cancer cell lines

Cervical cancer (CC) is classified as the fourth most common type of cancer in women worldwide and remains a serious public health problem in many underdeveloped countries. Human papillomavirus (HPV), mainly types 16 and 18, has been established as a precursory etiologic agent for this type of cancer. Several therapeutic attempts have been studied and applied, aiming at its control. However, not only do classical treatments such as chemotherapies and radiotherapies target tumor cells, but also they cause damage to several healthy cells. For these reasons, the search for new biologically active chemotherapeutic components is of great importance. In this study, we investigated the effect of Tityus serrulatus scorpion venom (TsV) on CC lines. There are very few studies exploring venom of scorpions, and, to our knowledge, no study has been conducted using the venom of the scorpion TsV for treatment of cervical cancer lines. After challenge with TsV, the MTT assay demonstrated cytotoxic effect on HeLa line. Similarly, the cell death process in HeLa analyzed by flow cytometry suggests death via caspase, since the pan-caspase inhibitor z-VAD-fmk significantly reduced the apoptotic response to the treatment. These results suggest that venom of TsV can be a potential source for the isolation of effective antiproliferative and apoptotic molecules in the treatment of CC.

Th17 response in patients with cervical cancer.

Persistent infection by high-risk human papillomavirus (HR-HPV) is the main risk factor for uterine cervical cancer (UCC). However, viral infection alone is not sufficient for the development and progression of premalignant cervical lesions for cancer. In previous years it has been suggested that the adaptive immune response triggered by the differentiation of naïve helper T cells in Th17 cells may serve an important role in disease development. It has been hypothesized that Th17 cells may be involved in the promotion of UCC, as high levels of interleukin 17 (IL17) expression have been detected in the mucosa of the uterine cervix of patients affected by the disease. However, the role of Th17 cells in the tumor development and progression remains unclear. It is believed that the immune response of the Th17 type during persistent infection of the genital tract with HR-HPV triggers chronic inflammation with a long duration with the production of IL17 and other pro-inflammatory cytokines, creating a favorable environment for tumor development. These cytokines are produced by immune system cells in addition to tumor cells and appear to function by modulating the host immune system, resulting in an immunosuppressive response as opposed to inducing an effective protective immune response, thus contributing to the growth and progression of the tumor. In the present review, the latest advances are presented about the function of Th17 cells and the cytokines produced by them in the development and progression of UCC.

Human CD8 T-cell activation in acute and chronic chikungunya infection.

There is a need for more detailed elucidation of T-cell immunity in chikungunya infection. CD8 T cells are one of main actors against viruses. Here, we analysed CD8+ T lymphocytes from patients in the acute and chronic phases of chikungunya disease (CHIKD). Our results demonstrate that CD8+ T cells expressed higher ex vivo granzyme B, perforin and CD107A expression in patients in the acute phase of CHIKD compared with healthy individuals and higher ex vivo expression of CD69, interleukin-17A, interleukin-10 and CD95 ligand, and co-expression of CD95/CD95 ligand. These results elucidate the importance of these lymphocytes, demonstrating immune mechanisms mediated in human chikungunya infection.

Identification of surveillance and control priority areas for dengue and other arboviruses transmitted by Aedes aegypti in Natal-RN, Brazil: experience report. / Identificação de áreas prioritárias para a vigilância e controle de dengue e outras arboviroses transmitidas pelo Aedes aegypti no município de Natal-RN: relato de experiência.

OBJECTIVE: to report the vigi@dengue experience, held in the municipality of Natal-RN, Brazil, from October/2015 to May/2016. METHODS: entomological indicators were obtained from the oviposition traps, epidemiological indicators from notifications on the online Information System for Notifiable Diseases (Sinan-dengue), active search for cases and viral RNA detection (RTq-PCR) in arthropods and human serum samples; risk levels have been created based on these indicators; categories of interventions for each risk level have been established. RESULTS: early identification of epidemics in three areas of the municipality, with guidance for field work for the most vulnerable areas; the municipality presented ovitrap positivity index (OPI) of 40% and eggs density index (EDI) of 51 eggs/ovitraps; identification of CHIKV, DENV-1 and DENV-3 in Natal-RN. CONCLUSION: the strategy identified the early emergence of epidemics in specific locations; it was helpful in the guidance of control measures for the areas of major risk.