RESUMEN
The condition commonly referred to as long coronavirus disease (COVID) is characterized by the continuation of symptoms, sometimes accompanied by new symptoms that persist after the resolution of acute coronavirus disease 2019 (COVID-19). This observational cross-sectional study investigated 332 patients with long COVID in the Brazilian Amazon region. The study aimed to elucidate the systemic interactions associated with long COVID by compiling the findings related to hematological, coagulation, immunological, metabolic, hepatic, renal, and muscular profiles. Participants with long COVID were identified using rigorous criteria and underwent thorough laboratory examinations. The obtained data were subsequently analyzed, allowing for comparisons, associations, and correlations between findings within distinct groups in the study. Significant associations were observed between hospitalization during the acute phase and persistent laboratory abnormalities, suggesting a potential link between acute severity and long-term effects. Notably, individuals with long COVID for over a year exhibited elevated levels of monocytes, prolonged prothrombin times, reduced prothrombin activity, high levels of lactate dehydrogenase, and an increased frequency of qualitative C-reactive protein detection. This study provides valuable insights into the laboratory risk profile of patients with long COVID, particularly in the unique context of the Amazon region, where patients exhibit persistent symptoms lasting up to 1261 days.
Asunto(s)
COVID-19 , Humanos , COVID-19/sangre , COVID-19/epidemiología , COVID-19/diagnóstico , Brasil/epidemiología , Estudios Transversales , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , SARS-CoV-2 , Hospitalización/estadística & datos numéricos , Proteína C-Reactiva/análisis , Anciano de 80 o más AñosRESUMEN
Yellow fever (YF) is an infectious disease considered a public health problem in tropical and subtropical areas. YF has many pathophysiological events that are correlated with the host immune response. In this study, the in situ Th22 cytokine profile was evaluated. Liver tissue samples were collected from 21 YFV-positive patients who died of the disease and five flavivirus-negative controls who died of other causes and whose hepatic parenchyma architecture was preserved. Immunohistochemical (IHC) analysis of tissues in the hepatic parenchyma of YF cases showed significantly higher expression of interleukin (IL)-22, IL-13, tumour necrosis factor-alpha, and FGF basic (FGF b) in YFV-positive cases than that in flavivirus-negative controls. These results indicate that the response of Th22 cytokines emerges as an alternative for a better understanding of adaptive immunity in the hepatic parenchyma, highlighting the role of cytokines in the repair and suppressive responses in the immunopathogenesis of YFV infection.
Asunto(s)
Enfermedades Transmisibles , Flavivirus , Hepatopatías , Fiebre Amarilla , Citocinas , Humanos , Fiebre Amarilla/patología , Virus de la Fiebre AmarillaRESUMEN
BACKGROUND: There are several groups of viruses including Insect Specific Viruses (ISV) such as the taxon Negevirus, a group of viruses phylogenetically related to plant viruses. Negeviruses replicate in mosquito cells, but not in vertebrate cells. METHODS: Pools of hematophagous arthropods were inoculated in Vero and C6/36 cells. The cells were observed to detect possible cytopathic effect. Then, indirect immunofluorescence, RT-PCR, and nucleotide sequencing were performed. RESULTS: Seven samples which presented negative results for flaviviruses, alphaviruses and bunyaviruses, but showed cytopathic effect in C6/36 cells were sequenced. We identified the occurrence of a variety of ISVs, most of them belonging to the taxon Negevirus: The Brejeira, Negev, Cordoba and Wallerfield viruses, including a new virus for science, tentatively named Feitosa virus. CONCLUSIONS: We detected negeviruses in the Amazon region, including two viruses that were isolated for the first time in Brazil: Cordoba virus and the Negev virus and, a new virus for science: the Feitosa virus.
Asunto(s)
Culicidae , Virus de Insectos , Virus ARN , Animales , Brasil , Línea Celular , Virus de Insectos/genética , Filogenia , Virus ARN/genéticaRESUMEN
A new virus, named Mutum virus, related to members of the family Tymoviridae, was isolated from mosquitoes (Mansonia spp.) in clone C6/36 cells, and its complete genome was sequenced. Its genome is 6494 nt in size with an organization resembling that of tymovirids. The isolated virus is phylogenetically related to two viruses isolated from Culex spp. mosquitoes: Ek Balam virus, reported in Mexico, and Culex-originated Tymoviridae-like virus, isolated in China. The results of this study suggest that this virus is a new member of the family Tymoviridae.
Asunto(s)
Culex , Culicidae , Malvaceae , Tymoviridae , Animales , Brasil , Genoma Viral , Filogenia , Tymoviridae/genéticaRESUMEN
We evaluated the duration of neutralizing antibodies and the status of 17DD vaccine-specific T- and B-cell memory following primary and revaccination regimens for yellow fever (YF) in Brazil. We observed progressive decline of plaque-reduction neutralization test (PRNT) seropositivity and of the levels of effector memory CD4+ and CD8+ T cells, as well as interferon-γ+CD8+ T cells, 10 years after primary vaccination. Revaccination restored PRNT seropositivity as well as the levels of effector memory CD4+, CD8+, and interferon-γ+CD8+ T cells. Moreover, secondary or multiple vaccinations guarantee long-term persistence of PRNT positivity and cell-mediated memory 10 years after booster vaccination. These findings support the relevance of booster doses to heighten the 17DD-YF-specific immune response to guarantee the long-term persistence of memory components. Secondary or multiple vaccinations improved the correlates of protection triggered by 17DD-YF primary vaccination, indicating that booster regimens are needed to achieve efficient immunity in areas with high risk for virus transmission.
Asunto(s)
Inmunidad , Inmunización Secundaria , Vacuna contra la Fiebre Amarilla/inmunología , Fiebre Amarilla/inmunología , Fiebre Amarilla/prevención & control , Virus de la Fiebre Amarilla/inmunología , Adolescente , Adulto , Anciano , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Brasil/epidemiología , Virus del Dengue/inmunología , Femenino , Humanos , Inmunidad Celular , Inmunoglobulina G/inmunología , Memoria Inmunológica , Masculino , Persona de Mediana Edad , Pruebas de Neutralización , Vigilancia en Salud Pública , Vacuna contra la Fiebre Amarilla/administración & dosificación , Adulto JovenRESUMEN
Human cytomegalovirus (HCMV) is a widespread opportunistic herpesvirus that causes severe diseases in immunocompromised individuals. It has a high prevalence worldwide that is linked with socioeconomic factors. Similar to other herpesviruses, HCMV has the ability to establish lifelong persistence and latent infection following primary exposure. HCMV infects a broad range of cell types. This broad tropism suggests that it may use multiple receptors for host cell entry. The identification of receptors used by HCMV is essential for understanding viral pathogenesis, because these receptors mediate the early events necessary for infection. Many cell surface components have been identified as virus receptors, such as epidermal growth factor receptor (EGFR), which is characterized by tyrosine kinase activity and plays a crucial role in the control of key cellular transduction pathways. EGFR is essential for HCMV binding, signaling, and host cell entry. This review focuses on HCMV infection via EGFR on different cell types and its implications for the cellular environment, viral persistence, and infection.
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Infecciones por Citomegalovirus/metabolismo , Infecciones por Citomegalovirus/virología , Citomegalovirus/fisiología , Receptores ErbB/metabolismo , Interacciones Huésped-Patógeno , Animales , Citomegalovirus/clasificación , Humanos , Ligandos , Unión Proteica , Transducción de SeñalRESUMEN
Zika virus is a mosquito-borne flavivirus, firstly identified in Uganda and responsible for sporadic human cases in Africa and Asia until recently, when large outbreak occurred in Pacific Ocean and the Americas. Since the main vectors during its spread outside of Africa have been Ae. albopictus and Ae. aegypti mosquitoes, which are widely distributed all over the world, there is urgent need for a coordinated response for prevention and spread of ZIKV epidemics.Despite clinical manifestation of Zika virus infection are usually mild and self limiting, there are reports suggesting, during the recent epidemic, an association of ZIKV infection with severe consequences, including fetal/newborn microcephaly, due to vertical in utero transmission, autoimmune-neurological presentations including cranial nerve dysfunction, and Guillain-Barré Syndrome in adults. The primary mode of transmission of Zika virus between humans is through the bite of an infected female mosquito of the Aedes genus, but also sexual and blood transfusion transmission may occur. Moreover, a case of non-sexual spread from one person to another has been described, indicating that we still have more to learn about Zika transmission.Biological basis for pathogenetic effects are under investigation. Laboratory diagnosis is challenging since, so far, there are no "gold standard" diagnostic tools, and the low and short viremia in the acute phase, and together with the high cross-reactivity among the members of flavivirus genus are the most challenging aspects to be overcome.
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Enfermedades Transmisibles Emergentes/virología , Salud Global/tendencias , Infección por el Virus Zika/epidemiología , Virus Zika/genética , Animales , Infecciones del Sistema Nervioso Central/patología , Infecciones del Sistema Nervioso Central/virología , Brotes de Enfermedades , Reservorios de Enfermedades , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Insectos Vectores , Microcefalia/virología , Filogenia , Enfermedades Virales de Transmisión Sexual , Infección por el Virus Zika/patología , Infección por el Virus Zika/transmisión , Infección por el Virus Zika/virologíaRESUMEN
BACKGROUND: Few studies have explored the glial response to a standard environment and how the response may be associated with age-related cognitive decline in learning and memory. Here we investigated aging and environmental influences on hippocampal-dependent tasks and on the morphology of an unbiased selected population of astrocytes from the molecular layer of dentate gyrus, which is the main target of perforant pathway. RESULTS: Six and twenty-month-old female, albino Swiss mice were housed, from weaning, in a standard or enriched environment, including running wheels for exercise and tested for object recognition and contextual memories. Young adult and aged subjects, independent of environment, were able to distinguish familiar from novel objects. All experimental groups, except aged mice from standard environment, distinguish stationary from displaced objects. Young adult but not aged mice, independent of environment, were able to distinguish older from recent objects. Only young mice from an enriched environment were able to distinguish novel from familiar contexts. Unbiased selected astrocytes from the molecular layer of the dentate gyrus were reconstructed in three-dimensions and classified using hierarchical cluster analysis of bimodal or multimodal morphological features. We found two morphological phenotypes of astrocytes and we designated type I the astrocytes that exhibited significantly higher values of morphological complexity as compared with type II. Complexity = [Sum of the terminal orders + Number of terminals] × [Total branch length/Number of primary branches]. On average, type I morphological complexity seems to be much more sensitive to age and environmental influences than that of type II. Indeed, aging and environmental impoverishment interact and reduce the morphological complexity of type I astrocytes at a point that they could not be distinguished anymore from type II. CONCLUSIONS: We suggest these two types of astrocytes may have different physiological roles and that the detrimental effects of aging on memory in mice from a standard environment may be associated with a reduction of astrocytes morphological diversity.
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Astrocitos/metabolismo , Astrocitos/patología , Factores de Edad , Animales , Cognición/fisiología , Giro Dentado/citología , Giro Dentado/metabolismo , Ambiente , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Hipocampo/citología , Hipocampo/fisiología , Memoria/fisiología , RatonesRESUMEN
The long-term laboratory aspects of the effects of coronavirus disease 2019 (COVID-19) on liver function are still not well understood. Therefore, this study aimed to evaluate the hepatic clinical laboratory profile of patients with up to 20 months of long-term COVID-19. A total of 243 patients of both sexes aged 18 years or older admitted during the acute phase of COVID-19 were included in this study. Liver function analysis was performed. Changes were identified in the mean levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and ferritin. A ferritin level of >300 U/L was observed in the group that presented more changes in liver function markers (ALT, AST, and GGT). Age ≥ 60 years, male sex, AST level > 25 U/L, and GGT level ≥ 50 or 32 U/L were associated with an ALT level > 29 U/L. A correlation was found between ALT and AST, LDH, GGT, and ferritin. Our findings suggest that ALT and AST levels may be elevated in patients with long-term COVID-19, especially in those hospitalised during the acute phase. In addition, an ALT level > 29 U/L was associated with changes in the levels of other markers of liver injury, such as LDH, GGT, and ferritin.
Asunto(s)
COVID-19 , Femenino , Humanos , Masculino , COVID-19/epidemiología , Estudios Transversales , Hígado/metabolismo , Pruebas de Función Hepática , gamma-Glutamiltransferasa , Ferritinas , Alanina Transaminasa/metabolismo , Aspartato Aminotransferasas/metabolismoRESUMEN
INTRODUTION AND OBJECTIVE: The present study sought to characterize the pattern of monocyte subpopulations in patients during the course of the infections caused by SARS-CoV-2 virus or who presented long COVID-19 syndrome compared to monocytes from patients with zika virus (Zika) or chikungunya virus (CHIKV). CASUISTRY: Study with 89 peripheral blood samples from patients, who underwent hemogram and serology (IgG and IgM) for detection of Zika (Control Group 1, n = 18) or CHIKV (Control Group 2, n = 9), and from patients who underwent hemogram and reverse transcription polymerase chain reaction for detection of SARS-CoV-2 at the acute phase of the disease (Group 3, n = 19); and of patients who presented long COVID-19 syndrome (Group 4, n = 43). The monocyte and subpopulations counts were performed by flow cytometry. RESULTS: No significant difference was observed in the total number of monocytes between the groups. The classical (CD14++CD16-) and intermediate (CD14+CD16+) monocytes counts were increased in patients with acute infection or with long COVID-19 syndrome. The monocytes subpopulations counts were lower in patients with infection Zika or CHIKV. CONCLUSION: Increase in the monocyte subpopulations in patients with acute infection or with long COVID-19 syndrome may be an important finding of differentiated from the infection Zika or CHIKV.
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COVID-19 , Virus Chikungunya , Infección por el Virus Zika , Virus Zika , Humanos , Monocitos , Síndrome Post Agudo de COVID-19 , SARS-CoV-2 , Infección por el Virus Zika/diagnóstico , Receptores de IgG , Receptores de LipopolisacáridosRESUMEN
BACKGROUND: Chewing imbalances are associated with neurodegeneration and are risk factors for senile dementia in humans and memory deficits in experimental animals. We investigated the impact of long-term reduced mastication on spatial memory in young, mature and aged female albino Swiss mice by stereological analysis of the laminar distribution of CA1 astrocytes. A soft diet (SD) was used to reduce mastication in the experimental group, whereas the control group was fed a hard diet (HD). Assays were performed in 3-, 6- and 18-month-old SD and HD mice. RESULTS: Eating a SD variably affected the number of astrocytes in the CA1 hippocampal field, and SD mice performed worse on water maze memory tests than HD mice. Three-month-old mice in both groups could remember/find a hidden platform in the water maze. However, 6-month-old SD mice, but not HD mice, exhibited significant spatial memory dysfunction. Both SD and HD 18-month-old mice showed spatial memory decline. Older SD mice had astrocyte hyperplasia in the strata pyramidale and oriens compared to 6-month-old mice. Aging induced astrocyte hypoplasia at 18 months in the lacunosum-moleculare layer of HD mice. CONCLUSIONS: Taken together, these results suggest that the impaired spatial learning and memory induced by masticatory deprivation and aging may be associated with altered astrocyte laminar distribution and number in the CA1 hippocampal field. The underlying molecular mechanisms are unknown and merit further investigation.
Asunto(s)
Envejecimiento/fisiología , Astrocitos/fisiología , Región CA1 Hipocampal/fisiología , Masticación/fisiología , Aprendizaje por Laberinto/fisiología , Trastornos de la Memoria/fisiopatología , Animales , Astrocitos/citología , Región CA1 Hipocampal/citología , RatonesRESUMEN
The COVID-19 pandemic initiated a race to determine the best measures to control the disease and to save as many people as possible. Efforts to implement social distancing, the use of masks, and massive vaccination programs turned out to be essential in reducing the devastating effects of the pandemic. Nevertheless, the high mutation rates of SARS-CoV-2 challenge the vaccination strategy and maintain the threat of new outbreaks due to the risk of infection surges and even lethal variations able to resist the effects of vaccines and upset the balance. Most of the new therapies tested against SARS-CoV-2 came from already available formulations developed to treat other diseases, so they were not specifically developed for SARS-CoV-2. In parallel, the knowledge produced regarding the molecular mechanisms involved in this disease was vast due to massive efforts worldwide. Taking advantage of such a vast molecular understanding of virus genomes and disease mechanisms, a targeted molecular therapy based on siRNA specifically developed to reach exclusive SARS-CoV-2 genomic sequences was tested in a non-transformed human cell model. Since coronavirus can escape from siRNA by producing siRNA inhibitors, a complex strategy to simultaneously strike both the viral infectious mechanism and the capability of evading siRNA therapy was developed. The combined administration of the chosen produced siRNA proved to be highly effective in successfully reducing viral load and keeping virus replication under control, even after many days of treatment, unlike the combinations of siRNAs lacking this anti-anti-siRNA capability. Additionally, the developed therapy did not harm the normal cells, which was demonstrated because, instead of testing the siRNA in nonhuman cells or in transformed human cells, a non-transformed human thyroid cell was specifically chosen for the experiment. The proposed siRNA combination could reduce the viral load and allow the cellular recovery, presenting a potential innovation for consideration as an additional strategy to counter or cope COVID-19.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Pandemias , Replicación Viral/genética , Genoma Viral , ARN Interferente Pequeño/genéticaRESUMEN
Yellow fever (YF) is a pansystemic disease caused by the yellow fever virus (YFV), the prototype species of the family Flaviviridae and genus Flavivirus, and has a highly complex host-pathogen relationship, in which endothelial dysfunction reflects viral disease tropism. In this study, the in situ endothelial response was evaluated. Liver tissue samples were collected from 21 YFV-positive patients who died due to the disease and five flavivirus-negative controls who died of other causes and whose hepatic parenchyma architecture was preserved. Immunohistochemical analysis of tissues in the hepatic parenchyma of YF cases showed significantly higher expression of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and very late antigen-4 in YFV-positive cases than in flavivirus-negative controls. These results indicate that endothelium activation aggravates the inflammatory response by inducing the expression of adhesion molecules that contribute to the rolling, recruitment, migration, and construction of the inflammatory process in the hepatic parenchyma in fatal YF cases.
RESUMEN
Yellow fever (YF), a non-contagious infectious disease, is endemic or enzootic to the tropical regions of the Americas and Africa. Periodic outbreaks or epidemics have a significant impact on public health. Programmed cell death, or apoptosis, is generally characterised by distinct morphological changes and energy-dependent biochemical pathways. In this study, we performed immunohistochemistry analysis to identify and quantify proteases and protein targets involved in the cascade that triggers apoptosis in YF virus (YFV)-infected human hepatocytes. Liver tissue samples were collected from 26 individuals, among whom 21 were diagnosed as YF-positive, and five were flavivirus-negative and died due to other causes. The histopathological alterations in YFV-positive cases were characterised by the presence of apoptotic bodies, steatosis, cellular swelling, and extensive necrosis and haemorrhage in the hepatic lobules. Additionally, we observed an abundance of inflammatory infiltrates in the portal tract. The expression of various apoptotic markers in the hepatic parenchyma, including CASPASE 3, CASPASE 8, BAX, FAS, FASL, GRANZYME B, and SURVIVIN, differed between YFV-positive cases and controls. Collectively, this study confirmed the complexity of YFV infection-induced apoptosis in situ. However, our data suggest that apoptosis in liver parenchyma lesions may significantly contribute to the pathogenesis of fatal YF in humans.
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Epidemias , Hepatitis A , Hepatitis , Fiebre Amarilla , Apoptosis , Hepatitis A/epidemiología , Humanos , Virus de la Fiebre AmarillaRESUMEN
BACKGROUND: The emergence and re-emergence of infectious diseases are a cause for worldwide concern. The introduction of Zika and Chikungunya diseases in the Americas has exposed unforeseen medical and logistical challenges for public health systems. Moreover, the lack of preventive measures and vaccination against known and emerging mosquito-transmitted pathogens, and the occurrence of unanticipated clinical complications, has had an enormous social and economic impact on the affected populations. In this study, we aimed to measure the seroprevalence of endemic and emerging viral pathogens in military personnel stationed in Manaus, Amazonas state. METHODS: We measured the seropositivity of antibodies against 19 endemic and emerging viruses in a healthy military personnel group using a hemagglutination inhibition assay (HIA). RESULTS: Overall, DENV positivity was 60.4%, and 30.9% of the individuals reacted against ZIKV. Also, 46.6%, 54.7%, 51.3% and 48.7% individuals reacted against West Nile virus (WNV), Saint Louis encephalitis virus (SLEV), Ilheus virus (ILHV) and Rocio virus (ROCV), respectively. Individuals with high DENV HIA titer reacted more frequently with ZIKV or WNV compared to those with low HIA titers. Observed cross-reactivity between Flaviviruses varied depending on the virus serogroup. Additionally, 0.6% and 0.3% individuals were seropositive for Oropouche virus (OROV) and Catu virus (CATUV) from the family Peribunyaviridae, respectively. All samples were negative for Eastern Equine Encephalitis virus (EEEV), Western Equine Encephalomyelitis virus (WEEV), Mayaro virus (MAYV), Mucambo virus (MUCV) and CHIKV from the family Togaviridae. CONCLUSIONS: A high proportion of individuals in our high-risk population (~ 60%) lacked antibodies against major endemic and emerging viruses, which makes them susceptible for further infections. Military personnel serving in the Amazon region could serve as sentinels to strengthen global infectious disease surveillance, particularly in remote areas.
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Anticuerpos Antivirales/sangre , Infecciones por Arbovirus/inmunología , Arbovirus/inmunología , Adulto , Factores de Edad , Infecciones por Arbovirus/epidemiología , Arbovirus/clasificación , Brasil , Virus del Dengue/inmunología , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Personal Militar/estadística & datos numéricos , Prevalencia , Estudios Seroepidemiológicos , Virus del Nilo Occidental/inmunología , Adulto Joven , Virus Zika/inmunología , Infección por el Virus Zika/sangre , Infección por el Virus Zika/inmunologíaRESUMEN
The Culicidae family is distributed worldwide and comprises about 3587 species subdivided into the subfamilies Anophelinae and Culicinae. This is the first description of complete mitochondrial DNA sequences from Aedes fluviatilis, Aedeomyia squamipennis, Coquillettidia nigricans, Psorophora albipes, and Psorophora ferox. The mitogenomes showed an average length of 15,046 pb and 78.02% AT content, comprising 37 functional subunits (13 protein coding genes, 22 tRNAs, and two rRNAs). The most common start codons were ATT/ATG, and TAA was the stop codon for all PCGs. The tRNAs had the typical leaf clover structure, except tRNASer1. Phylogeny was inferred by analyzing the 13 PCGs concatenated nucleotide sequences of 48 mitogenomes. Maximum likelihood and Bayesian inference analysis placed Ps. albipes and Ps. ferox in the Janthinosoma group, like the accepted classification of Psorophora genus. Ae. fluviatilis was placed in the Aedini tribe, but was revealed to be more related to the Haemagogus genus, a result that may have been hampered by the poor sampling of Aedes sequences. Cq. nigricans clustered with Cq. chrysonotum, both related to Mansonia. Ae. squamipennis was placed as the most external lineage of the Culicinae subfamily. The yielded topology supports the concept of monophyly of all groups and ratifies the current taxonomic classification.
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Culicidae/genética , Genoma Mitocondrial/genética , Aedes/genética , Animales , Composición de Base/genética , Brasil , Codón/genética , Culicidae/metabolismo , ADN Mitocondrial/genética , Conformación de Ácido Nucleico , Sistemas de Lectura Abierta/genética , Filogenia , ARN Ribosómico/genética , ARN de Transferencia/genéticaRESUMEN
During the Zika virus (ZIKV) outbreak in Brazil (2015-2016), the clinical manifestations associated with its infection were complex and included miscarriage and congenital malformations, not previously described. In this study, we evaluated the prenatal conditions of pregnant female squirrel monkeys (Saimiri collinsi) infected during different gestational thirds (GTs) and assessed all clinical aspects, diagnostic imaging, viremia and the immune response. In our study, 75% of the infected animals in the 1st GT group had significant clinical manifestations, such as miscarriage and prolonged viremia associated with a late immune response. Consequently, their neonates showed fetal neuropathology, such as cerebral hemorrhage, lissencephaly or malformations of the brain grooves, ventriculomegaly, and craniofacial malformations. Thus, our study demonstrated the relevance of pregnant squirrel monkeys as a model for the study of ZIKV infection in neonates due to the broad clinical manifestations presented, including the typical congenital Zika syndrome manifestations described in humans.
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Enfermedades Fetales , Microcefalia , Enfermedades de los Monos , Saimiri/virología , Infección por el Virus Zika , Virus Zika/metabolismo , Animales , Brasil/epidemiología , Femenino , Enfermedades Fetales/epidemiología , Enfermedades Fetales/metabolismo , Enfermedades Fetales/veterinaria , Enfermedades Fetales/virología , Microcefalia/embriología , Microcefalia/metabolismo , Microcefalia/virología , Enfermedades de los Monos/epidemiología , Enfermedades de los Monos/metabolismo , Enfermedades de los Monos/virología , Embarazo , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/metabolismo , Infección por el Virus Zika/veterinariaRESUMEN
The absence of an adequate animal model for studies has limited the understanding of congenital Zika syndrome (CZS) in humans during the outbreak in America. In this study, we used squirrel monkeys (Saimiri collinsi), a neotropical primate (which mimics the stages of human pregnancy), as a model of Zika virus (ZIKV) infection. Seven pregnant female squirrel monkeys were experimentally infected at three different gestational stages, and we were able reproduce a broad range of clinical manifestations of ZIKV lesions observed in newborn humans. Histopathological and immunohistochemical analyses of early-infected newborns (2/4) revealed damage to various areas of the brain and ZIKV antigens in the cytoplasm of neurons and glial cells, indicative of CZS. The changes caused by ZIKV infection were intrauterine developmental delay, ventriculomegaly, simplified brain gyri, vascular impairment and neuroprogenitor cell dysfunction. Our data show that the ZIKV infection outcome in squirrel monkeys is similar to that in humans, indicating that this model can be used to help answer questions about the effect of ZIKV infection on neuroembryonic development and the morphological changes induced by CZS.
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Encéfalo , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika , Virus Zika , Animales , Animales Recién Nacidos , Encéfalo/embriología , Encéfalo/patología , Encéfalo/virología , Femenino , Embarazo , Complicaciones Infecciosas del Embarazo/patología , Complicaciones Infecciosas del Embarazo/virología , Saimiri , Síndrome , Infección por el Virus Zika/embriología , Infección por el Virus Zika/patologíaRESUMEN
Macrophages are a functionally heterogeneous group of cells with specialized functions depending not only on their subgroup but also on the function of the organ or tissue in which the cells are located. The concept of macrophage phenotypic heterogeneity has been investigated since the 1980s, and more recent studies have identified a diverse spectrum of phenotypic subpopulations. Several types of macrophages play a central role in the response to infectious agents and, along with other components of the immune system, determine the clinical outcome of major infectious diseases. Here, we review the functions of various macrophage phenotypic subpopulations, the concept of macrophage polarization, and the influence of these cells on the evolution of infections. In addition, we emphasize their role in the immune response in vivo and in situ, as well as the molecular effectors and signaling mechanisms used by these cells. Furthermore, we highlight the mechanisms of immune evasion triggered by infectious agents to counter the actions of macrophages and their consequences. Our aim here is to provide an overview of the role of macrophages in the pathogenesis of critical transmissible diseases and discuss how elucidation of this relationship could enhance our understanding of the host-pathogen association in organ-specific immune responses.