RESUMEN
The presence of genetic mutations in HIV poses a significant challenge, potentially leading to antiretroviral resistance and hampering therapeutic development. The Brazilian population has presented variations in the HIV envelope V3 loop gene, especially the GWGR motif. This motif has been linked to reduced transmission potential and slower CD4+ T cell decline. This study aimed to assess clinical outcomes in patients with HIV-1 infected with strains containing the GWGR motif compared with those without it during long-term cART. A cohort of 295 patients with HIV was examined for the GWGR motif presence in the V3 loop. A total of 58 samples showed the GWGR signature, while 237 had other signatures. Multifactorial analyses showed no significant differences in demographic characteristics, CD4+ cell count, AIDS progression, or mortality between GWGR carriers and others. However, the mean interval between the first positive HIV test and the initial AIDS-defining event was more than two times longer for women carrying the GWGR signature (p = 0.0231). We emphasize the positive impact of cART on HIV/AIDS treatment, including viral suppression, CD4+ cell preservation, and immune function maintenance. Although no significant differences were found during cART, residual outcomes reflecting adherence challenges were observed between diagnosis and the first AIDS-defining event. The previously described outcomes, highlighting statistically significant differences between individuals carrying the GPGR motif compared with those with the Brazilian GWGR motif, may be directly linked to the natural progression of infection before advancements in cART. Presently, these physicochemical aspects may no longer hold the same relevance.
Asunto(s)
Infecciones por VIH , VIH-1 , Humanos , Femenino , VIH-1/genética , VIH-1/efectos de los fármacos , Masculino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Adulto , Recuento de Linfocito CD4 , Fármacos Anti-VIH/uso terapéutico , Persona de Mediana Edad , Resultado del Tratamiento , Secuencias de Aminoácidos , Carga Viral , Proteína gp120 de Envoltorio del VIH/genética , Estudios de Cohortes , Brasil , Terapia Antirretroviral Altamente Activa , Progresión de la Enfermedad , MutaciónRESUMEN
Despite care and the availability of effective antiretroviral treatment, some human immunodeficiency virus (HIV)-infected individuals suffer from neurocognitive disorders associated with HIV (HAND) that significantly affect their quality of life. The different types of HAND can be divided into asymptomatic neurocognitive impairment, mild neurocognitive disorder, and the most severe form known as HIV-associated dementia. Little is known about the mechanisms of HAND, but it is thought to be related to infection of astrocytes, microglial cells, and macrophages in the human brain. The formation of a viral reservoir that lies dormant as a provirus in resting CD4+ T lymphocytes and in refuge tissues such as the brain contributes significantly to HIV eradication. In recent years, a new set of tools have emerged: the gene editing based on the clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 system, which can alter genome segments by insertion, deletion, and replacement and has great therapeutic potential. This technology has been used in research to treat HIV and appears to offer hope for a possible cure for HIV infection and perhaps prevention of HAND. This approach has the potential to directly impact the quality of life of HIV-infected individuals, which is a very important topic to be known and discussed.
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Sistemas CRISPR-Cas , Edición Génica , Infecciones por VIH , Humanos , Edición Génica/métodos , Infecciones por VIH/terapia , Terapia Genética/métodos , Calidad de VidaRESUMEN
ABSTRACT The presence of genetic mutations in HIV poses a significant challenge, potentially leading to antiretroviral resistance and hampering therapeutic development. The Brazilian population has presented variations in the HIV envelope V3 loop gene, especially the GWGR motif. This motif has been linked to reduced transmission potential and slower CD4+ T cell decline. This study aimed to assess clinical outcomes in patients with HIV-1 infected with strains containing the GWGR motif compared with those without it during long-term cART. A cohort of 295 patients with HIV was examined for the GWGR motif presence in the V3 loop. A total of 58 samples showed the GWGR signature, while 237 had other signatures. Multifactorial analyses showed no significant differences in demographic characteristics, CD4+ cell count, AIDS progression, or mortality between GWGR carriers and others. However, the mean interval between the first positive HIV test and the initial AIDS-defining event was more than two times longer for women carrying the GWGR signature (p = 0.0231). We emphasize the positive impact of cART on HIV/AIDS treatment, including viral suppression, CD4+ cell preservation, and immune function maintenance. Although no significant differences were found during cART, residual outcomes reflecting adherence challenges were observed between diagnosis and the first AIDS-defining event. The previously described outcomes, highlighting statistically significant differences between individuals carrying the GPGR motif compared with those with the Brazilian GWGR motif, may be directly linked to the natural progression of infection before advancements in cART. Presently, these physicochemical aspects may no longer hold the same relevance.
RESUMEN
Environmental changes are among the main factors that contribute to the emergence or re-emergence of viruses of public health importance. Here, we show the impact of environmental modifications on cases of infections by the dengue, chikungunya and Zika viruses in humans in the state of Tocantins, Brazil, between the years 2010 and 2019. We conducted a descriptive and principal component analysis (PCA) to explore the main trends in environmental modifications and in the cases of human infections caused by these arboviruses in Tocantins. Our analysis demonstrated that the occurrence of El Niño, deforestation in the Cerrado and maximum temperatures had correlations with the cases of infections by the Zika virus between 2014 and 2016. El Niño, followed by La Niña, a gradual increase in precipitation and the maximum temperature observed between 2015 and 2017 were shown to have contributed to the infections by the chikungunya virus. La Niña and precipitation were associated with infections by the dengue virus between 2010 and 2012 and El Niño contributed to the 2019 outbreak observed within the state. By PCA, deforestation, temperatures and El Niño were the most important variables related to cases of dengue in humans. We conclude from this analysis that environmental changes (deforestation and climate change) presented a strong influence on the human infections caused by the dengue, chikungunya and Zika viruses in Tocantins from 2010 to 2019.
Asunto(s)
Fiebre Chikungunya , Virus del Dengue , Dengue , Infección por el Virus Zika , Virus Zika , Brasil/epidemiología , Fiebre Chikungunya/epidemiología , Dengue/epidemiología , Humanos , Infección por el Virus Zika/epidemiologíaRESUMEN
Circular single stranded DNA viruses (CRESS DNA) encoding a homologous replication-associated protein (REP) have been identified in most of eukaryotic groups. It is not clear yet the role in human diseases or details of the life cycle of these viruses. Recently, much interest has been raised in the evolutionary history of CRESS DNA owing to the increasing number of new sequences obtained by Next-Generation Sequencing (NGS) in distinct host species. In this study we describe two full-length CRESS DNA genomes obtained of two newly diagnosed HIV patients from São Paulo State, Brazil. The initial BLASTx search indicated that both sequences (named SP-FFB/2020 and SP-MJMS/2020) are highly similar (98%) to a previous CRESS DNA sequence detected in human fecal sample from Peru in 2016 and designated as pecovirus (Peruvian stool-associated circo-like virus). This study reported for the first time the Human feces pecovirus in the feces of two newly diagnosed HIV patients in Brazil. Our comparative analysis showed that although pecoviruses in South America share an identical genome structure they diverge and form distinct clades. Thus, we suggest the circulation of different species of pecoviruses in Latin America. Nevertheless, further studies must be done to examine the pathogenicity of this virus.
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Genoma Viral , Infecciones por VIH , Brasil/epidemiología , Virus ADN/genética , ADN de Cadena Simple , ADN Viral/genética , Heces , Genoma Viral/genética , Infecciones por VIH/genética , Humanos , FilogeniaRESUMEN
OBJECTIVE: To perform a molecular screening to detect infections by the mayaro virus and possible coinfections with Chikungunya during an outbreak in the state of Tocantins/Brazil in 2017. RESULTS: Of a total 102 samples analyzed in this study, 6 cases were identified with simultaneous infection between mayaro and chikungunya viruses (5.88%). In these 6 samples, the mean Cycle threshold (Ct) for CHIKV was 26.87 (SD ± 10.54) and for MAYV was 29.58 (SD ± 6.34). The mayaro sequences generated showed 95-100% identity to other Brazilian sequences of this virus and with other MAYV isolates obtained from human and arthropods in different regions of the world. The remaining samples were detected with CHIKV monoinfection (41 cases), DENV monoinfection (50 cases) and coinfection between CHIKV/DENV (5 cases). We did not detect MAYV monoinfections.
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Fiebre Chikungunya , Virus Chikungunya , Coinfección , Dengue , Brasil/epidemiología , Fiebre Chikungunya/diagnóstico , Fiebre Chikungunya/epidemiología , Virus Chikungunya/genética , Coinfección/epidemiología , Dengue/epidemiología , Brotes de Enfermedades , HumanosRESUMEN
To analyze the application of the metagenomics method in the identification of viral infectious agents that lead to diarrhea outbreaks. This study is a systematic review, which looked for publications on the following platforms: PubMed, Scientific Electronic Library Online (SciELO), LILACS and CAPES periodicals, conducted according to the PRISMA methodology, investigating in the literary composition studies related to metagenomics applied in the identification of viral infectious agents, which lead to diarrhea in humans. 1198 publications were identified. Of these, after analyzes and exclusions at different stages, 18 studies remained, which directly corresponded to the theme. Diarrhea was presented as a universal health concern. Despite the emergence of vaccines, cases of diarrhea remain persistent in poor populations. In this context, metagenomics emerges as a primary tool in detecting enteric viruses and identifying new viruses, revolutionizing health diagnoses, knowledge of viral diversity, and health surveillance, contributing to the correct etiology of infectious agents that would never be identified by conventional methods. The 18 articles studied point to advances in research in viral metagenomics of diarrheal samples, contributing to the discernment of diarrhea outbreaks, and properly associating with their etiological agents, they are presented in an innovative way for studies on the understanding of viral diversity.
Asunto(s)
Metagenómica , Virus , Diarrea/diagnóstico , Brotes de Enfermedades , Humanos , Metagenómica/métodos , Virus/genéticaRESUMEN
DNA methylation is one of the epigenetic modifications that configures gene transcription programs. This study describes the DNA methylation profile of HIV-infected individuals with distinct characteristics related to natural and artificial viremia control. Sheared DNA from circulating mononuclear cells was subjected to target enrichment bisulfite sequencing designed to cover CpG-rich genomic regions. Gene expression was assessed through RNA-seq. Hypermethylation in virologic responders was highly distributed closer to Transcription Start Sites (p-value = 0.03). Hyper and hypomethylation levels within TSS adjacencies varied according to disease progression status (Kruskal-Wallis, p < 0.001), and specific differentially methylated regions associated genes were identified for each group. The lower the promoter methylation, the higher the gene expression in subjects undergoing virologic failure (R = - 0.82, p = 0.00068). Among the inversely correlated genes, those supporting glycolysis and its related pathways were hypomethylated and up-regulated in virologic failures. Disease progression heterogeneity was associated with distinct DNA methylation patterns in terms of rates and distribution. Methylation was associated with the expression of genes sustaining intracellular glucose metabolism in subjects undergoing antiretroviral virologic failure. Our findings highlight that DNA methylation is associated with latency, disease progression, and fundamental cellular processes.
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Metilación de ADN , Epigénesis Genética , Regulación de la Expresión Génica , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Respuesta Virológica Sostenida , Latencia del Virus/genética , Adulto , Antirretrovirales/uso terapéutico , Estudios de Casos y Controles , Islas de CpG , Progresión de la Enfermedad , Femenino , Estudio de Asociación del Genoma Completo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Infecciones por VIH/patología , Humanos , Masculino , Persona de Mediana Edad , Regiones Promotoras GenéticasRESUMEN
BACKGROUND: The co-circulation of types of arbovirus in areas where they are endemic increased the risk of outbreaks and limited the diagnostic methods available. Here, we analyze the epidemiological profile of DENV, CHIKV and ZIKV at the serological and molecular level in patients with suspected infection with these arboviruses in the city of Juazeiro do Norte, Ceará, Brazil. METHODS: In 2016, the Central Public Health Laboratory (LACEN) of Juazeiro do Norte received 182 plasma samples from patients who visited health facilities with symptoms compatible with arbovirus infection. The LACEN performed serological tests for detection of IgM/IgG to DENV and CHIKV. They then sent these samples to the Retrovirology Laboratory of the Federal University of São Paulo and Faculty of Medical of the ABC where molecular analyses to confirm the infection by DENV, ZIKV and CHIKV were performed. The prevalence of IgM/IgG antibodies and of infections confirmed by RT-qPCR were presented with 95% confidence interval. RESULTS: In serologic analysis, 125 samples were positive for antibodies against CHIKV and all were positive for antibodies against DENV. A higher prevalence of IgG against CHIKV (63.20% with 95% CI: 45.76-70.56) than against DENV (95.05% with 95% CI: 78.09-98.12) was observed. When the samples were submitted to analysis by RT-qPCR, we observed the following prevalence: mono-infection by ZIKV of 19.23% (95% CI: 14.29-34.82) patients, mono-infection by CHIKV of 3.84% (95% CI: 2.01-5.44) and co-infection with ZIKV and CHIKV of 1.09% (95% CI: 0.89-4.56). CONCLUSION: The serologic and molecular tests performed in this study were effective in analyzing the epidemiological profile of DENV, CHIKV and ZIKV in patients with suspected infection by these arboviruses in the city of Juazeiro do Norte, Ceará/Brazil.
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Anticuerpos Antivirales/sangre , Fiebre Chikungunya/epidemiología , Virus Chikungunya/inmunología , Virus del Dengue/inmunología , Dengue/epidemiología , Infección por el Virus Zika/epidemiología , Virus Zika/inmunología , Adulto , Brasil/epidemiología , Fiebre Chikungunya/terapia , Ciudades/epidemiología , Estudios Transversales , Dengue/terapia , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Reacción en Cadena en Tiempo Real de la Polimerasa , Medición de Riesgo , Pruebas Serológicas , Infección por el Virus Zika/terapiaRESUMEN
During 2006-2011, 5035 fecal samples were tested by PCR for human adenovirus (HAdV) and sequenced. HAdV was detected in 198 cases (3.9%), with the highest rate in children ≤ 5 years. Enteric HAdVs were the most prevalent genotypes (78%; 146/187): HAdV-F41 (63.6%; 119/187), HAdV-F40 (12.3%; 23/187), HAdV-A12 (1.6%; 3/187) and HAdV-A31 (0.5%; 1/187). Non-enteric HAdVs were detected in 22% (41/187): HAdV-C1 (8.0%; 15/187), HAdV-C2 (6.9%; 13/187), HAdV-C5 (4.3%; 8/187), HAdV-D8 (1.3%; 2/187), HAdV-B21 (0.5%; 1/187), HAdV-B3 (0.5%; 1/187) and HAdV-C6 (0.5%; 1/187). This 6-year retrospective study points out a high diversity of HAdV types circulating in Brazil and highlights the need to carry out molecular epidemiological studies of HAdV among patients with acute diarrheal infection on a regular basis.
Asunto(s)
Infecciones por Adenovirus Humanos/epidemiología , Adenovirus Humanos/clasificación , Adenovirus Humanos/genética , Gastroenteritis/epidemiología , Adenovirus Humanos/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Niño , Preescolar , ADN Viral/genética , Heces/virología , Femenino , Gastroenteritis/virología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Estudios Retrospectivos , Adulto JovenRESUMEN
DNA methylation is one of the epigenetic modifications that configures gene transcription programs. This study describes the DNA methylation profile of HIV-infected individuals with distinct characteristics related to natural and artificial viremia control. Sheared DNA from circulating mononuclear cells was subjected to target enrichment bisulfite sequencing designed to cover CpG-rich genomic regions. Gene expression was assessed through RNA-seq. Hypermethylation in virologic responders was highly distributed closer to Transcription Start Sites (p-value = 0.03). Hyper and hypomethylation levels within TSS adjacencies varied according to disease progression status (Kruskal–Wallis, p < 0.001), and specific differentially methylated regions associated genes were identified for each group. The lower the promoter methylation, the higher the gene expression in subjects undergoing virologic failure (R = − 0.82, p = 0.00068). Among the inversely correlated genes, those supporting glycolysis and its related pathways were hypomethylated and up-regulated in virologic failures. Disease progression heterogeneity was associated with distinct DNA methylation patterns in terms of rates and distribution. Methylation was associated with the expression of genes sustaining intracellular glucose metabolism in subjects undergoing antiretroviral virologic failure. Our findings highlight that DNA methylation is associated with latency, disease progression, and fundamental cellular processes.
RESUMEN
BACKGROUND: The co-circulation of Chikungunya (CHIKV), Dengue (DENV) and Zika (ZIKV) viruses increased the risk of outbreaks and coinfections among them. Here, we report cases of coinfection in clinical samples from state of Tocantins, Brazil. METHODS: In 2017, the Central Public Health Laboratory (LACEN) received samples of patients who consulted health units with symptoms compatible with arboviral infections. A total of 102 samples were sent to the Retrovirology Laboratory at the Federal University of São Paulo, where they were tested by RT-qPCR to confirm DENV, ZIKV and CHIKV infections and to detect coinfected patients. RESULTS: We identified with CHIKV monoinfection (52), DENV serotypes 1 (28) and serotypes 2 (22). We did not detect ZIKV. Five patients were characterized with coinfection involving CHIKV and DENV serotype 2. CONCLUSIONS: The presence of co-circulating arboviruses increases the chance of coinfection and demonstrates the importance of differential diagnosis and vector control.
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Fiebre Chikungunya/epidemiología , Coinfección/epidemiología , Dengue/epidemiología , Infección por el Virus Zika/epidemiología , Adolescente , Adulto , Brasil/epidemiología , Fiebre Chikungunya/sangre , Fiebre Chikungunya/diagnóstico , Fiebre Chikungunya/genética , Virus Chikungunya/aislamiento & purificación , Niño , Coinfección/diagnóstico , Estudios Transversales , Dengue/sangre , Dengue/diagnóstico , Dengue/genética , Virus del Dengue/aislamiento & purificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Viral , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Serogrupo , Adulto Joven , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/sangreRESUMEN
ABSTRACT Background: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n = 25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. Results: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p = 0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p = 0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n = 4). Conclusion: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.
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Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Quinazolinas/farmacología , Azepinas/farmacología , Activación Viral/efectos de los fármacos , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Niacinamida/farmacología , Metiltransferasas/antagonistas & inhibidores , Piperazinas/farmacología , Leucocitos Mononucleares/virología , Linfocitos T CD4-Positivos , Regulación Viral de la Expresión Génica , Latencia del Virus , Carga Viral/efectos de los fármacos , Tropismo Viral/efectos de los fármacosRESUMEN
BACKGROUND: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n=17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n=25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. RESULTS: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p=0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p=0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n=4). CONCLUSION: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.
Asunto(s)
Azepinas/farmacología , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Metiltransferasas/antagonistas & inhibidores , Niacinamida/farmacología , Quinazolinas/farmacología , Activación Viral/efectos de los fármacos , Adulto , Linfocitos T CD4-Positivos , Femenino , Regulación Viral de la Expresión Génica , Humanos , Leucocitos Mononucleares/virología , Masculino , Persona de Mediana Edad , Piperazinas/farmacología , Carga Viral/efectos de los fármacos , Tropismo Viral/efectos de los fármacos , Latencia del Virus , Adulto JovenRESUMEN
In Brazil, flaviviruses have caused massive outbreaks. Surveillance programs designed to monitor virus activity in vectors provides a system for mapping disease distribution and for identifying specific vector species for targeted control. The present study aimed to describe the detection, whole genome characterization and phylogenetic analysis of Ilheus virus (ILHV) and Iguape virus (IGUV) strains obtained from historical mosquito's samples. Twelve isolates of pooled mosquito specimens (inoculated in neonate mouse brain) collected in the state of São Paulo, Brazil, in 1993, 1994 and 1997 were investigated. Viral RNA was extracted and analyzed by qRT-PCR using Flavivirus genus-specific primers. Positive samples were sequenced and underwent phylogenetic analyses. Flavivirus was detected in 50% of the specimens. Positive samples were successfully Sanger sequenced. Three Anopholes cruzii pools collected in 1994 were positive for IGUV. One Culex sp. pool, one Anopheles triannulatus pool, and one Coquillettidia juxtamansonia pool, collected in 1994, were positive for ILHV. Metagenomic sequencing successfully characterize one ILHV and four IGUV full genomes, and revealed a high degree of homology between the Brazilian ILHV and IGUV strains and isolates available in GenBank. Phylogenetic analysis of partial ILHV NS5 gene revealed three distinct lineages (clades), an indication of genetic heterogeneity in strains circulating in Brazil. Nucleotide insertions and a high-level of nucleotide diversity were observed in the NS1 protein and capsid region of IGUV strains, respectively. Detection of ILHV and IGUV in mosquitoes from Southeastern Brazil confirms the historical circulation of these viruses in this area. Furthermore, this first evidence of ILHV in Anopheles triannulatus suggests the potential importance of Anopheles mosquitoes in the IGUV transmission cycle. Genomic and phylogenetic analysis of these viruses provided insights into their diversity and evolution, which are important for the emergence patterns of flaviviruses and their evolutionary trends in Brazil, an endemic country for several arbovirus. in In-depth studies of ILHV and IGUV including vector competence and molecular studies are needed to shed light on their epidemiology and potential risk of future emergence.
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Culicidae/virología , Flavivirus/genética , Flavivirus/aislamiento & purificación , Genoma Viral , Animales , Secuencia de Bases , Brasil/epidemiología , Infecciones por Flaviviridae/epidemiología , Infecciones por Flaviviridae/virología , Ratones , Mosquitos Vectores/virología , Filogenia , ARN Viral/genéticaRESUMEN
Diarrhea remains one of the most common causes of deaths in children. Although many studies have investigated the prevalence of enteric pathogens around the globe some diarrheal episodes remain unexplained. It is possible that some yet-unidentified viral agents could be related to these cases of gastroenteritis. By using viral metagenomics techniques, we screened 251 fecal samples of children between 0.5 to 2.5-year-old with acute diarrhea not associated with common pathogens. These children live in rural areas and have different levels of contact with animals such as pigs, cows and bats. Here we report a complete genome of one mammalian orthoreovirus (MRV) type 3, denoted TO-151/BR, detected in a female child in the state of Tocantins (north of Brazil). Brazilian TO-151/BR strain was classified as MRV-3 based on S1 phylogeny and was closely related to porcine Asian strains. Phylogenetic analyses showed that other segments were more similar to MRV-3s of different geographic locations and hosts, including human and bats, highlighting genome reassortment and lack of host-specific barriers. This is the first report of MRV-3 in South America and a hypothesis of a silent long-term circulation of this virus in Brazil has been raised.
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Diarrea/virología , Gastroenteritis/virología , Intestinos/virología , Orthoreovirus Mamífero 3/clasificación , Animales , Brasil/epidemiología , Bovinos , Preescolar , Quirópteros , Microbioma Gastrointestinal , Genoma Viral , Geografía , Humanos , Lactante , Orthoreovirus Mamífero 3/aislamiento & purificación , Metagenómica , Filogenia , Población Rural , PorcinosRESUMEN
The resurgence of cases of Zika virus (ZIKV) infection, accompanied by epidemic of microcephaly in Brazil, has aroused worldwide interest in understanding the biological mechanisms of the virus that allow patient management and the viral dissemination control. Colostrum and human milk are possible sources of virus spread. Therefore, the objective of this study was to analyze the repercussions of ZIKV infection on rheological parameters and inflammatory cytokines of colostrum. The prospective cohort study included 40 puerperal donors of colostrum, divided into 2 groups: control (without ZIKV infection, n = 20) and a group infected with ZIKV during the gestational period (n = 20). Analyses were performed for the detection of ZIKV by polymerase chain reaction (PCR). In addition to obtaining the rheological parameters and quantification of IL-10 and IL-6 cytokines by flow cytometry, ZIKV and other flaviviruses were not detected in colostrum. However, maternal infection reflected increased viscosity, decreased levels of IL-10, and elevated levels of IL-6. The higher viscosity may represent a mechanical barrier that hinders the spread of the virus. The lower levels of anti-inflammatory mediators and higher inflammatory cytokines may possibly alter the viscosity, and it seems the higher viscosity represents a possible mechanism of adaptation of breastfeeding against a response to ZIKV.
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Calostro/inmunología , Interacciones Huésped-Patógeno/inmunología , Interleucina-10/inmunología , Interleucina-6/inmunología , Complicaciones Infecciosas del Embarazo/inmunología , Infección por el Virus Zika/inmunología , Virus Zika/patogenicidad , Adulto , Estudios de Casos y Controles , Calostro/química , Femenino , Expresión Génica , Humanos , Interleucina-10/genética , Interleucina-6/genética , Periodo Posparto/inmunología , Embarazo , Complicaciones Infecciosas del Embarazo/genética , Complicaciones Infecciosas del Embarazo/virología , Reología , Viscosidad , Virus Zika/inmunología , Infección por el Virus Zika/genética , Infección por el Virus Zika/virologíaRESUMEN
Human enteroviruses (EVs) are associated with a wide spectrum of human diseases. Here we report the complete genome sequences of one EV-C99 strain and one E29 strain obtained from children suffering from acute gastroenteritis, without symptoms of enteroviral syndromes. This is the first report of EV-C99 in South America, and the second E29 genome described worldwide. Continuous surveillance on EVs is vital to provide further understanding of the circulation of new or rare EV serotypes in the country. The present study also highlights the capacity of EVs to remain in silent circulation in populations.
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Enterovirus Humano B/genética , Enterovirus Humano C/genética , Infecciones por Enterovirus/virología , Anciano , Brasil , Preescolar , Enterovirus Humano B/aislamiento & purificación , Enterovirus Humano C/aislamiento & purificación , Heces/virología , Humanos , Masculino , Filogenia , ARN Viral/genéticaRESUMEN
We characterized the 24 nearly full-length genomes of human parechoviruses (PeV) from children in the north of Brazil. The initial phylogenetic analysis indicated that 17 strains belonged to genotype 1, 5 to genotype 4, and 1 to genotype 17. A more detailed analysis revealed a high frequency of recombinant strains (58%): A total of 14 of our PeV-As were chimeric, with four distinct recombination patterns identified. Five strains were composed of genotypes 1 and 5 (Rec1/5); five strains shared a complex mosaic pattern formed by genotypes 4, 5, and 17 (Rec4/17/5); two strains were composed of genotypes 1 and 17 (Rec1/17); and two strains were composed of genotype 1 and an undetermined strain (Rec1/und). Coalescent analysis based on the Vp1 gene, which is free of recombination, indicated that the recombinant strains most likely arose in this region approximately 30 years ago. They are present in high frequencies and are circulating in different small and isolated cities in the state of Tocantins. Further studies will be needed to establish whether the detected recombinant strains have been replacing parental strains or if they are co-circulating in distinct frequencies in Tocantins.
Asunto(s)
Genoma Viral , Parechovirus/genética , Infecciones por Picornaviridae/epidemiología , Virus Reordenados/genética , Recombinación Genética , Brasil/epidemiología , Preescolar , Heces/virología , Gastroenteritis/epidemiología , Gastroenteritis/virología , Variación Genética , Genotipo , Humanos , Lactante , Persona de Mediana Edad , Parechovirus/clasificación , Filogenia , Infecciones por Picornaviridae/virología , ARN Viral/genética , Virus Reordenados/clasificación , Población Rural , Análisis de Secuencia de ADN , Proteínas Virales/genéticaRESUMEN
Beginning in late 2016 Brazil faced the worst outbreak of Yellow Fever in recent decades, mainly located in southeastern rural regions of the country. In the present study we characterize the Yellow Fever Virus (YFV) associated with this outbreak in São Paulo State, Brazil. Blood or tissues collected from 430 dead monkeys and 1030 pools containing a total of 5,518 mosquitoes were tested for YFV by quantitative RT-PCR, immunohistochemistry (IHC) and indirect immunofluorescence. A total of 67 monkeys were YFV-positive and 3 pools yielded YFV following culture in a C6/36 cell line. Analysis of five nearly full length genomes of YFV from collected samples was consistent with evidence that the virus associated with the São Paulo outbreak originated in Minas Gerais. The phylogenetic analysis also showed that strains involved in the 2016-2017 outbreak in distinct Brazilian states (i.e., Minas Gerais, Rio de Janeiro, Espirito Santo) intermingled in maximum-likelihood and Bayesian trees. Conversely, the strains detected in São Paulo formed a monophyletic cluster, suggesting that they were local-adapted. The finding of YFV by RT-PCR in five Callithrix monkeys who were all YFV-negative by histopathology or immunohistochemistry suggests that this YFV lineage circulating in Sao Paulo is associated with different outcomes in Callithrix when compared to other monkeys.