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1.
Arch Virol ; 166(5): 1345-1353, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33689039

RESUMO

Human pegivirus 1 (HPgV-1) belongs to the genus Pegivirus, family Flaviviridae, and until now has been considered a non-pathogenic agent, despite being considered a risk factor for non-Hodgkin lymphoma. However, a beneficial impact of HPgV-1 on HIV disease progression has been extensively reported. Given the high prevalence of HIV in sub-Saharan Africa and the scarcity of epidemiological data for many countries of West Africa, we conducted the first study of HPgV-1 in HIV-infected individuals from Cabo Verde. To obtain new data regarding prevalence and genetic diversity of HPgV-1 in Africa, serum samples from 102 HIV-infected Cabo Verdeans were tested for the presence of viral RNA, and the circulating genotypes were identified by sequencing of the 5' untranslated region. HPgV-1 RNA was detected in 19.6% (20/102) of the samples. In 72.2% (13/18) of the samples, the virus was identified as genotype 2 (11/13 subtype 2a and 2/13 subtype 2b), and in 27.8% (5/18), it was identified as genotype 1. The estimated substitution rate of HPgV-1 genotype 2 was 5.76 × 10-4, and Bayesian analysis indicated the existence of inner clusters within subtypes 2a and 2b. The prevalence of HPgV-1 viremia in Cabo Verde agrees with that reported previously in Africa. Genotypes 1 and 2 cocirculate, with genotype 2 being more common, and HIV/HPgV-1 coinfection was not associated with higher CD4 T cell counts in the studied population. This finding contributes for the expansion of the pegivirus research agenda in African countries.


Assuntos
Infecções por Flaviviridae/epidemiologia , Vírus GB C/genética , Infecções por HIV/epidemiologia , Hepatite Viral Humana/epidemiologia , Regiões 5' não Traduzidas/genética , Cabo Verde/epidemiologia , Coinfecção/epidemiologia , Coinfecção/virologia , Infecções por Flaviviridae/virologia , Vírus GB C/classificação , Vírus GB C/isolamento & purificação , Variação Genética , Genótipo , Hepatite Viral Humana/virologia , Humanos , Filogenia , Prevalência , RNA Viral/sangue , RNA Viral/genética , Viremia/epidemiologia , Viremia/virologia
3.
BMC Infect Dis ; 21(1): 213, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632148

RESUMO

BACKGROUND: Previous studies have demonstrated an association between adenovirus viremia and disease severity in immunocompromised children. However, few studies have focused on this association in immunocompetent children. This study explored the association between adenovirus viremia and adenovirus pneumonia severity in immunocompetent children. METHODS: We performed a retrospective, observational study of immunocompetent children with adenovirus pneumonia admitted to Shenzhen Children's Hospital in Shenzhen, China. Pneumonia was classified as severe or mild based on the Chinese guideline for the classification of pneumonia severity. Serum samples from all the children included in the study were tested for adenovirus DNA with a quantitative polymerase chain reaction. Clinical manifestations, laboratory examinations, and disease severity were compared between children with severe and mild pneumonia. RESULTS: A total of 111 immunocompetent children with adenovirus pneumonia (60 severe, 51 mild) were included. The median age was 40 months, and 64 patients were male. Five patients were admitted to the intensive care unit, and two underwent endotracheal intubation. All patients were discharged after recovery or improvement. Univariate analysis and binary logistic regression analysis showed that leukocytosis (OR = 1.1; 95% CI: 1.0 to 1.2; P = 0.033), co-infection with Mycoplasma pneumoniae (OR = 5.0; 95% CI: 2.1 to 12.3; P <  0.001), and high blood viral load (OR = 1.5; 95% CI: 1.2 to 2.0; P = 0.001) may be risk factors for severe adenovirus pneumonia. CONCLUSIONS: Leukocytosis, co-infection with Mycoplasma pneumoniae, and high blood viral load may be risk factors for severe adenovirus pneumonia in immunocompetent children. Blood viral load may predict pneumonia severity.


Assuntos
Adenoviridae/fisiologia , Infecções por Adenovirus Humanos/virologia , Pneumonia Viral/virologia , Viremia/virologia , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Hospitais Pediátricos , Humanos , Lactente , Masculino , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Carga Viral , Viremia/epidemiologia
4.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(2): 316-320, 2021 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-33626622

RESUMO

Objective: To study the prevalence and correlates of plasma cytomegalovirus (CMV) viremia among newly reported antiretroviral therapy (ART)-naive HIV/AIDS patients in Taizhou during 2017-2018. Methods: CMV DNA was measured in plasma specimens of newly reported ART-naive HIV/AIDS patients by quantitative PCR. Both univariable and multivariable logistic regression analyses were carried out to evaluate CMV viremia correlations among the individuals. Results: Of 612 HIV/AIDS patients, 480 (78.4%) were male, 125 (20.4%) were over 60 years old, 177 (28.9%) were infected via homosexual transmission, and 430 (70.3%) via heterosexual transmission. The prevalence of CMV viremia among HIV/AIDS patients was 13.4% (82/612). Multivariable logistic regression analysis showed that the risk of CMV viremia in CD4+ lymphocyte cells counts (CD4+) ≤200 cells/µl group was higher than CD4 counts >500 cells/µl (OR=5.10, 95%CI:1.74-14.96, P=0.003); The median CMV DNA level (log10) of 82 viremic patients was 1.57 (P25,P75:1.04,2.13); Viremic patients with CD4 counts ≤200 cells/µl had the highest CMV viral load (P<0.01). Conclusions: Among ART-naive HIV/AIDS patients, the prevalence of CMV viremia was significantly associated with immunodeficiency status. Further research is needed to evaluate the association between CMV viremia and the course of HIV infection.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Infecções por HIV , Viremia , China/epidemiologia , Cidades/epidemiologia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Viremia/epidemiologia
5.
BMC Infect Dis ; 21(1): 223, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637051

RESUMO

BACKGROUND: Despite a dramatic reduction in HCV drug costs and simplified models of care, many countries lack important information on prevalence and risk factors to structure effective HCV services. METHODS: A cross-sectional, multi-stage cluster survey of HCV seroprevalence in adults 18 years and above was conducted, with an oversampling of those 45 years and above. One hundred forty-seven clusters of 25 households were randomly selected in two sets (set 1=24 clusters ≥18; set 2=123 clusters, ≥45). A multi-variable analysis assessed risk factors for sero-positivity among participants ≥45. The study occurred in rural Moung Ruessei Health Operational District, Battambang Province, Western Cambodia. RESULTS: A total of 5098 individuals and 3616 households participated in the survey. The overall seroprevalence was 2.6% (CI95% 2.3-3.0) for those ≥18 years, 5.1% (CI95% 4.6-5.7) for adults ≥ 45 years, and 0.6% (CI95% 0.3-0.9) for adults 18-44. Viraemic prevalence was 1.9% (CI95% 1.6-2.1), 3.6% (CI95% 3.2-4.0), and 0.5% (CI95% 0.2-0.8), respectively. Men had higher prevalence than women: ≥18 years male seroprevalence was 3.0 (CI95% 2.5-3.5) versus 2.3 (CI95% 1.9-2.7) for women. Knowledge of HCV was poor: 64.7% of all respondents and 57.0% of seropositive participants reported never having heard of HCV. Risk factor characteristics for the population ≥45 years included: advancing age (p< 0.001), low education (higher than secondary school OR 0.7 [95% CI 0.6-0.8]), any dental or gum treatment (OR 1.6 [95% CI 1.3-1.8]), historical routine medical care (medical injection after 1990 OR 0.7 [95% CI 0.6-0.9]; surgery after 1990 OR 0.7 [95% CI0.5-0.9]), and historical blood donation or transfusion (blood donation after 1980 OR 0.4 [95% CI 0.2-0.8]); blood transfusion after 1990 OR 0.7 [95% CI 0.4-1.1]). CONCLUSIONS: This study provides the first large-scale general adult population prevalence data on HCV infection in Cambodia. The results confirm the link between high prevalence and age ≥45 years, lower socio-economic status and past routine medical interventions (particularly those received before 1990 and 1980). This survey suggests high HCV prevalence in certain populations in Cambodia and can be used to guide national and local HCV policy discussion.


Assuntos
Hepacivirus/imunologia , Hepatite C/epidemiologia , Viremia/epidemiologia , Adolescente , Adulto , Idoso , Camboja/epidemiologia , Estudos Transversais , Características da Família , Feminino , Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Estudos Soroepidemiológicos , Viremia/diagnóstico , Viremia/virologia , Adulto Jovem
6.
Dis Aquat Organ ; 143: 169-188, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33629660

RESUMO

Spring viremia of carp virus (SVCV) ia a carp sprivivirus and a member of the genus Sprivivirus within the family Rhabdoviridae. The virus is the etiological agent of spring viremia of carp, a disease of cyprinid species including koi Cyprinus carpio L. and notifiable to the World Organisation for Animal Health. The goal of this study was to explore hypotheses regarding inter-genogroup (Ia to Id) SVCV infection dynamics in juvenile koi and contemporaneously create new reverse-transcription quantitative PCR (RT-qPCR) assays and validate their analytical sensitivity, specificity (ASp) and repeatability for diagnostic detection of SVCV. RT-qPCR diagnostic tests targeting the SVCV nucleoprotein (Q2N) or glycoprotein (Q1G) nucleotides were pan-specific for isolates typed to SVCV genogroups Ia to Id. The Q2N test had broader ASp than Q1G because Q1G did not detect SVCV isolate 20120450 and Q2N displayed occasional detection of pike fry sprivivirus isolate V76. Neither test cross-reacted with other rhabdoviruses, infectious pancreatic necrosis virus or co-localizing cyprinid herpesvirus 3. Both tests were sensitive with observed 50% limits of detection of 3 plasmid copies and high repeatability. Test analysis of koi immersed in SVCV showed that the virus could be detected for at least 167 d following exposure and that titer, prevalence, replicative rate and persistence in koi were correlated significantly with virus virulence. In this context, high virulence SVCV isolates were more prevalent, reached higher titers quicker and persisted in koi for longer periods of time relative to moderate and low virulence isolates.


Assuntos
Carpas , Doenças dos Peixes , Infecções por Rhabdoviridae , Animais , Doenças dos Peixes/diagnóstico , Infecções por Rhabdoviridae/diagnóstico , Infecções por Rhabdoviridae/veterinária , Vesiculovirus , Viremia/veterinária
7.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541971

RESUMO

COVID-19 is a biphasic illness with an initial viraemia phase and later effective adaptive immune phase, except in a minority of people who develop severe disease. Immune regulation is the key target to treat COVID illness. In anticipation, an elderly man self-medicated himself with dexamethasone on the day of symptom onset of a flu-like illness, took other symptomatic measures and was tested positive for SARS-CoV-2. His condition deteriorated with each passing day resulting in hospitalisation. He demanded oxygen and declared as severe COVID. With supportive treatment, he recovered after the 20th day of illness. Immunosuppression and anti-inflammation are likely to benefit when the immune response is dysregulated and turning into a cytokine storm. A medication that has saved many could be the one predisposing to severity if taken as a preventive measure, too early in the disease course, especially the viraemia phase.


Assuntos
Anti-Inflamatórios/efeitos adversos , Dexametasona/efeitos adversos , Viremia/tratamento farmacológico , Idoso , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Hospitalização , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Automedicação/métodos , Esteroides/efeitos adversos , Esteroides/uso terapêutico , Resultado do Tratamento , Viremia/complicações
8.
BMC Infect Dis ; 21(1): 184, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596855

RESUMO

BACKGROUND: Recent studies showed that plasma SARS-CoV-2 RNA seems to be associated with worse COVID-19 outcome. However, whether specific population can be at higher risk of viremia are to date unexplored. METHODS: This cross-sectional proof-of-concept study included 41 SARS-CoV-2-positive adult individuals (six affected by haematological malignancies) hospitalized at two major hospital in Milan, for those demographic, clinical and laboratory data were available. SARS-CoV-2 load was quantified by ddPCR in paired plasma and respiratory samples. To assess significant differences between patients with and patients without viremia, Fisher exact test and Wilcoxon test were used for categorical and continuous variables, respectively. RESULTS: Plasma SARS-CoV-2 RNA was found in 8 patients (19.5%), with a median (IQR) value of 694 (209-1023) copies/mL. Viremic patients were characterized by an higher mortality rate (50.0% vs 9.1%; p = 0.018) respect to patients without viremia. Viremic patients were more frequently affected by haematological malignancies (62.5% vs. 3.0%; p < 0.001), and had higher viral load in respiratory samples (9,404,000 [586,060-10,000,000] vs 1560 [312-25,160] copies/mL; p = 0.002). CONCLUSIONS: Even if based on a small sample population, this proof-of-concept study poses the basis for an early identification of patients at higher risk of SARS-CoV-2 viremia, and therefore likely to develop severe COVID-19, and supports the need of a quantitative viral load determination in blood and respiratory samples of haematologic patients with COVID-19 in order to predict prognosis and consequently to help their further management.


Assuntos
/métodos , /diagnóstico , RNA Viral/sangue , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudo de Prova de Conceito , Testes Sorológicos , Carga Viral , Viremia/virologia
9.
Am J Hematol ; 96(4): 436-445, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33439488

RESUMO

Even in the era of PCR-based monitoring, prophylaxis, and preemptive therapy, Cytomegalovirus (CMV) viremia remains a relevant cause of non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT). However, studies using binary analysis (presence/absence of CMV) reported contradicting data for NRM, overall survival and leukemia relapse. Here, we analyzed CMV replication kinetics in 11 508 whole blood PCR samples of 705 patients with HCT between 2012 and 2017. Using two independent models based on CMV peak titers and on the time point of first CMV reactivation, we stratified patients into risk cohorts. Each cohort had distinct cellular immune reconstitution profiles and differentiated for relevant clinical outcomes. Patients with high CMV peak titers had significantly reduced overall survival (HR 2.13, 95% CI 1.53-2.96; p < .0001), due to high NRM. Early impaired T cell reconstitution was a risk factor for high CMV peak titers, however relevant CMV viremia also related to boosted T cell reconstitution. Importantly, intermediate CMV peak titers associated with a significantly reduced relapse probability (HR 0.53, 95% CI 0.31-0.91; p = .022). In short, CMV kinetics models distinguished relevant clinical outcome cohorts beyond the R+ serostatus with distinct immune reconstitution patterns and resolve in part contradicting results of previous studies exclusively focused on the presence or absence of CMV.


Assuntos
Infecções por Citomegalovirus/virologia , Citomegalovirus/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas , Carga Viral , Viremia/virologia , Adolescente , Adulto , Idoso , Aloenxertos , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/imunologia , Feminino , Seguimentos , Humanos , Reconstituição Imune , Estimativa de Kaplan-Meier , Cinética , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Viremia/imunologia , Ativação Viral , Adulto Jovem
10.
Nature ; 590(7846): 468-472, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33505020

RESUMO

Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies1-3. Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013-2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a 'decay-stimulation-decay' pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77-100 days and a doubling time of 46-86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5-2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak.


Assuntos
Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Convalescença , Ebolavirus/imunologia , Doença pelo Vírus Ebola/imunologia , Sobreviventes , Adolescente , Adulto , África Ocidental/epidemiologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Estudos de Coortes , Feminino , Meia-Vida , Doença pelo Vírus Ebola/sangue , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Fatores de Tempo , Viremia/sangue , Viremia/imunologia , Adulto Jovem
11.
Viruses ; 13(1)2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445523

RESUMO

The extraordinary genetic variability of human immunodeficiency virus type 1 (HIV-1) group M has led to the identification of 10 subtypes, 102 circulating recombinant forms (CRFs) and numerous unique recombinant forms. Among CRFs, 11 derived from subtypes B and C have been identified in China, Brazil, and Italy. Here we identify a new HIV-1 CRF_BC in Northern Spain. Originally, a phylogenetic cluster of 15 viruses of subtype C in protease-reverse transcriptase was identified in an HIV-1 molecular surveillance study in Spain, most of them from individuals from the Basque Country and heterosexually transmitted. Analyses of near full-length genome sequences from six viruses from three cities revealed that they were BC recombinant with coincident mosaic structures different from known CRFs. This allowed the definition of a new HIV-1 CRF designated CRF108_BC, whose genome is predominantly of subtype C, with four short subtype B fragments. Phylogenetic analyses with database sequences supported a Brazilian ancestry of the parental subtype C strain. Coalescent Bayesian analyses estimated the most recent common ancestor of CRF108_BC in the city of Vitoria, Basque Country, around 2000. CRF108_BC is the first CRF_BC identified in Spain and the second in Europe, after CRF60_BC, both phylogenetically related to Brazilian subtype C strains.


Assuntos
Genoma Viral , Genótipo , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Recombinação Genética , Variação Genética , Humanos , Epidemiologia Molecular , Filogenia , Filogeografia , Vigilância em Saúde Pública , Análise de Sequência de DNA , Espanha/epidemiologia , Viremia
12.
Lancet Gastroenterol Hepatol ; 6(3): 169-184, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33515496

RESUMO

BACKGROUND: Treatment for infection with hepatitis C virus (HCV) during pregnancy has not yet been approved; however, interventions specifically targeting women, especially those of childbearing age (15-49 years), could prevent vertical transmission and community spread. To assess the impact of such interventions, improved prevalence estimates in this group are needed. We aimed to estimate the global prevalence of viraemic HCV in 2019 among women of childbearing age. METHODS: In this modelling study, we used previously developed models for 110 countries inputted with country-specific demographic and HCV epidemiology data. We did a literature review, searching PubMed, Embase, and grey literature for studies published between Jan 1, 2000, and June 30, 2018, reporting HCV antibody or viraemic prevalence in women of childbearing age. Studies from the literature review and studies in models were compared by use of a data quality scoring system and models were updated, as appropriate, when a better study was identified. We used these HCV disease burden models to calculate the 2019 prevalence of viraemic HCV in women of childbearing age. In countries without a model, prevalence was extrapolated by Global Burden of Disease (GBD) region. FINDINGS: An estimated 14 860 000 (95% uncertainty interval [UI] 9 667 000-18 282 000) women aged 15-49 years had HCV infection worldwide in 2019, corresponding to a viraemic prevalence of 0·78% (95% UI 0·62-0·86). Globally, HCV prevalence increased with age, rising from 0·25% (95% UI 0·20-0·27) in women aged 15-19 years to 1·21% (0·97-1·34) in women aged 45-49 years. China (16% of total infections) and Pakistan (15%) had the greatest numbers of viraemic infections, but viraemic prevalence was highest in Mongolia (5·14%, 95% CI 3·46-6·28) and Burundi (4·91%, 3·80-18·75). Of the countries with 500 cases or more, viraemic prevalence was lowest in Chile (0·07%, 95% UI 0·04-0·12). Among the GBD regions, eastern Europe had the highest viraemic prevalence (3·39%, 95% UI 1·88-3·54). By WHO region, the Eastern Mediterranean region had the highest viraemic prevalence (1·75%, 95% UI 1·26- 1·90). INTERPRETATION: Most research on HCV disease burden among women aged 15-49 years focuses on pregnant women. Using modelling, this analysis provides global and national estimates of HCV prevalence in all women of childbearing age. These data can inform preconception test-and-treat strategies to reduce vertical transmission and total disease burden. FUNDING: Gilead Sciences, John C Martin Foundation, private donors.


Assuntos
Hepatite C/tratamento farmacológico , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Viremia/epidemiologia , Adolescente , Adulto , Feminino , Carga Global da Doença , Hepacivirus/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Hepatite C/complicações , Hepatite C/epidemiologia , Hepatite C/virologia , Humanos , Pessoa de Meia-Idade , Modelos Teóricos , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Prevalência , Literatura de Revisão como Assunto , Adulto Jovem
14.
Vet Microbiol ; 253: 108958, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33387911

RESUMO

Porcine hemagglutinating encephalomyelitis virus (PHEV) is the cause of acute outbreaks of vomiting and wasting disease and/or encephalomyelitis in neonatal pigs, with naïve herds particularly vulnerable to clinical episodes. PHEV infections in older pigs are generally considered to be subclinical, but are poorly characterized in the refereed literature. In this study, twelve 7-week-old pigs were oronasally inoculated with 0.5 mL (1:128 HA titer) PHEV (Mengeling strain) and then followed through 42 days post inoculation (dpi). Fecal and oral fluid specimens were collected daily to evaluate viral shedding. Serum samples were tested for viremia, isotype-specific antibody responses, cytokine, and chemokine responses. Peripheral blood mononuclear cells were isolated to evaluate phenotype changes in immune cell subpopulations. No clinical signs were observed in PHEV inoculated pigs, but virus was detected in oral fluid (1-28 dpi) and feces (1-10 dpi). No viremia was detected, but a significant IFN-α response was observed in serum at 3 dpi, followed by the detection of IgM (dpi 7), and IgA/IgG (dpi 10). Flow cytometry revealed a one-off increase in cytotoxic T cells at 21 dpi. This study demonstrated that exposure of grower pigs to PHEV results in subclinical infection characterized by active viral replication and shedding followed by an active humoral and cell-mediated immune response that attenuates the course of the infection and results in viral clearance.


Assuntos
Betacoronavirus 1/isolamento & purificação , Infecções por Coronavirus/veterinária , Doenças dos Suínos/virologia , Animais , Anticorpos Antivirais/sangue , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Interferon-alfa/biossíntese , Interferon-alfa/sangue , Suínos , Doenças dos Suínos/sangue , Doenças dos Suínos/imunologia , Viremia
15.
Science ; 371(6525): 190-194, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33414219

RESUMO

There are no approved flaviviral therapies and the development of vaccines against flaviruses has the potential of being undermined by antibody-dependent enhancement (ADE). The flavivirus nonstructural protein 1 (NS1) is a promising vaccine antigen with low ADE risk but has yet to be explored as a broad-spectrum therapeutic antibody target. Here, we provide the structural basis of NS1 antibody cross-reactivity through cocrystallization of the antibody 1G5.3 with NS1 proteins from dengue and Zika viruses. The 1G5.3 antibody blocks multi-flavivirus NS1-mediated cell permeability in disease-relevant cell lines, and therapeutic application of 1G5.3 reduces viremia and improves survival in dengue, Zika, and West Nile virus murine models. Finally, we demonstrate that 1G5.3 protection is independent of effector function, identifying the 1G5.3 epitope as a key site for broad-spectrum antiviral development.


Assuntos
Anticorpos Neutralizantes/química , Anticorpos Antivirais/química , Vírus da Dengue/imunologia , Proteínas não Estruturais Virais/imunologia , Vírus do Nilo Ocidental/imunologia , Zika virus/imunologia , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/uso terapêutico , Células CHO , Linhagem Celular , Cricetulus , Reações Cruzadas , Dengue/prevenção & controle , Dengue/terapia , Modelos Animais de Doenças , Humanos , Camundongos , Domínios Proteicos , Proteínas não Estruturais Virais/química , Viremia/terapia , Febre do Nilo Ocidental/prevenção & controle , Febre do Nilo Ocidental/terapia , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/terapia
16.
Infect Genet Evol ; 88: 104684, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33352320

RESUMO

We document two cases of viremic and prolonged active infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) where the viral genome was conserved for two months, but infection was with little or no symptoms. The first infection persisted for 80 days and the second for 62 days. Clearance of infection occurred 40 and 41 days, respectively, after development of detectable antibodies. Both cases were identified incidentally in an investigation of reinfection in a cohort of 133,266 laboratory-confirmed infected persons.


Assuntos
Anticorpos Antivirais/sangue , Genoma Viral , RNA Viral/sangue , Viremia/imunologia , Adulto , Doenças Assintomáticas , /virologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Período de Incubação de Doenças Infecciosas , Masculino , Reação em Cadeia da Polimerase Via Transcriptase Reversa , /imunologia , Fatores de Tempo , Viremia/diagnóstico , Viremia/virologia
17.
PLoS Pathog ; 16(12): e1009068, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33382858

RESUMO

Originating from African forests, Zika virus (ZIKV) has now emerged worldwide in urbanized areas, mainly transmitted by Aedes aegypti mosquitoes. Although Aedes albopictus can transmit ZIKV experimentally and was suspected to be a ZIKV vector in Central Africa, the potential of this species to sustain virus transmission was yet to be uncovered until the end of 2019, when several autochthonous transmissions of the virus vectored by Ae. albopictus occurred in France. Aside from these few locally acquired ZIKV infections, most territories colonized by Ae. albopictus have been spared so far. The risk level of ZIKV emergence in these areas remains however an open question. To assess Ae. albopictus' vector potential for ZIKV and identify key virus outbreak predictors, we built a complete framework using the complementary combination of (i) dose-dependent experimental Ae. albopictus exposure to ZIKV followed by time-dependent assessment of infection and systemic infection rates, (ii) modeling of intra-human ZIKV viremia dynamics, and (iii) in silico epidemiological simulations using an Agent-Based Model. The highest risk of transmission occurred during the pre-symptomatic stage of the disease, at the peak of viremia. At this dose, mosquito infection probability was estimated to be 20%, and 21 days were required to reach the median systemic infection rates. Mosquito population origin, either temperate or tropical, had no impact on infection rates or intra-host virus dynamic. Despite these unfavorable characteristics for transmission, Ae. albopictus was still able to trigger and yield large outbreaks in a simulated environment in the presence of sufficiently high mosquito biting rates. Our results reveal a low but existing epidemic potential of Ae. albopictus for ZIKV, that might explain the absence of large scale ZIKV epidemics so far in territories occupied only by Ae. albopictus. They nevertheless support active surveillance and eradication programs in these territories to maintain the risk of emergence to a low level.


Assuntos
Mosquitos Vetores/metabolismo , Mosquitos Vetores/virologia , Infecção por Zika virus/transmissão , Aedes/metabolismo , Aedes/virologia , Animais , Surtos de Doenças , Vetores de Doenças , Epidemias , Humanos , Modelos Teóricos , Saliva/virologia , Carga Viral , Viremia/transmissão , Zika virus/patogenicidade , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/virologia
18.
Viruses ; 12(12)2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33334037

RESUMO

Recent outbreaks of African swine fever virus (ASFV) have seen the movement of this virus into multiple new regions with devastating impact. Many of these outbreaks are occurring in remote, or resource-limited areas, that do not have access to molecular laboratories. Loop-mediated isothermal amplification (LAMP) is a rapid point of care test that can overcome a range of inhibitors. We outline further development of a real-time ASFV LAMP, including field verification during an outbreak in Timor-Leste. To increase field applicability, the extraction step was removed and an internal amplification control (IAC) was implemented. Assay performance was assessed in six different sample matrices and verified for a range of clinical samples. A LAMP detection limit of 400 copies/rxn was determined based on synthetic positive control spikes. A colourmetric LAMP assay was also assessed on serum samples. Comparison of the LAMP assay to a quantitative polymerase chain reaction (qPCR) was performed on clinical ASFV samples, using both serum and oral/rectal swabs, with a substantial level of agreement observed. The further verification of the ASFV LAMP assay, removal of extraction step, implementation of an IAC and the assessment of a range of sample matrix, further support the use of this assay for rapid in-field detection of ASFV.


Assuntos
Vírus da Febre Suína Africana/genética , Febre Suína Africana/epidemiologia , Febre Suína Africana/virologia , Surtos de Doenças , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Febre Suína Africana/diagnóstico , Vírus da Febre Suína Africana/isolamento & purificação , Animais , Feminino , Masculino , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Amplificação de Ácido Nucleico/normas , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Suínos , Viremia
19.
Viruses ; 13(1)2020 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-33375753

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV). We investigated the detailed kinetics of serologic response in patients with SFTS. Twenty-eight patients aged ≥18 years were enrolled between July 2015 and October 2018. SFTS was confirmed by detecting SFTSV RNA in their plasma using reverse transcription polymerase chain reaction. SFTSV-specific IgG and IgM were measured using immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA). We found that SFTSV-specific IgG was detected at days 5-9 after symptom onset, and its titer was rising during the course of disease. SFTSV-specific IgM titer peaked at around week 2-3 from symptom onset. The SFTSV-specific seropositive rates for days 5-9, 10-14, 15-19, and 20-24 from symptom onset using IFA and ELISA were 63%, 76%, 90%, and 100%, and 58%, 86%, 100%, and 100%, respectively, for IgG, whereas they were 32%, 62%, 80%, and 100%, and 53%, 62%, 70%, and 100%, respectively, for IgM. The delayed IgM response could be attributed to the low sensitivity of SFTSV-specific IgM IFA or ELISA and/or impaired immune responses. The IgM test using IFA or ELISA that we used in this study is, therefore, insufficient for the early diagnosis of SFTS.


Assuntos
Phlebovirus/imunologia , /imunologia , Idoso , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Phlebovirus/genética , Doenças Transmitidas por Carrapatos , Viremia
20.
BMC Infect Dis ; 20(1): 815, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33167892

RESUMO

BACKGROUND: The availability of effective, oral direct acting antivirals (DAAs) for hepatitis C virus (HCV) treatment has put elimination of HCV as a public health challenge within reach. However, little is known about the characteristics of transmission networks of people who inject drugs (PWID). METHODS: Sequencing of a segment of the HCV genome was performed on samples collected from a community-based cohort of PWID between August 2005 and December 2016. Phylogenetic trees were inferred, and clusters were identified (70% bootstrap threshold; 0.04 maximum genetic distance threshold). We describe sex, race, age difference, and HIV infection status of potential transmission partners. Logistic regression was used to assess factors associated with being in an HCV cluster. RESULTS: Of 508 HCV genotype 1 viremic PWID, 8% (n = 41) were grouped into 20 clusters, consisting of 19 pairs and 1 triad. In adjusted analyses, female sex (odds ratio [OR] 2.3 [95% confidence interval (CI) 1.2-4.5]) and HIV infection (OR 5.7 [CI 2.7-11.9]) remained independently associated with being in an HCV infection cluster. CONCLUSIONS: Molecular epidemiological analysis reveals that, in this cohort of PWID in Baltimore, HIV infection and female sex were associated with HCV clustering. Combination HCV prevention interventions targeting HIV infected PWID and addressing HCV infection prevention needs of women have potential to advance HCV elimination efforts.


Assuntos
Infecções por HIV/epidemiologia , HIV/genética , Hepacivirus/genética , Hepatite C/epidemiologia , Filogenia , Abuso de Substâncias por Via Intravenosa/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Baltimore/epidemiologia , Análise por Conglomerados , Feminino , Seguimentos , Genótipo , Infecções por HIV/transmissão , Infecções por HIV/virologia , Hepatite C/transmissão , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores Sexuais , Parceiros Sexuais , Viremia/epidemiologia
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