Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.447
Filtrar
1.
Afr Health Sci ; 19(2): 1988-1992, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31656481

RESUMO

Background: Previous trials have investigated the effect of hepatitis C on lung functions; however, the role of viral load levels is unclear. The aim of this study was to investigate the effect of HCV viremia status on lung functions. Methods: This study was in 60 patients with chronic hepatitis C (CHC). Patients were classified into three groups (non-viremic, low-viremic and high-viremic) based on serum HCV RNA levels. Spirometric parameters (FEV1, FVC, FEV1/FVC) and the proportion of patients with spirometric abnormalities were compared between three groups. Results: High-viremic and low-viremic patients showed a significantly higher prevalance of spirometric abnormality than observed in non-viremic patients (p=0.02). Moreover, there was a significant moderate correlation between viremia level and the percentage of spirometric abnormalities (Cramer's U value=0.452, p=0.002). High-viremic patients were 14.2 times more likely to exhibiting pulmonary dysfunction than non-viremic patients. Additionally, spirometric parameters FEV1 and FVC were significantly reduced in high-viremic and low-viremic patients compared to those in non-viremic patients (p=0.013 and p<0.001 respectively). Conclusion: These results indicate that persistent HCV infection may be associated with reduced pulmonary functions, especially in patients with high viremia levels. Therefore, these patients should be carefully monitored for lung function.


Assuntos
Hepacivirus/isolamento & purificação , Anticorpos Anti-Hepatite C/análise , Hepatite C Crônica/diagnóstico , Pulmão/fisiologia , RNA Viral/sangue , Viremia/diagnóstico , Adulto , Feminino , Hepatite C Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Testes de Função Respiratória , Espirometria , Carga Viral , Viremia/epidemiologia , Viremia/virologia
3.
Science ; 365(6457): 1025-1029, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31488688

RESUMO

Treatment of SIV-infected rhesus macaques with short-term antiretroviral therapy (ART) and partially overlapping infusions of antibody to integrin α4ß7 was reported to induce durable posttreatment viral suppression. In an attempt to replicate those observations, we treated macaques infected with the same virus and with the same ART and monoclonal antibody (mAb) regimens (anti-α4ß7 versus control mAb). Sequencing demonstrated that the virus used was actually SIVmac239-nef-stop, not wild-type SIVmac239. A positive correlation was found at 2 weeks after infection between the frequency of repair of attenuated Nef-STOP virus to pathogenic Nef-OPEN and plasma SIV RNA levels. Levels of plasma viremia before the first antibody infusion and preinfection levels of α4ß7 hi CD4+ T cells, but not treatment with antibody to α4ß7 , correlated with levels of viral replication upon discontinuation of all treatments. Follow-up plasma viremia, peripheral blood CD4+ T cell counts, and lymph node and rectal tissue viral load were not significantly different between anti-α4ß7 and control mAb groups.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Infecções por HIV/terapia , Integrina alfa4/imunologia , Cadeias beta de Integrinas/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/terapia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/imunologia , Animais , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Códon de Terminação , Linfonodos/virologia , Macaca mulatta , RNA Viral/sangue , Reto/virologia , Síndrome de Imunodeficiência Adquirida dos Símios/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Vírus da Imunodeficiência Símia/fisiologia , Carga Viral , Proteínas Virais Reguladoras e Acessórias/genética , Proteínas Virais Reguladoras e Acessórias/imunologia , Viremia/sangue , Viremia/imunologia , Viremia/terapia , Viremia/virologia , Replicação Viral
4.
Transplant Proc ; 51(6): 1801-1809, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399166

RESUMO

BK viremia (BKV) is a recognized and potentially serious problem in renal transplantation. The risk factors and the impact of BKV on renal allograft and patient survival are controversial. This study reports an 8-year, single-center experience on the prevalence, risk factors, and outcomes of BKV in kidney transplant recipients. This is a retrospective analysis of all patients who received a kidney transplant at the University of Kentucky and had BK viral titers available from 2009 to 2017. BKV was defined by a polymerase chain reaction viral load of ≥ 10,000 copies per mL. Demographic, clinical, and laboratory data generated during routine outpatient follow up and inpatients records were collected. Independent risk factors for BKV were determined using uni- and multivariate analysis. Graft and patient survival was compared using Kaplan-Meier analysis, and the severity of polyomavirus nephropathy on biopsy was scored using the Banff 2017 classification. We identified 122 BK positive (19%) and 527 BK negative (81%) patients. BKV developed after a median of 115 days (range, 80-249 days) following kidney transplantation. The 1-, 5-, and 10-year graft survival was 97%, 75%, and 33% in the BKV group and 96%, 85%, and 71% in the BK negative group, respectively. Likewise, the 1-, 5-, and 10-year patient survival was 98%, 84%, and 52% in the BKV group and 98%, 92%, and 84% in the BK negative group. Male sex, age at transplantation, maintenance steroids, and alemtuzumab induction were associated with developing BKV in the multivariate analysis. We concluded that BKV is not uncommon after renal transplantation. The determinants for BKV are male sex, older transplant recipients, and maintenance steroids. BKV adversely affected graft and patient survival. A unified approach for BKV and polyomavirus nephropathy treatment is needed.


Assuntos
Vírus BK , Nefropatias/virologia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/virologia , Complicações Pós-Operatórias/virologia , Infecções Tumorais por Vírus/virologia , Viremia/virologia , Adulto , Biópsia , Feminino , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Rim/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Carga Viral
5.
J Korean Med Sci ; 34(30): e203, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31373185

RESUMO

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is one of the major complications of organ transplantation, especially in children with Epstein-Barr virus (EBV) viremia (EV). We performed a retrospective study to evaluate risk factors for PTLD in children with EV. METHODS: Among 199 pediatric kidney transplantation (KT) recipients at our center from January 2001 to October 2015, records of those with EBV viral loads of > 1,000 copies/mL and/or PTLD were reviewed. RESULTS: Diagnosis of PTLD was made in seven patients (PTLD group), and 39 patients had EV only (EV only group). The median time from KT to EV and PTLD diagnosis was 6.7 (range 0.4-47.8) months and 8.2 (range, 2.8-98.9) months, respectively. There were no significant differences between the groups in terms of sex, age at transplantation, donor type, EBV viral load, or EV-free duration after KT. Higher tacrolimus level before EV (hazard ratio, 44.5; P = 0.003) was an independent risk factor for PTLD in multivariate Cox regression analysis. Six patients with a high EBV load (median 171,639 copies/mL) were treated with preemptive rituximab (RTX) therapy, resulting in transient reduction of EBV load. None of these patients developed PTLD (median follow-up 51.5 months); however, two had neutropenia and two developed infection requiring hospital admission. CONCLUSION: In pediatric KT recipients, higher tacrolimus levels were associated with a higher incidence of PTLD. Conversely, those who received preemptive RTX for EV did not develop PTLD.


Assuntos
Herpesvirus Humano 4/isolamento & purificação , Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/terapia , Viremia/etiologia , Antineoplásicos Imunológicos/uso terapêutico , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neutropenia/etiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Rituximab/uso terapêutico , Transplante Homólogo , Carga Viral , Viremia/tratamento farmacológico , Viremia/virologia
6.
PLoS Comput Biol ; 15(7): e1007229, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31339888

RESUMO

Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. Suspension of therapy is followed by rebound of viral loads to high, pre-therapy levels. However, there is significant heterogeneity in speed of rebound, with some rebounds occurring within days, weeks, or sometimes years. We present a stochastic mathematical model to gain insight into these post-treatment dynamics, specifically characterizing the dynamics of short term viral rebounds (≤ 60 days). Li et al. (2016) report that the size of the expressed HIV reservoir, i.e., cell-associated HIV RNA levels, and drug regimen correlate with the time between ART suspension and viral rebound to detectable levels. We incorporate this information and viral rebound times to parametrize our model. We then investigate insights offered by our model into the underlying dynamics of the latent reservoir. In particular, we refine previous estimates of viral recrudescence after ART interruption by accounting for heterogeneity in infection rebound dynamics, and determine a recrudescence rate of once every 2-4 days. Our parametrized model can be used to aid in design of clinical trials to study viral dynamics following analytic treatment interruption. We show how to derive informative personalized testing frequencies from our model and offer a proof-of-concept example. Our results represent first steps towards a model that can make predictions on a person living with HIV (PLWH)'s rebound time distribution based on biomarkers, and help identify PLWH with long viral rebound delays.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Modelos Biológicos , Algoritmos , Biomarcadores/sangue , Biologia Computacional , Infecções por HIV/imunologia , Humanos , Funções Verossimilhança , RNA Viral/sangue , Processos Estocásticos , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/virologia , Fatores de Tempo , Carga Viral/efeitos dos fármacos , Viremia/tratamento farmacológico , Viremia/imunologia , Viremia/virologia , Latência Viral/efeitos dos fármacos , Latência Viral/imunologia , Suspensão de Tratamento
7.
BMC Infect Dis ; 19(1): 588, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277590

RESUMO

BACKGROUND: HIV controllers (HICs) are a rare group of HIV-1-infected individuals able to naturally control viral replication. Several studies have identified the occurrence of HIV dual infections in seropositive individuals leading to disease progression. In HICs, however, dual infections with divergent outcomes in pathogenesis have been described. CASE PRESENTATION: Here, we present a case report of a HIC diagnosed in late 1999 who displayed stable CD4+ T cell levels and low plasmatic viral load across 12 years of follow-up. In early 2013, the patient started to present an increase in viral load, reaching a peak of 10,000 copies/ml in early 2014, followed by an oscillation of viremia at moderate levels in the following years. The genetic diversity of env proviral quasispecies from peripheral blood mononuclear cells (PBMCs) was studied by single genome amplification (SGA) at six timepoints across 2009-2017. Phylogenetic analyses of env sequences from 2009 and 2010 samples showed the presence of a single subtype B variant (called B1). Analyses of sequences from 2011 and after revealed an additional subtype B variant (called B2) and a subsequent dominance shift in the proviral quasispecies frequencies, with the B2 variant becoming the most frequent from 2014 onwards. Latent syphilis related to unprotected sexual intercourse was diagnosed a year before the first detection of B2, evidencing risk behavior and supporting the superinfection hypothesis. Immunologic analyses revealed an increase in CD8+ and CD4+ T cell immune activation following viremia increase and minor T cell subset alterations during follow-up. HIV-specific T cell responses remained low throughout the follow-up period. CONCLUSIONS: Altogether, these results show that loss of viremia control in the HIC was associated with superinfection. These data alert to the negative consequences of reinfection on HIV pathogenesis, even in patients with a long history of viremia control and an absence of disease progression, reinforcing the need for continued use of adequate prevention strategies.


Assuntos
Infecções por HIV/virologia , HIV-1/fisiologia , Superinfecção/virologia , Replicação Viral/fisiologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , HIV-1/patogenicidade , Antígenos HLA-B/genética , Humanos , Leucócitos Mononucleares/virologia , Masculino , Filogenia , RNA Viral/sangue , Sífilis/diagnóstico , Carga Viral , Viremia/tratamento farmacológico , Viremia/virologia
8.
Cardiol Rev ; 27(4): 179-181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31180937

RESUMO

Multiple strategies have been implemented to increase the donor pool to avoid transplant wait-list mortality. The approval of highly effective direct-acting antiviral regimens for the treatment of hepatitis C virus (HCV) has enabled expansion of the donor pool by allowing the transplantation of organs from HCV-viremic donors to HCV-negative recipients. Multiple centers have recently published data on outcomes of heart transplantation from HCV-viremic heart donors to HCV-negative recipients, with acceptable posttransplant outcomes. However, areas of uncertainty remain, particularly in the long-term risks of intentional HCV transmission, as well as the possibility that sustained virologic response may not be achieved. In this article, we review the literature illustrating both the risks and benefits of transplantation of organs from HCV-viremic donors to HCV-negative recipients. We also present the data collected at our institution regarding this special patient population.


Assuntos
Transplante de Coração/métodos , Hepacivirus , Hepatite C/cirurgia , Doadores de Tecidos , Transplantados , Viremia/cirurgia , Hepatite C/virologia , Humanos , Prognóstico , Viremia/virologia
9.
Transbound Emerg Dis ; 66(4): 1454-1461, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059197

RESUMO

PCV2 is globally spread pathogen involved in a number of diseases (PCVD). Commonly used vaccines against PCV2 are proved to be highly efficacious. The role of recently discovered PCV3 for pig health and interference with PCV2 remains unknown. The study performed on serum samples from seven farms vaccinated against PCV2 and four non-vaccinated showed very low prevalence of PCV2 viremia in the former (3 out of 106 positive serum pools) and high prevalence of PCV2 viremia in the latter (35 out of 60 positive pools). Mean log10 PCV2 genome equivalents were lower in vaccinated farms (4.8 ± 0.6 log10  copies/ml) than in non-vaccinated farms (6.3 ± 1.3 log10  copies/ml). PCV3 was detected in 31 out of 106 and 12 out of 60 serum pools from vaccinated and non-vaccinated farms, respectively. Mean log10 PCV3 genome equivalents were significantly (p < 0.05) lower in vaccinated farms (3.9 ± 0.8 log10  copies/ml) than in non-vaccinated farms (4.4 ± 0.6 log10  copies/ml). Concurrent PCV2 and PCV3 infection was rare and found only in 1 out of 529 and 4 out of 292 individual serum samples from vaccinated and non-vaccinated farms, respectively. Our results showed lack of impact of PCV3 circulation on PCV2 vaccine efficacy. On the other hand, intensive PCV2 circulation and high viremia detected in non-vaccinated farms did not seem to increase the level of PCV3 infection.


Assuntos
Infecções por Circoviridae/veterinária , Circovirus/imunologia , Doenças dos Suínos/prevenção & controle , Vacinas Virais/imunologia , Viremia/veterinária , Animais , Infecções por Circoviridae/prevenção & controle , Infecções por Circoviridae/virologia , Feminino , Reação em Cadeia da Polimerase/veterinária , Suínos , Doenças dos Suínos/virologia , Viremia/prevenção & controle , Viremia/virologia
10.
PLoS Pathog ; 15(5): e1007776, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31083697

RESUMO

VRC01 protects macaques from vaginal SHIV infection after a single high-dose challenge. Infusion of a simianized anti-α4ß7 mAb (Rh-α4ß7) just prior to, and during repeated vaginal exposures to SIVmac251 partially protected macaques from vaginal SIV infection and rescued CD4+ T cells. To investigate the impact of combining VRC01 and Rh-α4ß7 on SHIV infection, 3 groups of macaques were treated with a suboptimal dosing of VRC01 alone or in combination with Rh-α4ß7 or with control antibodies prior to the initiation of weekly vaginal exposures to a high dose (1000 TCID50) of SHIVAD8-EO. The combination Rh-α4ß7-VRC01 significantly delayed SHIVAD8-EO vaginal infection. Following infection, VRC01-Rh-α4ß7-treated macaques maintained higher CD4+ T cell counts and exhibited lower rectal SIV-DNA loads compared to controls. Interestingly, VRC01-Rh-α4ß7-treated macaques had fewer IL-17-producing cells in the blood and the gut during the acute phase of infection. Moreover, higher T cell responses to the V2-loop of the SHIVAD8-EO envelope in the VRC01-Rh-α4ß7 group inversely correlated with set point viremia. The combination of suboptimal amounts of VRC01 and Rh-α4ß7 delayed infection, altered antiviral immune responses and minimized CD4+ T cell loss. Further exploration of the effect of combining bNAbs with Rh-α4ß7 on SIV/HIV infection and antiviral immune responses is warranted and may lead to novel preventive and therapeutic strategies.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais/farmacologia , Integrinas/antagonistas & inibidores , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vagina/efeitos dos fármacos , Viremia/prevenção & controle , Animais , Anticorpos Antivirais/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Quimioterapia Combinada , Feminino , Anticorpos Anti-HIV , Integrinas/imunologia , Macaca mulatta , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/imunologia , Vagina/imunologia , Vagina/virologia , Viremia/imunologia , Viremia/virologia
11.
PLoS Pathog ; 15(4): e1007721, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31009499

RESUMO

The need for improved dengue vaccines remains since the only licensed vaccine, Dengvaxia, shows variable efficacy depending on the infecting dengue virus (DENV) type, and increases the risk of hospitalization for severe dengue in children not exposed to DENV before vaccination. Here, we developed a tetravalent dengue purified and inactivated vaccine (DPIV) candidate and characterized, in rhesus macaques, its immunogenicity and efficacy to control DENV infection by analyzing, after challenge, both viral replication and changes in biological markers associated with dengue in humans. Although DPIV elicited cross-type and long-lasting DENV-neutralizing antibody responses, it failed to control DENV infection. Increased levels of viremia/RNAemia (correlating with serum capacity at enhancing DENV infection in vitro), AST, IL-10, IL-18 and IFN-γ, and decreased levels of IL-12 were detected in some vaccinated compared to non-vaccinated monkeys, indicating the vaccination may have triggered antibody-dependent enhancement of DENV infection. The dengue macaque model has been considered imperfect due to the lack of DENV-associated clinical signs. However, here we show that post-vaccination enhanced DENV infection can be detected in this model when integrating several parameters, including characterization of DENV-enhancing antibodies, viremia/RNAemia, and biomarkers relevant to dengue in humans. This improved dengue macaque model may be crucial for early assessment of efficacy and safety of future dengue vaccines.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Dengue/imunologia , Vacinas de Produtos Inativados/imunologia , Viremia/imunologia , Animais , Anticorpos Facilitadores , Dengue/prevenção & controle , Dengue/virologia , Vacinas contra Dengue/administração & dosagem , Modelos Animais de Doenças , Feminino , Macaca mulatta , Masculino , Vacinação , Viremia/virologia
12.
Poult Sci ; 98(9): 3533-3538, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31002116

RESUMO

Avian leukosis virus subgroup J (ALV-J) belongs to α-retrovirus genus of retroviridae, causing neoplastic disease, immunosuppression, and other problems in the poultry industry worldwide. The aim of this study was to determine whether the reproductive hormone fluctuation affect the ALV-J viremia at the early egg-laying phase in chicken. Total 8 suspected ALV-J-infected Chinese yellow chickens in the early egg-laying phase were collected from 2 different farms, and further confirmed by PCR and immunofluorescence assay. Plasma samples were collected from experimental chickens for 5 to 10 consecutive weeks at a settled time in each week. ALV-J viremia and reproductive hormone levels were monitored by ELISA or radioimmunoassay. The results showed that fluctuations in luteinizing hormone (LH), follicle stimulating hormone (FSH), and progesterone might have an impact on the disappearance of ALV-J viremia in chickens with intermittent viremia, but not in chickens with persistent viremia. These results suggest that reproductive hormone changes during the early egg-laying phase will affect the detection of positive ALV-J-infected chickens in the ALV-J eradication procedures.


Assuntos
Leucose Aviária/virologia , Galinhas/metabolismo , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Doenças das Aves Domésticas/virologia , Progesterona/sangue , Viremia/veterinária , Animais , Leucose Aviária/metabolismo , Vírus da Leucose Aviária/fisiologia , Feminino , Doenças das Aves Domésticas/metabolismo , Viremia/metabolismo , Viremia/virologia
13.
J Infect Chemother ; 25(10): 820-824, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31027885

RESUMO

The BK virus (BKV) is a member of the polyomaviridae family of DNA viruses. BKV reactivates under a highly immunosuppressed state and causes renal dysfunction. In renal transplant patients, BKV infection leads to tubular impairment and loss of transplanted kidney grafts. However, few studies have reported on the relationship between BKV and lung transplantation. Adjustment of the dosage of immunosuppressants is needed in some cases, but the treatment method has not been established. Here, we report a case of BKV-associated viruria and viremia in a patient with lymphangioleiomyomatosis (LAM) after lung re-transplantation. A 44-year-old female refractory LAM patient who had undergone lung re-transplantation 3 months earlier was diagnosed with BKV-associated viruria and viremia. Urine cytology indicated decoy cells and the urine and serum polymerase chain reaction test was positive for BKV. As scheduled after re-transplantation surgery, immunosuppressive drugs were progressively reduced. This patient was considered to have experienced spontaneous BKV-associated viremia and viruria. Review of the literature suggested that 17%-42% of BKV-associated viruria cases have been reported after lung transplantation, but cases of BKV-associated nephropathy are rarely reported. Based on the present case, doctors involved in lung transplantation should monitor patients for BKV infection. Decoy cell monitoring by urine cytology is a useful screening method in the follow-up observation after lung transplantation. Early-stage interventions may prevent BKV-associated nephropathy even in patients who have developed BKV viremia, and sirolimus can be administered to patients with histories of BKV infection if they are carefully monitored.


Assuntos
Vírus BK/isolamento & purificação , Transplante de Pulmão/efeitos adversos , Infecções Urinárias/diagnóstico , Viremia/diagnóstico , Adulto , Vírus BK/imunologia , DNA Viral/isolamento & purificação , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/cirurgia , Linfangioleiomiomatose/imunologia , Linfangioleiomiomatose/cirurgia , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/cirurgia , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/virologia , Reoperação/efeitos adversos , Fatores de Risco , Infecções Tumorais por Vírus/diagnóstico , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologia , Infecções Urinárias/imunologia , Infecções Urinárias/virologia , Carga Viral , Viremia/imunologia , Viremia/virologia
14.
J Acquir Immune Defic Syndr ; 81(1): 118-124, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30964806

RESUMO

BACKGROUND: We evaluated the association between maternal cytomegalovirus (CMV) viremia during pregnancy and adverse birth and infant health outcomes in HIV-infected mothers and their HIV-exposed uninfected infants. METHODS: HIV-positive women and their infants were followed prospectively from pregnancy through 2 years postpartum in the "Tshipidi" study in Botswana. We analyzed the association between detectable CMV DNA in maternal blood at delivery and adverse birth outcomes (stillbirth, preterm delivery, small for gestational age, or birth defect), as well as infant hospitalization and mortality through 24 months. RESULTS: We measured CMV DNA in blood samples from 350 (77.1%) of 454 HIV-positive women from the Tshipidi study. The median maternal CD4 count was 422 cells/mL, and median HIV-1 RNA at entry was 3.2 log10 copies/mL. Fifty-one (14.6%) women had detectable CMV DNA. In unadjusted analyses, detectable CMV DNA was associated with higher maternal HIV-1 RNA [odds ratio (OR) 1.4, 95% confidence interval (CI): 1.1 to 1.9], presence of a birth defect (OR 9.8, 95% CI: 1.6 to 60.3), and occurrence of any adverse birth outcome (OR 2.0, 95% CI: 1.04 to 3.95). In multivariable analysis, we observed a trend toward association between detectable maternal CMV DNA and occurrence of any adverse birth outcome (adjusted OR 1.9, 95% CI: 0.96 to 3.8). Maternal CMV viremia was not associated with infant hospitalization and/or death by 24 months. CONCLUSIONS: Approximately 1 in 6 HIV-positive women in Botswana had detectable CMV DNA in blood at delivery. The presence of maternal CMV viremia had a borderline association with adverse birth outcomes but not with 24-month morbidity or mortality in HIV-exposed uninfected children.


Assuntos
Coinfecção/complicações , Infecções por Citomegalovirus/complicações , Infecções por HIV/complicações , HIV-1 , Viremia/complicações , Adulto , Botsuana , Coinfecção/virologia , Infecções por Citomegalovirus/virologia , Parto Obstétrico/estatística & dados numéricos , Feminino , Infecções por HIV/virologia , Humanos , Lactente , Mortalidade Infantil , Gravidez , Resultado da Gravidez , Viremia/virologia , Adulto Jovem
15.
Virology ; 531: 219-232, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30928700

RESUMO

Equid herpesvirus-1 (EHV-1) outbreaks continue despite widely used vaccination. We demonstrated previously that an ORF1/ORF71 gene deletion mutant of the EHV-1 strain Ab4 (Ab4ΔORF1/71) is less virulent than its parent Ab4 virus. Here, we describe the Ab4 challenge infection evaluating protection induced by the Ab4ΔORF1/71 vaccine candidate. Susceptible control horses developed respiratory disease, fever, nasal shedding, and viremia. Full protection after challenge infection was observed in 5/5 previously Ab4 infected horses and 3/5 Ab4ΔORF1/71 horses. Two Ab4ΔORF1/71 horses developed short-lasting viremia and/or virus shedding. Protective immunity in the respiratory tract was characterized by pre-existing EHV-1-specific IgG4/7 antibodies, the absence of IFN-α secretion and rapidly increasing IgG4/7 upon challenge infection. Pre-existing systemic EHV-1-specific IgG4/7 highly correlated with protection. T-cell immunity was overall low. In conclusion, protective immunity against EHV-1 infection including prevention of viremia was associated with robust systemic and intranasal IgG4/7 antibodies suggesting immediate virus neutralization at the local site.


Assuntos
Anticorpos Antivirais/imunologia , Infecções por Herpesviridae/veterinária , Herpesvirus Equídeo 1/imunologia , Vacinas contra Herpesvirus/administração & dosagem , Doenças dos Cavalos/prevenção & controle , Imunoglobulina G/imunologia , Viremia/veterinária , Administração Intranasal , Animais , Feminino , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/prevenção & controle , Infecções por Herpesviridae/virologia , Herpesvirus Equídeo 1/efeitos dos fármacos , Herpesvirus Equídeo 1/genética , Herpesvirus Equídeo 1/fisiologia , Vacinas contra Herpesvirus/imunologia , Doenças dos Cavalos/imunologia , Doenças dos Cavalos/virologia , Cavalos , Masculino , Mucosa Nasal/imunologia , Mucosa Nasal/virologia , Vacinação , Viremia/imunologia , Viremia/prevenção & controle , Viremia/virologia , Eliminação de Partículas Virais
17.
Arab J Gastroenterol ; 20(1): 8-13, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30857834

RESUMO

BACKGROUND AND STUDY AIMS: Mother-infant hepatitis B virus (HBV) transmission is the current leading cause of chronic infection. We aimed to assess the efficacy of lamivudine use in hepatitis B surface antigen (HBsAg)-positive pregnant women to decrease viral load and thus aid in the prevention of transmission. PATIENTS AND METHODS: A study of 73 mother-infant pairs. All mono-infected HBsAg-positive pregnant females of any age, who were a candidate for lamivudine during pregnancy were recruited, and a comparison group of HBsAg-positive pregnant females who did not receive any antiviral treatment. All infants received HBV immunoglobulin and vaccine at birth and completed the vaccination schedule and tested after 6 months of age. HBV viral markers and viral load quantitation were performed to all enrolled participants. RESULTS: 34 (46.6%) females were enrolled in the lamivudine group; 9 (26.5%) received the drug in the last trimester, 25 (73.5%) all through. The comparison group was 39 (53.4%) females; 32 (82.1%) were not candidate for antiviral during pregnancy, and 7 (17.9%) were diagnosed late near delivery. Seventy-one infants tested after full immunization, with their ages ranged between 6.5 and 18 months. Only one infant (1.4%) was positive for HBsAg and HBV DNA in the non-treated group. Maternal viremia near delivery showed a significant reduction in cases that used lamivudine during pregnancy. CONCLUSION: The use of lamivudine during pregnancy can effectively lower maternal viral load. Timely conducted post-vaccination serological testing is crucial to detect positive cases and immunize susceptible infants.


Assuntos
Hepatite B/tratamento farmacológico , Hepatite B/transmissão , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Lamivudina/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , DNA Viral/sangue , Feminino , Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B , Vírus da Hepatite B/genética , Humanos , Imunoglobulinas , Lactente , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/sangue , Estudos Prospectivos , Vacinação , Carga Viral/efeitos dos fármacos , Viremia/tratamento farmacológico , Viremia/virologia , Adulto Jovem
18.
PLoS One ; 14(3): e0213793, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30908528

RESUMO

Dengue virus (DENV) transmission by blood transfusion is an important route of viral acquisition during outbreaks. The prevalence of DENV markers (viral RNA, NS1, anti-DENV IgM, and IgG) among blood donors in Central-West Brazil has never been evaluated. Our aim was to evaluate the full set of serological and molecular markers for DENV among blood donors of the Federal District of Brazil during an extensive outbreak in 2016. We found an anti-DENV IgM prevalence of 6.74% (n = 32/475). Of 475, 20 samples (4.21%) were also anti-DENV IgG positive. All samples were non-reactive for NS1 and DENV RNA. Our results imply that a significant proportion of the tested donors had experienced asymptomatic infection. More studies are necessary to evaluate the real prevalence of DENV viremia in blood donors from the Federal District of Brazil and if specific measures are needed to routinely test the blood donors for DENV RNA during outbreaks.


Assuntos
Anticorpos Antivirais/sangue , Infecções Assintomáticas/epidemiologia , Doadores de Sangue/estatística & dados numéricos , Vírus da Dengue/imunologia , Dengue/imunologia , Surtos de Doenças , Proteínas não Estruturais Virais/imunologia , Adulto , Anticorpos Antivirais/imunologia , Transfusão de Sangue , Brasil/epidemiologia , Estudos de Coortes , Dengue/sangue , Dengue/epidemiologia , Dengue/virologia , Vírus da Dengue/genética , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Projetos Piloto , RNA Viral/genética , Estudos Soroepidemiológicos , Viremia/sangue , Viremia/epidemiologia , Viremia/imunologia , Viremia/virologia
19.
J Neuroinflammation ; 16(1): 22, 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30704498

RESUMO

BACKGROUND: Microglia are resident macrophages of the central nervous system (CNS) locally maintained through colony-stimulating factor 1 receptor (CSF1R) signaling. Microglial depletion via CSF1R inactivation improves cognition in mouse models of neuroinflammation, but limits virologic control in the CNS of mouse models of neurotropic infections by unknown mechanisms. We hypothesize that CSF1R plays a critical role in myeloid cell responses that restrict viral replication and locally restimulate recruited antiviral T cells within the CNS. METHODS: The impact of CSF1R signaling during West Nile virus infection was assessed in vivo using a mouse model of neurotropic infection. Pharmacological inactivation of CSF1R was achieved using PLX5622 prior to infection with virulent or attenuated strains of West Nile virus (WNV), an emerging neuropathogen. The subsequent effect of CSF1R antagonism on virologic control was assessed by measuring mortality and viral titers in the CNS and peripheral organs. Immune responses were assessed by flow cytometric-based phenotypic analyses of both peripheral and CNS immune cells. RESULTS: Mice treated with CSF1R antagonist prior to infection exhibited higher susceptibility to lethal WNV infection and lack of virologic control in both the CNS and periphery. CSFR1 antagonism reduced B7 co-stimulatory signals on peripheral and CNS antigen-presenting cells (APCs) by depleting CNS cellular sources, which limited local reactivation of CNS-infiltrating virus-specific T cells and reduced viral clearance. CONCLUSIONS: Our results demonstrate the impact of CSF1R antagonism on APC activation in the CNS and periphery and the importance of microglia in orchestrating the CNS immune response following neurotropic viral infection. These data will be an important consideration when assessing the benefit of CSF1R antagonism, which has been investigated as a therapeutic for neurodegenerative conditions, in which neuroinflammation is a contributing factor.


Assuntos
Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/virologia , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Febre do Nilo Ocidental/virologia , Animais , Antivirais , Linfócitos T CD8-Positivos/imunologia , Imunidade Celular/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/virologia , Compostos Orgânicos/farmacologia , Carga Viral , Viremia/virologia , Febre do Nilo Ocidental/imunologia
20.
J Virol ; 93(8)2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30728253

RESUMO

Animal models of Zika virus (ZIKV) infection have recently been established in mice, guinea pigs, and nonhuman primates. Tree shrews (Tupaia belangeri) are an emerging experimental animal in biomedical applications, but their susceptibility to ZIKV infection has not been explored. In the present study, we show that subcutaneous inoculation of ZIKV led to rapid viremia and viral secretion in saliva, as well as to typical dermatological manifestations characterized by massive diffuse skin rash on the trunk. Global transcriptomic sequencing of peripheral blood mononuclear cells isolated from ZIKV-infected animals revealed systematic gene expression changes related to the inflammatory response and dermatological manifestations. Importantly, ZIKV infection readily triggered the production of high-titer neutralizing antibodies, thus preventing secondary homologous infection in tree shrews. However, neonatal tree shrews succumbed to ZIKV challenge upon intracerebral infection. The tree shrew model described here recapitulates the most common dermatological manifestations observed in ZIKV-infected patients and may greatly facilitate the elucidation of ZIKV pathogenesis and the development of novel vaccines and therapeutics.IMPORTANCE The reemergence of Zika virus (ZIKV) has caused a global public health crisis since 2016, and there are currently no vaccines or antiviral drugs to prevent or treat ZIKV infection. However, considerable advances have been made in understanding the biology and pathogenesis of ZIKV infection. In particular, various animal models have been successfully established to mimic ZIKV infection and its associated neurological diseases and to evaluate potential countermeasures. However, the clinical symptoms in these mouse and nonhuman primate models are different from the common clinical manifestations seen in human ZIKV patients; in particular, dermatological manifestations are rarely recapitulated in these animal models. Here, we developed a new animal model of ZIKV infection in tree shrews, a rat-sized, primate-related mammal. In vitro and in vivo characterization of ZIKV infection in tree shrews established a direct link between ZIKV infection and the immune responses and dermatological manifestations. The tree shrew model described here, as well as other available animal models, provides a valuable platform to study ZIKV pathogenesis and to evaluate vaccines and therapeutics.


Assuntos
Dermatopatias Virais , Tupaia , Infecção por Zika virus , Zika virus/metabolismo , Animais , Linhagem Celular , Cricetinae , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/veterinária , Inflamação/virologia , Masculino , Saliva/metabolismo , Saliva/virologia , Dermatopatias Virais/metabolismo , Dermatopatias Virais/patologia , Dermatopatias Virais/veterinária , Dermatopatias Virais/virologia , Tupaia/metabolismo , Tupaia/virologia , Viremia/metabolismo , Viremia/patologia , Viremia/virologia , Infecção por Zika virus/metabolismo , Infecção por Zika virus/patologia , Infecção por Zika virus/veterinária
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA