RESUMO
During its global epidemic, Zika virus (ZIKV) attracted widespread attention due to its link with various severe neurological symptoms and potential harm to male fertility. However, the understanding of how ZIKV invades and persists in the male reproductive system is limited due to the lack of immunocompetent small animal models. In this study, immunocompetent murine models were generated by using anti-IFNAR antibody blocked C57BL/6 male mice and human STAT2 (hSTAT2) knock in (KI) male mice. After infection, viral RNA could persist in the testes even after the disappearance of viremia. We also found a population of ZIKV-susceptible S100A4+ monocytes/macrophages that were recruited into testes from peripheral blood and played a crucial role for ZIKV infection in the testis. By using single-cell RNA sequencing, we also proved that S100A4+ monocytes/macrophages had a great impact on the microenvironment of ZIKV-infected testes, thus promoting ZIKV-induced testicular lesions. In conclusion, this study proposed a novel mechanism of long-term ZIKV infection in the male reproductive system.
Assuntos
Infecção por Zika virus , Zika virus , Humanos , Masculino , Camundongos , Animais , Zika virus/genética , Testículo , Monócitos , Camundongos Endogâmicos C57BL , Macrófagos , Modelos Animais de Doenças , Proteína A4 de Ligação a Cálcio da Família S100RESUMO
Viral encephalitis continues to be a significant public health concern. In our previous study, we discovered a lower expression of antiviral factors, such as IFN-ß, STING and IFI16, in the brain tissues of patients with Rasmussen's encephalitis (RE), a rare chronic neurological disorder often occurred in children, characterized by unihemispheric brain atrophy. Furthermore, a higher cumulative viral score of human herpes viruses (HHVs) was also found to have a significant positive correlation with the unihemispheric atrophy in RE. Type I IFNs (IFN-I) signaling is essential for innate anti-infection response by binding to IFN-α/ß receptor (IFNAR). In this study, we infected WT mice and IFNAR-deficient A6 mice with herpes simplex virus 1 (HSV-1) via periocular injection to investigate the relationship between IFN-I signaling and HHVs-induced brain lesions. While all mice exhibited typical viral encephalitis lesions in their brains, HSV-induced epilepsy was only observed in A6 mice. The gene expression matrix, functional enrichment analysis and protein-protein interaction network revealed four gene models that were positively related with HSV-induced epilepsy. Additionally, ten key genes with the highest scores were identified. Taken together, these findings indicate that intact IFN-I signaling can effectively limit HHVs induced neural symptoms and brain lesions, thereby confirming the positive correlation between IFN-I signaling repression and brain atrophy in RE and other HHVs encephalitis.
Assuntos
Epilepsia , Herpes Simples , Herpesvirus Humano 1 , Interferon Tipo I , Transdução de Sinais , Animais , Feminino , Camundongos , Encéfalo/patologia , Encéfalo/virologia , Modelos Animais de Doenças , Encefalite por Herpes Simples/virologia , Encefalite por Herpes Simples/imunologia , Encefalite por Herpes Simples/patologia , Epilepsia/virologia , Epilepsia/patologia , Herpes Simples/virologia , Herpes Simples/patologia , Herpes Simples/imunologia , Herpesvirus Humano 1/patogenicidade , Herpesvirus Humano 1/imunologia , Interferon Tipo I/metabolismo , Interferon Tipo I/imunologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mapas de Interação de Proteínas , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/deficiênciaRESUMO
Single-cell RNA sequencing (scRNA-seq) has allowed for the profiling of host and virus transcripts and host-virus interactions at single-cell resolution. This review summarizes the existing scRNA-seq technologies together with their strengths and weaknesses. The applications of scRNA-seq in various virological studies are discussed in depth, which broaden the understanding of the immune atlas, host-virus interactions, and immune repertoire. scRNA-seq can be widely used for virology in the near future to better understand the pathogenic mechanisms and discover more effective therapeutic strategies.
Assuntos
Perfilação da Expressão Gênica , Interações entre Hospedeiro e Microrganismos , Análise de Sequência de RNA , Interações entre Hospedeiro e Microrganismos/genéticaRESUMO
IMPORTANCE: Zika virus (ZIKV) infection in pregnant women during the third trimester can cause neurodevelopmental delays and cryptorchidism in children without microcephaly. However, the consequences of congenital ZIKV infection on fertility in these children remain unclear. Here, using an immunocompetent mouse model, we reveal that congenital ZIKV infection can cause hormonal disorders of the hypothalamic-pituitary-gonadal axis, leading to reduced fertility and decreased sexual preference. Our study has for the first time linked the hypothalamus to the reproductive system and social behaviors after ZIKV infection. Although the extent to which these observations in mice translate to humans remains unclear, these findings did suggest that the reproductive health and hormone levels of ZIKV-exposed children should receive more attention to improve their living quality.
Assuntos
Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Animais , Criança , Feminino , Humanos , Masculino , Camundongos , Gravidez , Fertilidade , Hormônios , Eixo Hipotalâmico-Hipofisário-Gonadal , Microcefalia , Complicações Infecciosas na Gravidez/virologia , Zika virus/fisiologia , Infecção por Zika virus/patologiaRESUMO
Zika virus (ZIKV) is a potential threat to male reproductive health but the mechanisms underlying its influence on testes during ZIKV infection remain obscure. To address this question, we perform single-cell RNA sequencing using testes from ZIKV-infected mice. The results reveal the fragility of spermatogenic cells, especially spermatogonia, to ZIKV infection and show that the genes of the complement system are significantly upregulated mainly in infiltrated S100A4 + monocytes/macrophages. Complement activation and its contribution to testicular damage are validated by ELISA, RTâqPCR and IFA and further verify in ZIKV-infected northern pigtailed macaques by RNA genome sequencing and IFA, suggesting that this might be the common response to ZIKV infection in primates. On this basis, we test the complement inhibitor C1INH and S100A4 inhibitors sulindac and niclosamide for their effects on testis protection. C1INH alleviates the pathological change in the testis but deteriorates ZIKV infection in general. In contrast, niclosamide effectively reduces S100A4 + monocyte/macrophage infiltration, inhibits complement activation, alleviates testicular damage, and rescues the fertility of male mice from ZIKV infection. This discovery therefore encourages male reproductive health protection during the next ZIKV epidemic.
Assuntos
Infecção por Zika virus , Zika virus , Masculino , Camundongos , Animais , Zika virus/genética , Niclosamida , Ativação do Complemento , Análise de Sequência de RNARESUMO
Zika virus (ZIKV) poses a serious threat to global public health due to its close relationship with neurological and male reproductive damage. However, deficiency of human testicular samples hinders the in-depth research on ZIKV-induced male reproductive system injury. Organoids are relatively simple in vitro models, which could mimic the pathological changes of corresponding organs. In this study, we constructed a 3D testicular organoid model using primary testicular cells from adult BALB/c mice. Similar to the testis, this organoid system has a blood-testis barrier (BTB)-like structure and could synthesize testosterone. ZIKV tropism of testicular cells and ZIKV-induced pathological changes in testicular organoid was also similar to that in mammalian testis. Therefore, our results provide a simple and reproducible in vitro testicular model for the investigations of ZIKV-induced testicular injury.
Assuntos
Infecção por Zika virus , Zika virus , Masculino , Humanos , Camundongos , Animais , Testículo/patologia , Organoides/patologia , MamíferosRESUMO
As a member of vector-borne viruses, Zika virus (ZIKV) can cause microcephaly and various neurological symptoms in newborns. Previously, we found that ZIKV could infect hypothalamus, causing a decrease in growth hormone (GH) secretion, growth delay and deficits in learning and memory in suckling mice. Early administration of GH can improve the cognitive function of the mice. Therefore, in this study we further investigated the mechanism underlying the protective role of GH in ZIKV infection in suckling mice. Our results showed that GH could effectively reduce brain damage caused by ZIKV infection via reducing cell apoptosis and inflammatory response rather than inhibiting viral replication. Our results provide important evidences not only for understanding the mechanism underlying ZIKV-associated neurological symptoms but also for the treatment of ZIKV infection.
Assuntos
Microcefalia , Infecção por Zika virus , Zika virus , Animais , Encéfalo , Hormônio do Crescimento/farmacologia , Camundongos , Replicação Viral , Zika virus/fisiologia , Infecção por Zika virus/tratamento farmacológicoRESUMO
BACKGROUND: The etiology of Rasmussen's encephalitis (RE), a rare chronic neurological disorder characterized by CD8+ T cell infiltration and unihemispheric brain atrophy, is still unknown. Various human herpes viruses (HHVs) have been detected in RE brain, but their contribution to RE pathogenesis is unclear. METHODS: HHVs infection and relevant immune response were compared among brain tissues from RE, temporal lobe epilepsy (TLE) and traumatic brain injury (TBI) patients. Viral antigen or genome, CD8+ T cells, microglia and innate immunity molecules were analyzed by immunohistochemical staining, DNA dot blot assay or immunofluorescence double staining. Cytokines were measured by multiplex flow cytometry. Cell apoptosis was visualized by TUNEL staining. Viral infection, immune response and the severity of unihemispheric atrophy were subjected to correlation analysis. RESULTS: Antigens of various HHVs were prevalent in RE and TLE brains, and the cumulative viral score of HHVs positively correlated with the unihemispheric atrophy in RE patients. CD8+ T cells infiltration were observed in both RE and TLE brains and showed co-localization with HHV antigens, but their activation, as revealed by Granzyme B (GZMB) release and apoptosis, was found only in RE. In comparison to TLE, RE brain tissues contained higher level of inflammatory cytokines, but the interferon-ß level, which was negatively correlated with cumulative viral score, was relatively lower. In line with this, the DNA sensor STING and IFI16, rather than other innate immunity signaling molecules, were insufficiently activated in RE. CONCLUSIONS: Compared with TBI, both RE and TLE had prevalently HHV infection and immune response in brain tissues. However, in comparison to TLE, RE showed insufficient activation of antiviral innate immunity but overactivation of cytotoxic T cells. Our results show the relatively lower level of antiviral innate immunity and overactivation of cytotoxic T cells in RE cases upon HHV infection, the overactivated T cells might be a compensate to the innate immunity but the causative evidence is lack in our study and need more investigation in the future.
Assuntos
Encefalite , Epilepsia do Lobo Temporal , Vírus , Encéfalo/metabolismo , Encefalite/patologia , Epilepsia do Lobo Temporal/patologia , Humanos , Interferon beta , Vírus/metabolismoRESUMO
Chikungunya fever is an acute infectious disease caused by the chikungunya virus (CHIKV) that is characterized by fever, rash, and joint pain. CHIKV has infected millions of people in Africa, Asia, America, and Europe since it re-emerged in the Indian Ocean region in 2004. Here, we report an outbreak of Chikungunya fever that occurred in Ruili of Yunnan Province, a city located on the border between China and Myanmar, in September 2019. The outbreak lasted for three months from September to December. Overall, 112 cases were confirmed by a real-time reverse-transcription polymerase chain reaction in the Ruili People's Hospital, and they showed apparent temporal, spatial, and population aggregation. Among them, 91 were local cases distributed in 19 communities of Ruili City, and 21 were imported cases. The number of female patients was higher than that of male patients, and most patients were between 20 and 60 years old. The main clinical manifestations included joint pain (91.96%), fever (86.61%), fatigue (58.04%), chills (57.14%), rash (48.21%), headache (39.29%), and so forth. Biochemical indexes revealed increased C-reactive protein (63.39%), lymphopenia (57.17%), increased hemoglobin (33.04%), neutrophilia (28.57%), and thrombocytopenia (16.07%). Phylogenetic analysis of the complete sequences indicated that the CHIKV strains in this outbreak belonged to the Indian Ocean clade of the East/Central/South African genotype. We speculated that this chikungunya outbreak might be caused by CHIKV-infected persons returning from Myanmar, and provided a reference for the formulation of effective treatment and prevention measures.
Assuntos
Febre de Chikungunya/epidemiologia , Febre de Chikungunya/fisiopatologia , Vírus Chikungunya/isolamento & purificação , Filogenia , Adulto , Artralgia/etiologia , Vírus Chikungunya/genética , China/epidemiologia , Cidades/epidemiologia , Surtos de Doenças , Feminino , Febre/etiologia , Genoma Viral/genética , Humanos , Leucopenia/etiologia , Masculino , Pessoa de Meia-Idade , Mianmar , Reação em Cadeia da Polimerase em Tempo Real , Trombocitopenia/etiologia , Adulto JovemRESUMO
BACKGROUND: Few studies have evaluated the long-term relationship between diet quality and cardiometabolic risk factor clustering among children. The moderating effect of socio-economic status (SES) is of interest. OBJECTIVE: To investigate the association between diet quality with cardiometabolic risk among Chinese children and to explore the moderating effect of SES. DESIGN: In this cohort study, 5 waves (1997-2009) of the China Health and Nutrition Survey were used. Diet quality was measured by a modified version of the Chinese Children Dietary Index (mCCDI) based on Dietary Guidelines for Chinese. PARTICIPANTS: Children between the ages of 7 and 17 (n = 2903) who completed at least 2 surveys were included. Those who missed measures or had hypertension or diabetes at baseline were excluded. MAIN OUTCOME MEASURES: The fasting blood samples were collected in 2009. Waist circumference (WC) and blood pressure (BP) were measured in each survey. STATISTICAL ANALYSIS PERFORMED: A continuous cardiometabolic risk score (MetScore) was derived by a confirmatory factor analysis of 5 components: WC, BP, glucose, triglycerides, and high-density lipoprotein cholesterol. Considering the latency period of the effect of behaviors, the mCCDI was lagged by the period between surveys. Linear regression was used to analyze the association of mCCDI with MetScore and its components. Mixed effect linear regression and lagged mCCDI were used for WC and BP models. RESULTS: Higher mCCDI was independently associated with a lower MetScore at follow-up (ß: -.11; 95% CI: -.18 to -.04). Higher lagged mCCDI over time was associated with a lower WC z score overall (ß: -.05; 95% CI: -.08 to -.01) and among children in the low SES group (ß: -.09; 95% CI: -.14 to -.04) but not those in the high SES group. When examining the 15 mCDDI components separately, scores for 5 components: more grains, vegetables, soybeans and its products; less sugar-sweetened beverages; and more diet variety were significantly associated with a lower MetScore. CONCLUSIONS: Among Chinese children, higher diet quality measured by mCCDI was independently associated with a lower MetScore at follow-up.
Assuntos
Fatores de Risco Cardiometabólico , Dieta Saudável/estatística & dados numéricos , Classe Social , Adolescente , Glicemia/análise , Pressão Sanguínea , Criança , China , Análise por Conglomerados , Análise Fatorial , Feminino , Humanos , Modelos Lineares , Lipoproteínas HDL/sangue , Masculino , Inquéritos Nutricionais , Medição de Risco , Triglicerídeos/sangue , Circunferência da CinturaRESUMO
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus, which causes the most commonly diagnosed viral encephalitis named Japanese encephalitis (JE) in the world with an unclear pathogenesis. Axl, a receptor tyrosine kinase from TAM family, plays crucial role in many inflammatory diseases. We have previously discovered that Axl deficiency resulted in more severe body weight loss in mice during JEV infection, which we speculate is due to the anti-inflammatory effect of Axl during JE. Currently, the role of Axl in regulating the neuroinflammation and brain damage during JE has not been investigated yet. In this study, by using Axl deficient and heterozygous control mice, we discovered that Axl deficient mice displayed accelerated JE progression and exacerbated brain damage characterized by increased neural cell death, extended infiltration of inflammatory cells, and enhanced production of pro-inflammatory cytokines, in comparison to control mice. Additionally, consistent with our previous report, Axl deficiency had no impact on the infection and target cell tropism of JEV in brain. Taken together, our results suggest that Axl plays an anti-inflammatory and neuroprotective role during the pathogenesis of JE.
Assuntos
Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Animais , Encéfalo/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , CamundongosRESUMO
Tyro3, Axl, and Mertk (TAM) receptors play multiple roles in a myriad of physiological and pathological processes, varying from promoting the phagocytic clearance of apoptotic cells, sustaining the immune and inflammatory homeostasis, maintaining the blood-brain barrier (BBB) integrity and central nervous system (CNS) homeostasis, to mediating cancer malignancy and chemoresistance. Growth arrest-specific protein 6 (Gas6) and protein S (Pros1) are the two ligands that activate TAM receptors. Recently, TAM receptors have been reported to mediate cell entry and infection of multitudinous enveloped viruses in a manner called apoptotic mimicry. Moreover, TAM receptors are revitalized during viral entry and infection, which sequesters innate immune and inflammatory responses, facilitating viral replication and immune evasion. However, accumulating evidence have now proposed that TAM receptors are not required for the infection of these viruses in vivo. In addition, TAM receptors protect mice against the CNS infection of neuroinvasive viruses and relieve the brain lesions during encephalitis. These protective effects are achieved through maintaining BBB integrity, attenuating proinflammatory cytokine production, and promoting neural cell survival. TAM receptors also regulate the programmed cell death modes of virus-infected cells, which have profound impacts on the pathogenesis and outcome of infection. Here, we systematically review the functionalities and underlying mechanisms of TAM receptors and propose the potential application of TAM agonists to prevent severe viral encephalitis.
Assuntos
Receptores Proteína Tirosina Quinases , Viroses , Animais , Camundongos , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais , c-Mer Tirosina Quinase/metabolismoRESUMO
Testicular invasion and persistence are features of Zika virus (ZIKV), but their mechanisms are still unknown. Here, we showed that S100A4+ macrophages, a myeloid macrophage subpopulation with susceptibility to ZIKV infection, facilitated ZIKV invasion and persistence in the seminiferous tubules. In ZIKV-infected mice, S100A4+ macrophages were specifically recruited into the interstitial space of testes and differentiated into interferon-γ-expressing M1 macrophages. With interferon-γ mediation, S100A4+ macrophages down-regulated Claudin-1 expression and induced its redistribution from the cytosol to nucleus, thus increasing the permeability of the blood-testis barrier which facilitated S100A4+ macrophages invasion into the seminiferous tubules. Intraluminal S100A4+ macrophages were segregated from CD8+ T cells and consequently helped ZIKV evade cellular immunity. As a result, ZIKV continued to replicate in intraluminal S100A4+ macrophages even when the spermatogenic cells disappeared. Deficiencies in S100A4 or interferon-γ signaling both reduced ZIKV infection in the seminiferous tubules. These results demonstrated crucial roles of S100A4+ macrophages in ZIKV infection in testes.
Assuntos
Macrófagos/metabolismo , Proteína A4 de Ligação a Cálcio da Família S100/imunologia , Infecção por Zika virus/imunologia , Animais , Claudina-1/genética , Claudina-1/metabolismo , Interferon gama/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Viral , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo , Túbulos Seminíferos/virologia , Testículo/imunologia , Testículo/virologia , Replicação Viral/imunologia , Replicação Viral/fisiologia , Zika virus/imunologia , Infecção por Zika virus/virologiaRESUMO
Japanese encephalitis virus (JEV) is a flavivirus that causes Japanese encephalitis (JE), which has an unclear pathogenesis. Despite vaccination, thousands of deaths attributed to JE are reported annually. In this study, we report that mice deficient for Axl, a receptor tyrosine kinase that plays multiple roles in flaviviral infection, displayed greater mortality upon JEV infection. The effect of Axl deficiency on JEV infection was mediated by markedly elevated serum interleukin-1α (IL-1α) levels, which devastated the blood-brain-barrier and promoted viral neuroinvasion within 24 h postinfection. Using an in situ infection model, we showed that dead macrophages were the primary source of observed increased serum IL-1α levels. Axl deficiency enhanced cell death and caused pyroptosis in 80% of JEV-infected macrophages by disrupting phosphatidylinositol 3-kinase (PI3K)-Akt signaling. Intriguingly, the primary effector released by pyroptotic macrophages in our model was IL-1α rather than IL-1ß. Finally, we assessed the effect of an IL-1α antagonist and demonstrated that it effectively prevented the incidence of JE. Our results indicate that Axl plays a protective role in JEV infection, identify IL-1α released by pyroptotic macrophages as a crucial factor promoting JEV neuroinvasion, and suggest that an IL-1α antagonist may be a candidate for JE therapy.IMPORTANCE Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes Japanese encephalitis (JE), the most commonly diagnosed viral encephalitis worldwide. The fatality rate of JE is 20%, and nearly half of the surviving patients develop neuropsychiatric sequelae. Axl is a receptor tyrosine kinase that plays multiple roles in flaviviral infections. Currently, the involvement of Axl in JEV infection remains enigmatic. In this study, we demonstrate that Axl impedes the pathogenesis of severe JE in mice by maintaining blood-brain-barrier (BBB) integrity and restricting viral neuroinvasion. Furthermore, serum IL-1α is a key mediator of this process and is primarily released by JEV-infected pyroptotic macrophages to elicit BBB breakdown, while an IL-1α antagonist can effectively reduce the incidence of severe JE. Our work uncovers the protective role of Axl in antagonizing severe JE and shows that the use of an IL-1α antagonist may be a promising tactic to prevent severe JE.
Assuntos
Vírus da Encefalite Japonesa (Espécie)/fisiologia , Encefalite Japonesa/virologia , Interleucina-1alfa/metabolismo , Macrófagos/metabolismo , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/virologia , Modelos Animais de Doenças , Encefalite Viral/virologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Fosfatidilinositol 3-Quinases/metabolismo , Piroptose , Receptor Tirosina Quinase AxlRESUMO
Dengue fever is a mosquito-borne disease caused by the dengue virus. Aedes aegypti (Ae. Aegypti) is considered the primary vector of Dengue virus transmission in Yunnan Province, China. With increased urbanization, Ae. aegypti populations have significantly increased over the last 20 years. Despite all the efforts that were made for controlling the virus transmission, especially on border areas between Yunnan and Laos, Vietnam, and Myanmar (dengue-endemic areas), the epidemic has not yet been eradicated. Thus, further understanding of the genetic diversity, population structure, and invasive strategies of Ae. aegypti populations in the border areas was vital to uncover the vector invasion and distribution dynamic, and essential for controlling the infection. In this study, we analyzed genetic diversity and population structure of eight adult Ae. Aegypti populations collected along the border areas of Yunnan Province in 2017 and 2018. Nine nuclear microsatellite loci and mitochondrial DNA (mtDNA) sequences were used to achieve a better understanding of the genetic diversity and population structure. One hundred and fourteen alleles were found in total. The polymorphic information content value, together with the expected heterozygosity (He) and observed heterozygosity (Ho) values showed high genetic diversity in all mosquito populations. The clustering analysis based on Bayesian algorithm, the UPGMA and DAPC analysis revealed that all the eight Ae. aegypti populations can be divided into three genetic groups. Based on the mtDNA results, all Ae. aegypti individuals were divided into 11 haplotypes. The Ae. aegypti populations in the border areas of Yunnan Province presented with high genetic diversity, which might be ascribed to the continuous incursion of Ae. aegypti.
Assuntos
Aedes/classificação , Dengue/prevenção & controle , Repetições de Microssatélites , Análise de Sequência de DNA/veterinária , Aedes/genética , Aedes/virologia , Animais , Teorema de Bayes , DNA Mitocondrial/genética , Doenças Endêmicas/prevenção & controle , Variação Genética , Haplótipos , Controle de Insetos , Laos , Mosquitos Vetores/genética , Mosquitos Vetores/virologia , Mianmar , Filogenia , VietnãRESUMO
The Japanese encephalitis virus (JEV) is a Culex mosquito-borne flavivirus and is the pathogenic agent of Japanese encephalitis, which is the most important type of viral encephalitis in the world. Macrophages are a type of pivotal innate immunocyte that serve as sentinels and respond quickly to pathogen invasions. However, some viruses like JEV can hijack macrophages as a refuge for viral replication and immune escape. Despite their crucial involvement in early JEV infection, the transcriptomic landscapes of JEV-infected macrophages are void. Here, by using an in situ JEV infection model, we investigate the transcriptomic alteration of JEV-infected peritoneal macrophages. We found that, upon JEV infection, the macrophages underwent M1 polarization and showed the drastic activation of innate immune and inflammatory pathways. Interestingly, almost all the programmed cell death (PCD) pathways were activated, especially the apoptosis, pyroptosis, and necroptosis pathways, which were verified by the immunofluorescent staining of specific markers. Further transcriptomic analysis and TUNEL staining revealed that JEV infection caused apparent DNA damage. The transcriptomic analysis also revealed that JEV infection promoted ROS and RNS generation and caused oxidative stress, which activated multiple cell death pathways. Our work uncovers the pivotal pathogenic roles of oxidative stress and multiple PCD pathways in JEV infection, providing a novel perspective on JEV-host interactions.
Assuntos
Apoptose/genética , Vírus da Encefalite Japonesa (Espécie)/fisiologia , Encefalite Japonesa/genética , Encefalite Japonesa/virologia , Perfilação da Expressão Gênica , Macrófagos/metabolismo , Macrófagos/virologia , Transcriptoma , Animais , Dano ao DNA , Encefalite Japonesa/metabolismo , Feminino , Ativação de Macrófagos/genética , Camundongos , Estresse Oxidativo , Carga ViralRESUMO
BACKGROUND: Adverse childhood experiences (ACEs) have been linked to long-term health outcomes, while the impact of such experience has not been investigated among Zambian youth. This study examined the associations of ACEs with individual and clusters of health risk behavior among college students in Zambia. METHOD: A total of 624 college students participated in this cross-sectional study. A self-administered questionnaire was used to collect information on their ACEs and health risk behaviors. RESULTS: There were 58.3% (364) reporting some forms of ACEs, with 27.6% (172), 16.3% (102), and 14.4% (90) being exposed to 1, 2, and ≥ 3 ACEs, respectively. The prevalence of health risk behaviors ranged from 6.0 to 34.2%. Overall, ACEs were associated with increased risk of smoking, binge drinking, suicide attempt, risky sexual behaviors, and illicit drug use. Logistic regression suggested that participants with ≥ 3 ACEs (OR, 3.62; 95% CI, 2.14-6.13) were more likely to engage in the unhealthy cluster, characterized by the presence of any health risk behavior, than those without ACE. CONCLUSION: ACEs were associated with individual and clustering of health risk behaviors among Zambia college students. Our study suggests that early intervention is needed to prevent long-term adverse health consequences in this population.