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1.
Nature ; 546(7658): 411-415, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28538734

RESUMO

Although the recent Zika virus (ZIKV) epidemic in the Americas and its link to birth defects have attracted a great deal of attention, much remains unknown about ZIKV disease epidemiology and ZIKV evolution, in part owing to a lack of genomic data. Here we address this gap in knowledge by using multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analysed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental United States. We find that ZIKV circulated undetected in multiple regions for many months before the first locally transmitted cases were confirmed, highlighting the importance of surveillance of viral infections. We identify mutations with possible functional implications for ZIKV biology and pathogenesis, as well as those that might be relevant to the effectiveness of diagnostic tests.


Assuntos
Filogenia , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia , Zika virus/genética , Zika virus/isolamento & purificação , Animais , Brasil/epidemiologia , Colômbia/epidemiologia , Culicidae/virologia , Surtos de Doenças/estatística & dados numéricos , Genoma Viral/genética , Mapeamento Geográfico , Honduras/epidemiologia , Humanos , Metagenoma/genética , Epidemiologia Molecular , Mosquitos Vetores/virologia , Mutação , Vigilância em Saúde Pública , Porto Rico/epidemiologia , Estados Unidos/epidemiologia , Zika virus/classificação , Zika virus/patogenicidade , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia
2.
Emerg Infect Dis ; 28(2): 473-475, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35076369

RESUMO

To determine the extent of exposure to Zika virus (ZIKV) and chikungunya virus (CHIKV) in Jamaica, we collected serum from 584 pregnant women during 2017-2019. We found that 15.6% had antibodies against ZIKV and 83.6% against CHIKV. These results indicate potential recirculation of ZIKV but not CHIKV in the near future.


Assuntos
Febre de Chikungunya , Vírus Chikungunya , Dengue , Infecção por Zika virus , Zika virus , Febre de Chikungunya/epidemiologia , Feminino , Humanos , Jamaica/epidemiologia , Gravidez , Estudos Soroepidemiológicos , Infecção por Zika virus/epidemiologia
3.
J Antimicrob Chemother ; 77(1): 218-222, 2021 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-34557895

RESUMO

OBJECTIVES: To quantitatively determine the antimicrobial susceptibility of clinical Neisseria gonorrhoeae isolates from men with urethral discharge in Jamaica and to describe the syndromic treatment therapies administered. METHODS: Urethral eSwabs (Copan) were collected from 175 men presenting with urethral discharge to the Comprehensive Health Centre STI Clinic, Kingston, Jamaica. Clinical information was collected and MICs of eight antimicrobials were determined for N. gonorrhoeae isolates (n = 96) using Etest and interpreted using CLSI criteria. RESULTS: The median age of the subjects was 28 years (range: 18-73 years) with a median of 2 sexual partners (range: 1-25) per male in the previous 3 months. All examined N. gonorrhoeae isolates were susceptible to ceftriaxone (96/96), azithromycin (91/91), cefixime (91/91) and spectinomycin (91/91). For ciprofloxacin and gentamicin, respectively, 98.9% (91/92) and 91.3% (84/92) of the isolates were susceptible and 1.1% (1/92) and 8.7% (8/92) showed intermediate susceptibility/resistance. For tetracycline and benzylpenicillin, respectively, 38.0% (35/92) and 22.0% (20/91) of the isolates were susceptible, 52.2% (48/92) and 74.7% (68/91) showed intermediate susceptibility/resistance and 9.8% (9/92) and 3.3% (3/91) were resistant. Syndromic treatment was administered as follows: 93.1% received 250 mg of ceftriaxone intramuscularly plus 100 mg of doxycycline orally q12h for 1-2 weeks and 6.9% received 500 mg of ciprofloxacin orally plus 100 mg of doxycycline orally q12h for 1 week. CONCLUSIONS: Ceftriaxone (250 mg) remains appropriate for gonorrhoea treatment in the examined population of men in Kingston, Jamaica. Surveillance of N. gonorrhoeae AMR should be expanded in Jamaica and other Caribbean countries to guide evidence-based treatment guidelines.


Assuntos
Gonorreia , Neisseria gonorrhoeae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Criança , Pré-Escolar , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Humanos , Lactente , Jamaica/epidemiologia , Masculino , Testes de Sensibilidade Microbiana
4.
Curr HIV/AIDS Rep ; 17(2): 125-137, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32140979

RESUMO

PURPOSE OF REVIEW: An increasing body of evidence indicates that persons living with HIV (PLWH) display dysfunctional immunometabolism. Here, we provide an updated review of this topic and its relationship to HIV-associated immune stimuli and age-related disease. RECENT FINDINGS: HIV infection alters immunometabolism by increasing reliance on aerobic glycolysis for energy and productive infection and repurposing oxidative phosphorylation machinery for immune cell proliferation and survival. Recent studies in PLWH with diabetes mellitus or cardiovascular disease have identified an association with elevated T cell and monocyte glucose metabolism, respectively. Immunometabolic dysfunction has also been observed in PLWH in frailty and additional studies suggest a role for immunometabolism in non-AIDS defining cancers and neurocognitive disease. There is a plethora of HIV-associated immune stimuli that could drive immunometabolic dysfunction and age-related disease in PLWH, but studies directly examining their relationship are lacking. Immunometabolic dysfunction is characteristic of HIV infection and is a potential link between HIV-associated stimuli and age-related comorbidities.


Assuntos
Infecções por HIV/imunologia , Infecções por HIV/patologia , Monócitos/metabolismo , Linfócitos T/metabolismo , Doenças Cardiovasculares/imunologia , Comorbidade , Diabetes Mellitus/imunologia , Glicólise/fisiologia , Infecções por HIV/complicações , Humanos , Inflamação/patologia , Monócitos/imunologia , Neoplasias/imunologia , Fosforilação Oxidativa , Linfócitos T/imunologia
5.
PLoS Pathog ; 12(10): e1005891, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27736984

RESUMO

Chikungunya virus (CHIKV) is a re-emerging global pathogen with pandemic potential, which causes fever, rash and debilitating arthralgia. Older adults over 65 years are particularly susceptible to severe and chronic CHIKV disease (CHIKVD), accounting for >90% of all CHIKV-related deaths. There are currently no approved vaccines or antiviral treatments available to limit chronic CHIKVD. Here we show that in old mice excessive, dysregulated TGFß production during acute infection leads to a reduced immune response and subsequent chronic disease. Humans suffering from CHIKV infection also exhibited high TGFß levels and a pronounced age-related defect in neutralizing anti-CHIKV antibody production. In vivo reduction of TGFß levels minimized acute joint swelling, restored neutralizing antibody production and diminished chronic joint pathology in old mice. This study identifies increased and dysregulated TGFß secretion as one key mechanism contributing to the age-related loss of protective anti-CHIKV-immunity leading to chronic CHIKVD.


Assuntos
Envelhecimento/imunologia , Febre de Chikungunya/imunologia , Fator de Crescimento Transformador beta/imunologia , Adulto , Idoso , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vírus Chikungunya , Modelos Animais de Doenças , Suscetibilidade a Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase , Fator de Crescimento Transformador beta/biossíntese
6.
J Immunol ; 196(11): 4437-44, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27207806

RESUMO

Immune cells cycle between a resting and an activated state. Their metabolism is tightly linked to their activation status and, consequently, functions. Ag recognition induces T lymphocyte activation and proliferation and acquisition of effector functions that require and depend on cellular metabolic reprogramming. Likewise, recognition of pathogen-associated molecular patterns by monocytes and macrophages induces changes in cellular metabolism. As obligate intracellular parasites, viruses manipulate the metabolism of infected cells to meet their structural and functional requirements. For example, HIV-induced changes in immune cell metabolism and redox state are associated with CD4(+) T cell depletion, immune activation, and inflammation. In this review, we highlight how HIV modifies immunometabolism with potential implications for cure research and pathogenesis of comorbidities observed in HIV-infected patients, including those with virologic suppression. In addition, we highlight recently described key methods that can be applied to study the metabolic dysregulation of immune cells in disease states.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , HIV/imunologia , HIV/patogenicidade , HIV/metabolismo , Infecções por HIV/virologia , Humanos , Inflamação/imunologia , Inflamação/metabolismo
8.
J Vasc Res ; 54(4): 195-199, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28618422

RESUMO

OBJECTIVE: Fluid-phase pinocytosis is a receptor-independent mechanism of endocytosis that occurs in all mammalian cells and may be a mechanism for the uptake of LDL by macrophages. As there are currently no methods for the measurement of fluid-phase pinocytosis by individual aortic cells in vivo, we sought to identify a suitable method. METHODS: ApoE-/- mice were retro-orbitally injected with AngioSPARK fluorescent nanoparticles specifically designed to not interact with cells. After 24 h, mice were sacrificed, and the aortas were isolated and then digested to analyze aortic cell uptake of AngioSPARK by flow cytometry. RESULTS: CD11b-expressing aortic macrophages from mice injected with AngioSPARK showed high levels of fluid-phase pinocytosis compared to aortic cells not expressing CD11b (4,393.7 vs. 408.3 mean fluorescence intensity [MFI], respectively). CONCLUSION: This new technique allows for the measurement of fluid-phase pinocytosis by aortic cells in vivo, making it possible to examine the cell-signaling molecules and drugs that affect this process. Published by S. Karger AG, Basel.


Assuntos
Aorta/metabolismo , Doenças da Aorta/metabolismo , Aterosclerose/metabolismo , Citometria de Fluxo/métodos , Macrófagos/metabolismo , Pinocitose , Animais , Aorta/patologia , Doenças da Aorta/genética , Doenças da Aorta/patologia , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/genética , Aterosclerose/patologia , Antígeno CD11b/metabolismo , Modelos Animais de Doenças , Corantes Fluorescentes/metabolismo , Predisposição Genética para Doença , Masculino , Camundongos Knockout , Fenótipo
9.
J Immunol ; 193(11): 5595-603, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25367121

RESUMO

Monocyte activation during HIV-1 infection is associated with increased plasma levels of inflammatory markers and increased risk for premature development of age-related diseases. Because activated monocytes primarily use glucose to support cellular metabolism, we hypothesized that chronic monocyte activation during HIV-1 infection induces a hypermetabolic response with increased glucose uptake. To test this hypothesis, we evaluated glucose transporter 1 (Glut1) expression and glucose uptake by monocyte subpopulations in HIV-seropositive (HIV(+)) treatment-naive individuals (n = 17), HIV(+) individuals on combination antiretroviral therapy with viral loads below detection (n = 11), and HIV-seronegative (HIV(-)) individuals (n = 16). Surface expression of Glut1 and cellular uptake of the fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose were analyzed by flow cytometry on monocyte subpopulations. Irrespective of treatment status, monocytes from HIV(+) persons had significantly increased surface expression of Glut1 compared with those from HIV(-) controls. Nonclassical (CD14(+)CD16(++)) and intermediate (CD14(++)CD16(+)) monocyte subpopulations showed higher Glut1 expression than did classical (CD14(++)CD16(-)) monocytes. Intermediate monocytes from treatment-naive HIV(+) individuals also showed increased uptake of 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose compared with those from HIV(-) controls. Our results show that HIV infection is associated with increased glucose metabolism in monocytes and that Glut1 expression by proinflammatory monocytes is a potential marker of inflammation in HIV-infected subjects. However, the possibility exists whereby other Gluts such as Glut3 and Glut4 may also support the influx of glucose into activated and inflammatory monocyte populations.


Assuntos
Transportador de Glucose Tipo 1/metabolismo , Glucose/metabolismo , Infecções por HIV/imunologia , HIV/imunologia , Monócitos/imunologia , Adulto , Idoso , Antirretrovirais/administração & dosagem , Antirretrovirais/efeitos adversos , Austrália , Biomarcadores/metabolismo , Combinação de Medicamentos , Feminino , Glucose/análogos & derivados , Transportador de Glucose Tipo 1/genética , Infecções por HIV/terapia , Soropositividade para HIV , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/virologia , Regulação para Cima
10.
J Lipid Res ; 55(1): 115-27, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24212237

RESUMO

Previous studies have demonstrated that the ATP-binding cassette transporters (ABC)A1 and ABCG1 function in many aspects of cholesterol efflux from macrophages. In this current study, we continued our investigation of extracellular cholesterol microdomains that form during enrichment of macrophages with cholesterol. Human monocyte-derived macrophages and mouse bone marrow-derived macrophages, differentiated with macrophage colony-stimulating factor (M-CSF) or granulocyte macrophage colony-stimulation factor (GM-CSF), were incubated with acetylated LDL (AcLDL) to allow for cholesterol enrichment and processing. We utilized an anti-cholesterol microdomain monoclonal antibody to reveal pools of unesterified cholesterol, which were found both in the extracellular matrix and associated with the cell surface, that we show function in reverse cholesterol transport. Coincubation of AcLDL with 50 µg/ml apoA-I eliminated all extracellular and cell surface-associated cholesterol microdomains, while coincubation with the same concentration of HDL only removed extracellular matrix-associated cholesterol microdomains. Only at an HDL concentration of 200 µg/ml did HDL eliminate the cholesterol microdomains that were cell-surface associated. The deposition of cholesterol microdomains was inhibited by probucol, but it was increased by the liver X receptor (LXR) agonist TO901317, which upregulates ABCA1 and ABCG1. Extracellular cholesterol microdomains did not develop when ABCG1-deficient mouse bone marrow-derived macrophages were enriched with cholesterol. Our findings show that generation of extracellular cholesterol microdomains is mediated by ABCG1 and that reverse cholesterol transport occurs not only at the cell surface but also within the extracellular space.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Colesterol/metabolismo , Microdomínios da Membrana/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Animais , Anticolesterolemiantes/farmacologia , Apolipoproteína A-I/metabolismo , Células Cultivadas , Humanos , Hidrocarbonetos Fluorados/farmacologia , Metabolismo dos Lipídeos , Lipoproteínas HDL/metabolismo , Receptores X do Fígado , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Nucleares Órfãos/agonistas , Receptores Nucleares Órfãos/metabolismo , Probucol/farmacologia , Sulfonamidas/farmacologia
11.
Viruses ; 15(4)2023 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-37112824

RESUMO

The Caribbean enjoys a long-standing eminence as a popular tourist destination; however, over the years it has also amassed the sobriquet "arbovirus hotspot". As the planet warms and vectors expand their habitats, a cognizant working knowledge of the lesser-known arboviruses and the factors that influence their emergence and resurgence becomes essential. The extant literature on Caribbean arboviruses is spread across decades of published literature and is quite often difficult to access, and, in some cases, is obsolete. Here, we look at the lesser-known arboviruses of the insular Caribbean and examine some of the drivers for their emergence and resurgence. We searched the scientific literature databases PubMed and Google Scholar for peer-reviewed literature as well as scholarly reports. We included articles and reports that describe works resulting in serological evidence of the presence of arboviruses and/or arbovirus isolations in the insular Caribbean. Studies without serological evidence and/or arbovirus isolations as well as those including dengue, chikungunya, Zika, and yellow fever were excluded. Of the 545 articles identified, 122 met the inclusion criteria. A total of 42 arboviruses were identified in the literature. These arboviruses and the drivers that affect their emergence/resurgence are discussed.


Assuntos
Infecções por Arbovirus , Arbovírus , Febre de Chikungunya , Dengue , Febre Amarela , Infecção por Zika virus , Zika virus , Humanos , Região do Caribe , Dengue/epidemiologia
12.
Am J Trop Med Hyg ; 109(6): 1344-1350, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-37871588

RESUMO

Mother to child transmission (MTCT) of human T-cell lymphotropic virus (HTLV)-1 is associated with increased risk of adult T-cell leukemia and can be unrecognized without routine antenatal screening. We assessed the seroprevalence of HTLV-1/2 among pregnant women attending The University Hospital of the West Indies Antenatal Clinic, 2019, and validated a cost-effective strategy to screen antenatal clinic attendees for HTLV-1/2. Residual antenatal samples from 370 women were tested for HTLV-1/2 by chemiluminescence microparticle immunoassay (CMIA). Six samples were confirmed HTLV-1 positive by Western blot (none for HTLV-2) for a prevalence of 1.62%. Four mother-child pairs were able to be recruited for HTLV testing of children, with two children testing HTLV-1/2 positive. Medical records of HTLV-1-infected women revealed that all women breastfed, indicating an unrecognized risk for HTLV MTCT. To assess whether pooling of samples as a cost-reduction strategy could be introduced, we pooled all antenatal samples received between November and December 2021 into 12 pools of eight samples/pool. Two pools were CMIA positive, and de-pooling of samples identified two CMIA-positive samples (one per pool), both confirmed as HTLV-1 by Western blot. These results indicate that HTLV-1 remains prevalent in pregnant Jamaican women and that sample pooling can be a cost-effective strategy to limit MTCT in Jamaica.


Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Adulto , Feminino , Humanos , Gravidez , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/prevenção & controle , Estudos Soroepidemiológicos , Jamaica/epidemiologia , Transmissão Vertical de Doenças Infecciosas , Diagnóstico Pré-Natal , Linfócitos T
13.
J Lipid Res ; 53(1): 34-42, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22058424

RESUMO

Accumulation of cholesterol by macrophage uptake of LDL is a key event in the formation of atherosclerotic plaques. Previous research has shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) is present in atherosclerotic plaques and promotes aortic lipid accumulation. However, it has not been determined whether murine GM-CSF-differentiated macrophages take up LDL to become foam cells. GM-CSF-differentiated macrophages from LDL receptor-null mice were incubated with LDL, resulting in massive macrophage cholesterol accumulation. Incubation of LDL receptor-null or wild-type macrophages with increasing concentrations of ¹²5I-LDL showed nonsaturable macrophage LDL uptake that was linearly related to the amount of LDL added, indicating that LDL uptake was mediated by fluid-phase pinocytosis. Previous studies suggest that phosphoinositide 3-kinases (PI3K) mediate macrophage fluid-phase pinocytosis, although the isoform mediating this process has not been determined. Because PI3Kγ is known to promote aortic lipid accumulation, we investigated its role in mediating macrophage fluid-phase pinocytosis of LDL. Wild-type macrophages incubated with LDL and the PI3Kγ inhibitor AS605240 or PI3Kγ-null macrophages incubated with LDL showed an ∼50% reduction in LDL uptake and cholesterol accumulation compared with wild-type macrophages incubated with LDL only. These results show that GM-CSF-differentiated murine macrophages become foam cells by fluid-phase pinocytosis of LDL and identify PI3Kγ as contributing to this process.


Assuntos
LDL-Colesterol/metabolismo , Classe Ib de Fosfatidilinositol 3-Quinase/fisiologia , Células Espumosas/fisiologia , Macrófagos/efeitos dos fármacos , Pinocitose/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Células Espumosas/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Lipoproteínas LDL , Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinoxalinas/farmacologia , Tiazolidinedionas/farmacologia
14.
Am J Trop Med Hyg ; 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35320778

RESUMO

The Caribbean region is lacking an assessment of the antibody response and side effects experienced after AstraZeneca COVID-19 vaccination (AZD1222). We examined severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) IgG levels and report the side effects noted in a Jamaican population after AZD1222 vaccination. Median RBD IgG levels for persons without evidence of previous SARS-CoV-2 infection were 43.1 binding international units (bIU)/mL 3 to 7 weeks after the first dose, increasing to 100.1 bIU/mL 3 to 7 weeks after the second dose, and decreasing to 46.9 bIU/mL 16 to 22 weeks after the second dose. The median RBD IgG level 2 to 8 weeks after symptom onset for unvaccinated SARS-CoV-2-infected persons of all disease severities was 411.6 bIU/mL. Common AZD1222 side effects after the first dose were injection site pain, headache, and chills. Most people reported no side effects after the second dose. AZD1222 is widely used across the English-speaking Caribbean, and our study provides evidence for its continued safe and effective use in vaccination programs.

15.
J Clin Virol Plus ; 2(4): 100124, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36415687

RESUMO

A cross-sectional SARS-CoV-2 serosurvey was conducted after the Omicron surge in Jamaica using 1,540 samples collected during March - May 2022 from persons attending antenatal, STI and non-communicable diseases clinics in Kingston, Jamaica. SARS-CoV-2 spike receptor binding domain (RBD) and/or nucleocapsid IgG antibodies were detected for 88.4% of the study population, with 77.0% showing evidence of previous SARS-CoV-2 infection. Of persons previously infected with SARS-CoV-2 and/or with COVID-19 vaccination, 9.6% were negative for spike RBD IgG, most of which were unvaccinated previously infected persons. Amongst unvaccinated previously infected people, age was associated with testing spike RBD IgG negative. When considering all samples, median spike RBD IgG levels were 131.6 BAU/mL for unvaccinated persons with serological evidence of past infection, 90.3 BAU/mL for vaccinated persons without serological evidence of past infection, and 896.1 BAU/mL for vaccinated persons with serological evidence of past infection. Our study of the first reported SARS-CoV-2 serosurvey in Jamaica shows extensive SARS-CoV-2 population immunity, identifies a substantial portion of the population lacking spike RBD IgG, and provides additional evidence for increasing COVID-19 vaccine coverage in Jamaica.

16.
medRxiv ; 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36172133

RESUMO

A cross-sectional SARS-CoV-2 serosurvey was conducted after the Omicron surge in Jamaica using 1,540 samples collected during March â€" May 2022 from persons attending antenatal, STI and non-communicable diseases clinics in Kingston, Jamaica. SARS-CoV-2 spike receptor binding domain (RBD) and/or nucleocapsid IgG antibodies were detected for 88.4% of the study population, with 77.0% showing evidence of previous SARS-CoV-2 infection. Of persons previously infected with SARS-CoV-2 and/or with COVID-19 vaccination, 9.6% were negative for spike RBD IgG, most of which were unvaccinated previously infected persons. Amongst unvaccinated previously infected people, age was associated with testing spike RBD IgG negative. When considering all samples, median spike RBD IgG levels were 131.6 BAU/mL for unvaccinated persons with serological evidence of past infection, 90.3 BAU/mL for vaccinated persons without serological evidence of past infection, and 896.1 BAU/mL for vaccinated persons with serological evidence of past infection. Our study of the first reported SARS-CoV-2 serosurvey in Jamaica shows extensive SARS-CoV-2 population immunity, identifies a substantial portion of the population lacking spike RBD IgG, and provides additional evidence for increasing COVID-19 vaccine coverage in Jamaica.

17.
AIDS ; 36(10): 1327-1336, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35727147

RESUMO

OBJECTIVE: Immune dysfunction and chronic inflammation are characteristic of HIV infection and diabetes mellitus, with CD4 + T-cell metabolism implicated in the pathogenesis of each disease. However, there is limited information on CD4 + T-cell metabolism in HIV+ persons with diabetes mellitus. We examined CD4 + T-cell glucose metabolism in HIV+ women with and without diabetes mellitus. DESIGN: A case-control study was used to compare CD4 + T-cell glucose metabolism in women with HIV with or without diabetes mellitus. METHODS: Nondiabetic (HIV+DM-, N = 20) or type 2 diabetic HIV+ women with (HIV+DM+, N  = 16) or without (HIV+DMTx+, N  = 18) antidiabetic treatment were identified from the WIHS and matched for age, race/ethnicity, smoking status and CD4 + cell count. CD4 + T-cell immunometabolism was examined by flow cytometry, microfluidic qRT-PCR of metabolic genes, and Seahorse extracellular flux analysis of stimulated CD4 + T cells. RESULTS: HIV+DM+ displayed a significantly elevated proportion of CD4 + T cells expressing the immunometabolic marker GLUT1 compared with HIV+DMTx+ and HIV+DM- ( P  = 0.04 and P  = 0.01, respectively). Relative expression of genes encoding key enzymes for glucose metabolism pathways were elevated in CD4 + T cells of HIV+DM+ compared with HIV+DMTx+ and HIV+DM-. T-cell receptor (TCR)-activated CD4 + T cells from HIV+DM+ showed elevated glycolysis and oxidative phosphorylation compared with HIV+DM-. CONCLUSION: CD4 + T cells from HIV+DM+ have elevated glucose metabolism. Treatment of diabetes mellitus among women with HIV may partially correct CD4 + T-cell metabolic dysfunction.


Assuntos
Diabetes Mellitus , Infecções por HIV , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Feminino , Glucose/metabolismo , Humanos
18.
BMC Biotechnol ; 11: 13, 2011 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-21281514

RESUMO

BACKGROUND: Monocyte-derived macrophages contribute to atherosclerotic plaque formation. Therefore, manipulating macrophage function could have significant therapeutic value. The objective of this study was to determine transduction efficiency of two HIV-based lentiviral vector configurations as delivery systems for the transduction of primary human blood monocyte-derived macrophages. RESULTS: Human blood monocytes were transduced using two VSV-G pseudotyped HIV-1 based lentiviral vectors containing EGFP expression driven by either native HIV-LTR (VRX494) or EF1α promoters (VRX1090). Lentiviral vectors were added to cultured macrophages at different times and multiplicities of infection (MOI). Transduction efficiency was assessed using fluorescence microscopy and flow cytometry. Macrophages transduced between 2 and 120 hours after culturing showed the highest transduction efficiency at 2-hours transduction time. Subsequently, cells were transduced 2 hours after culturing at various vector concentrations (MOIs of 5, 10, 25 and 50) to determine the amount of lentiviral vector particles required to maximally transduce human monocyte-derived macrophages. On day 7, all transduced cultures showed EGFP-positive cells by microscopy. Flow cytometric analysis showed with all MOIs a peak shift corresponding to the presence of EGFP-positive cells. For VRX494, transduction efficiency was maximal at an MOI of 25 to 50 and ranged between 58 and 67%. For VRX1090, transduction efficiency was maximal at an MOI of 10 and ranged between 80 and 90%. Thus, transductions performed with VRX1090 showed a higher number of EGFP-positive cells than VRX494. CONCLUSIONS: This report shows that VSV-G pseudotyped HIV-based lentiviral vectors can efficiently transduce human blood monocyte-derived macrophages early during differentiation using low particle numbers that do not interfere with differentiation of monocytes into macrophages.


Assuntos
Vetores Genéticos/genética , HIV-1/genética , Fator Estimulador de Colônias de Macrófagos/farmacologia , Macrófagos/metabolismo , Transdução Genética/métodos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Células Cultivadas , Citometria de Fluxo , Engenharia Genética/métodos , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Humanos , Fator Estimulador de Colônias de Macrófagos/metabolismo , Glicoproteínas de Membrana/genética , Proteínas do Envelope Viral/genética
19.
Arterioscler Thromb Vasc Biol ; 30(10): 2022-31, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20634472

RESUMO

OBJECTIVE: To examine the pinocytotic pathways mediating native low-density lipoprotein (LDL) uptake by human macrophage colony-stimulating factor-differentiated macrophages (the predominant macrophage phenotype in human atherosclerotic plaques). METHODS AND RESULTS: We identified the kinase inhibitor SU6656 and the Rho GTPase inhibitor toxin B as inhibitors of macrophage fluid-phase pinocytosis of LDL. Assessment of macropinocytosis by time-lapse microscopy revealed that both drugs almost completely inhibited macropinocytosis, although LDL uptake and cholesterol accumulation by macrophages were only partially inhibited (approximately 40%) by these agents. Therefore, we investigated the role of micropinocytosis in mediating LDL uptake in macrophages and identified bafilomycin A1 as an additional partial inhibitor (approximately 40%) of macrophage LDL uptake that targeted micropinocytosis. When macrophages were incubated with both bafilomycin A1 and SU6656, inhibition of LDL uptake was additive (reaching 80%), showing that these inhibitors target different pathways. Microscopic analysis of fluid-phase uptake pathways in these macrophages confirmed that LDL uptake occurs through both macropinocytosis and micropinocytosis. CONCLUSIONS: Our findings show that human macrophage colony-stimulating factor-differentiated macrophages take up native LDL by macropinocytosis and micropinocytosis, underscoring the importance of both pathways in mediating LDL uptake by these cells.


Assuntos
Lipoproteínas LDL/metabolismo , Fator Estimulador de Colônias de Macrófagos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Pinocitose/fisiologia , Transporte Biológico Ativo/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Indóis/farmacologia , Macrolídeos/farmacologia , Macrófagos/citologia , Microscopia Imunoeletrônica , Pinocitose/efeitos dos fármacos , Sulfonamidas/farmacologia
20.
Int J Infect Dis ; 105: 333-336, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33610776

RESUMO

BACKGROUND: The performance of the Roche Elecsys® Anti-SARS-CoV-2, Abbott Architect SARS-CoV-2 IgM, Abbott Architect SARS-CoV-2 IgG, Euroimmun SARS-CoV-2 IgA, Euroimmun SARS-CoV-2 IgG ELISA, and Trillium IgG/IgM rapid assays was evaluated in Jamaica. METHODS: Diagnostic sensitivities of the assays were assessed by testing serum samples from SARS-CoV-2 PCR-confirmed persons and diagnostic specificity was assessed by testing serum samples collected during 2018-2019 from healthy persons and from persons with antibodies to a wide range of viral infections. RESULTS: Serum samples collected ≥14 days after onset of symptoms, or an initial SARS-CoV-2 RT-PCR positive test for asymptomatics, showed diagnostic sensitivities ranging from 67.9 to 75.0% when including all possible disease severities and increased to 90.0-95.0% when examining those with moderate to critical disease. Grouping moderate to critical disease showed a significant association with a SARS-CoV-2 antibody positive result for all assays. Diagnostic specificity ranged from 96.7 to 100.0%. For all assays examined, SARS-CoV-2 real-time PCR cycle threshold (Ct) values of the initial nasopharyngeal swab sample testing positive were significantly different for samples testing antibody positive versus negative. CONCLUSIONS: These data from a predominantly African descent Caribbean population show comparable diagnostic sensitivities and specificities for all testing platforms assessed and limited utility of these tests for persons with asymptomatic and mild infections.


Assuntos
Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2/imunologia , COVID-19/sangue , COVID-19/imunologia , Região do Caribe , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Jamaica , SARS-CoV-2/isolamento & purificação , Sensibilidade e Especificidade
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