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1.
J Infect Dis ; 228(4): 487-499, 2023 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-37207618

RESUMEN

BACKGROUND: Women's increased risk of HIV acquisition during pregnancy and postpartum may be mediated by changes in vaginal microbiota and/or cytokines. METHODS: A cohort of 80 Kenyan women who were HIV-1 seronegative contributed 409 vaginal samples at 6 pregnancy time points: periconception, positive pregnancy test result, first trimester, second trimester, third trimester, and postpartum. Concentrations of vaginal bacteria linked with HIV risk and Lactobacillus spp were measured using quantitative polymerase chain reaction. Cytokines were measured by immunoassay. RESULTS: Based on Tobit regression, later pregnancy time points were associated with lower concentrations of Sneathia spp (P = .01), Eggerthella sp type 1 (P = .002), and Parvimonas sp type 2 (P = .02) and higher concentrations of Lactobacillus iners (P < .001), Lactobacillus crispatus (P < .001), Lactobacillus vaginalis (P < .001), interleukin 6 (P < .001), TNF (P = .004), C-X-C motif chemokine ligand 10 (CXCL10; P < .001), C-C motif ligand 3 (P = .009), C-C motif ligand 4 (P < .001), C-C motif ligand 5 (P = .002), interleukin 1ß (P = .02), and interleukin 8 (P = .002). Most cervicovaginal cytokines and vaginal bacteria clustered separately in principal component analysis, except for CXCL10, which did not group with either cytokines or bacteria. The shift toward a Lactobacillus-dominated microbiota during pregnancy mediated the relationship between pregnancy time point and CXCL10. CONCLUSIONS: Increases in proinflammatory cytokines, but not vaginal bacterial taxa linked with higher HIV risk, could provide an explanation for increased HIV susceptibility during pregnancy and postpartum.


Asunto(s)
Infecciones por VIH , Mediadores de Inflamación , Embarazo , Femenino , Humanos , Kenia/epidemiología , Ligandos , Vagina/microbiología , Bacterias , Periodo Posparto , Citocinas , Infecciones por VIH/complicaciones , ARN Ribosómico 16S/genética
2.
J Infect Dis ; 228(3): 343-352, 2023 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-36823694

RESUMEN

BACKGROUND: The purpose of this study was to assess if single nucleotide polymorphisms (SNPs) in lung mucins MUC5B and MUC5AC are associated with Mycobacterium tuberculosis outcomes. METHODS: Independent SNPs in MUC5B and MUC5AC (genotyped by Illumina HumanOmniExpress array) were assessed for associations with tumor necrosis factor (TNF) concentrations (measured by immunoassay) in cerebral spinal fluid (CSF) from tuberculous meningitis (TBM) patients. SNPs associated with CSF TNF concentrations were carried forward for analyses of pulmonary and meningeal tuberculosis susceptibility and TBM mortality. RESULTS: MUC5AC SNP rs28737416 T allele was associated with lower CSF concentrations of TNF (P = 1.8 × 10-8) and IFN-γ (P = 2.3 × 10-6). In an additive genetic model, rs28737416 T/T genotype was associated with higher susceptibility to TBM (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.03-1.49; P = .02), but not pulmonary tuberculosis (OR, 1.11, 95% CI, .98-1.25; P = .10). TBM mortality was higher among participants with the rs28737416 T/T and T/C genotypes (35/119, 30.4%) versus the C/C genotype (11/89, 12.4%; log-rank P = .005) in a Vietnam discovery cohort (n = 210), an independent Vietnam validation cohort (n = 87; 9/87, 19.1% vs 1/20, 2.5%; log-rank P = .02), and an Indonesia validation cohort (n = 468, 127/287, 44.3% vs 65/181, 35.9%; log-rank P = .06). CONCLUSIONS: MUC5AC variants may contribute to immune changes that influence TBM outcomes.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Meníngea , Humanos , Tuberculosis Meníngea/genética , Tuberculosis Meníngea/complicaciones , Citocinas/genética , Genotipo , Factor de Necrosis Tumoral alfa/genética , Polimorfismo de Nucleótido Simple , Mucina 5AC/genética
3.
Sex Transm Infect ; 96(1): 3-9, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31197065

RESUMEN

OBJECTIVES: Recent studies have identified vaginal bacterial taxa associated with increased HIV risk. A possible mechanism to explain these results is that individual taxa differentially promote cervicovaginal inflammation. This study aimed to explore relationships between concentrations of bacteria previously linked to HIV acquisition and vaginal concentrations of proinflammatory cytokines and chemokines. METHODS: In this cross-sectional analysis, concentrations of 17 bacterial taxa and four proinflammatory cytokines (interleukin (IL)-1ß, IL-6, IL-10 and tumour necrosis factor alpha (TNFα)) and two proinflammatory chemokines (IL-8 and interferon gamma-induced protein 10) were measured in vaginal swabs collected from 80 HIV-uninfected women. Cytokine and chemokine concentrations were compared between women with bacterial concentrations above or below the lower limit of detection as determined by quantitative PCR for each taxon. Principal component analysis was used to create a summary score for closely correlated bacteria, and linear regression analysis was used to evaluate associations between this score and increasing concentrations of TNFα and IL-1ß. RESULTS: Detection of Dialister micraerophilus (p=0.01), Eggerthella sp type 1 (p=0.05) or Mycoplasma hominis (p=0.03) was associated with higher TNFα concentrations, and detection of D. micraerophilus (p<0.01), Eggerthella sp type 1 (p=0.04), M. hominis (p=0.02) or Parvimonas sp type 2 (p=0.05) was associated with significantly higher IL-1ß concentrations. Seven bacterial taxa (D. micraerophilus, Eggerthella sp type 1, Gemella asaccharolytica, Sneathia sp, Megasphaera sp, M. hominis and Parvimonas sp type 2) were found to be highly correlated by principal component analysis (eigenvalue 5.24, explaining 74.92% of variability). Linear regression analysis demonstrated associations between this principal component and concentrations of TNFα (ß=0.55, 95% CI 0.01 to 1.08; p=0.048) and IL-1ß (ß=0.96, 95% CI 0.19 to 1.74; p=0.016). CONCLUSIONS: This study provides evidence that several highly correlated vaginal bacterial taxa may influence vaginal cytokine and chemokine concentrations. These results suggest a mechanism where the presence of specific bacterial taxa could influence HIV susceptibility by increasing vaginal inflammation.


Asunto(s)
Bacterias/aislamiento & purificación , Quimiocinas/análisis , Citocinas/análisis , Infecciones por VIH/diagnóstico , Vagina/microbiología , Adolescente , Adulto , Bacterias/clasificación , Bacterias/genética , Quimiocinas/inmunología , Estudios Transversales , Citocinas/inmunología , Susceptibilidad a Enfermedades/diagnóstico , Susceptibilidad a Enfermedades/inmunología , Susceptibilidad a Enfermedades/virología , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/fisiología , Humanos , Interleucina-1beta/análisis , Interleucina-1beta/inmunología , Microbiota , Persona de Mediana Edad , Factores de Riesgo , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/inmunología , Vagina/química , Vagina/inmunología , Adulto Joven
4.
Int J Gynecol Cancer ; 24(5): 950-5, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24819658

RESUMEN

OBJECTIVES: The objectives of this study are to identify the characteristics of febrile gynecologic oncology patients and to evaluate the utility of common diagnostic procedures used to assess the etiologies of their fevers. METHODS/MATERIALS: Retrospective data were collected for 200 consecutive patients admitted to the gynecologic oncology service at 1 institution between January 2008 and December 2012 for a diagnosis of fever. Data were collected using contingency tables, and the χ test was used as appropriate. RESULTS: Of the patients admitted for evaluation of fever, 142 (71%) of 200 had a documented fever during hospitalization. The most common etiologies of fever in this population were urinary tract infections (28%) and bloodstream infections (27%), whereas 24% of those admitted for fever did not have a source identified. Abdominal/pelvic computed tomography (CT) scans established the etiology of fever in 53 (60%) of the 89 patients tested, whereas chest x-ray and chest CT were diagnostic for 6% and 21%, respectively. Blood and urine cultures were diagnostic in 29% and 32% of cases, respectively. Patients admitted within 30 days of surgery had a higher percentage of wound infections (38% vs 10%, P < 0.001) as compared with those admitted for more than 30 days after surgery. CONCLUSIONS: The initial evaluation of the febrile gynecologic oncology patient without obvious source by history and examination should include urinalysis with reflex culture and blood cultures. Abdominopelvic and chest CT may be useful when fever persists and initial assessment is unrevealing. Chest x-ray is commonly done but infrequently diagnostic. Wound exploration may be important in patients with fevers for more than 30 days after surgery.


Asunto(s)
Terapia Combinada/efectos adversos , Fiebre/diagnóstico , Fiebre/etiología , Neoplasias de los Genitales Femeninos/complicaciones , Adulto , Anciano , Femenino , Estudios de Seguimiento , Neoplasias de los Genitales Femeninos/terapia , Hospitalización , Humanos , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
5.
bioRxiv ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-39005354

RESUMEN

Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome that is prevalent in reproductive-age women worldwide. Adverse outcomes associated with BV include an increased risk of sexually acquired Human Immunodeficiency Virus (HIV), yet the immunological mechanisms underlying this association are not well understood. To investigate BV driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and peripheral blood mononuclear cells (PBMC). Immunofluorescence analysis of genital mucosal tissues revealed a reduced density of CD3 + CD4 + CCR5 + cells in the VT lamina propria of individuals with compared to those without BV (median 243.8 cells/mm 2 BV-vs 106.9 cells/mm 2 BV+, p=0.043). High-parameter flow cytometry of VT biopsies revealed an increased frequency in individuals with compared to those without BV of dysfunctional CD39 + conventional CD4 + T cells (Tconv) (median frequency 15% BV-vs 30% BV+, p adj =0.0331) and tissue-resident CD69 + CD103 + Tconv (median frequency 24% BV-vs 38% BV+, p adj =0.0061), previously reported to be implicated in HIV acquisition and replication. Our data suggests that BV elicits diverse and complex VT T cell alterations and expands on potential immunological mechanisms that may promote adverse outcomes including HIV susceptibility.

6.
Int J STD AIDS ; 34(8): 557-566, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36945124

RESUMEN

BACKGROUND: The association between vaginal washing and HIV risk may be mediated by vaginal washing-associated changes in vaginal microbiota. METHODS: Data from a cohort of HIV-negative US and Kenyan women enrolled in the Preventing Vaginal Infections trial were analyzed. Vaginal fluid samples and vaginal washing data were collected every 2 months for 12 months. Bacterial relative abundances were measured by broad-range 16S rRNA gene polymerase chain reaction with next generation sequencing. Generalized estimating equations were used to evaluate the association between vaginal washing and i) the Shannon Diversity Index (SDI); and ii) mean change in percent bacterial relative abundances, with application of a 10% false discovery rate (FDR). RESULTS: Participants (N = 111) contributed 93/630 (14.8%) vaginal washing visits. Mean SDI was 0.74 points higher (95% CI 0.35, 1.14; p < 0.001) at washing visits among US participants (N = 26). Vaginal washing was not associated with SDI in Kenyan participants (N = 85). There were no associations between vaginal washing and vaginal bacterial relative abundances after applying the FDR. CONCLUSIONS: The discordant results in Kenyan versus US women suggests the link between vaginal washing and sub-optimal vaginal microbiota may be context specific. Vaginal microbial shifts may not fully explain the association between vaginal washing and HIV acquisition.


Asunto(s)
Infecciones por VIH , Microbiota , Femenino , Humanos , Estudios de Cohortes , Kenia/epidemiología , ARN Ribosómico 16S/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Vagina/microbiología , Bacterias/genética , Microbiota/genética , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control
7.
J Virol ; 85(14): 7005-19, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21543495

RESUMEN

The E2 glycoprotein of hepatitis C virus (HCV) mediates viral attachment and entry into target hepatocytes and elicits neutralizing antibodies in infected patients. To characterize the structural and functional basis of HCV neutralization, we generated a novel panel of 78 monoclonal antibodies (MAbs) against E2 proteins from genotype 1a and 2a HCV strains. Using high-throughput focus-forming reduction or luciferase-based neutralization assays with chimeric infectious HCV containing structural proteins from both genotypes, we defined eight MAbs that significantly inhibited infection of the homologous HCV strain in cell culture. Two of these bound E2 proteins from strains representative of HCV genotypes 1 to 6, and one of these MAbs, H77.39, neutralized infection of strains from five of these genotypes. The three most potent neutralizing MAbs in our panel, H77.16, H77.39, and J6.36, inhibited infection at an early postattachment step. Receptor binding studies demonstrated that H77.39 inhibited binding of soluble E2 protein to both CD81 and SR-B1, J6.36 blocked attachment to SR-B1 and modestly reduced binding to CD81, and H77.16 blocked attachment to SR-B1 only. Using yeast surface display, we localized epitopes for the neutralizing MAbs on the E2 protein. Two of the strongly inhibitory MAbs, H77.16 and J6.36, showed markedly reduced binding when amino acids within hypervariable region 1 (HVR1) and at sites ∼100 to 200 residues away were changed, suggesting binding to a discontinuous epitope. Collectively, these studies help to define the structural and functional complexity of antibodies against HCV E2 protein with neutralizing potential.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Epítopos/metabolismo , Hepacivirus/inmunología , Proteínas del Envoltorio Viral/inmunología , Animales , Secuencia de Bases , Células CHO , Línea Celular , Cricetinae , Cricetulus , Cartilla de ADN , Hepacivirus/genética , Humanos , Unión Proteica , Proteínas del Envoltorio Viral/metabolismo
8.
AIDS ; 34(12): 1725-1733, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32701583

RESUMEN

OBJECTIVE: To evaluate the relationship between cervical cytokine/chemokine concentrations and HIV-1 acquisition in peripartum Kenyan women. DESIGN: Nested case-control study. METHODS: Women participating in a prospective study of peripartum HIV acquisition in Kenya (the Mama Salama Study), were tested for HIV-1 at 1-3 month intervals during pregnancy and through 9 months postpartum. Cases positive for HIV-1 RNA during follow-up (N = 14), were matched 3 : 1 with HIV-negative controls (N = 42) based on age, marital status, partner HIV-1 status, transactional sex, and timing of cervical swab collection. Concentrations of five cytokines (IL-1ß, IL-6, IL-10, IFNγ, and TNFα) and four chemokines (IL-8, C-X-C motif chemokine ligand 10 (CXCL10), macrophage inflammatory protein-1 α, and macrophage inflammatory protein-1 ß) were measured from cervical swabs collected at the visit prior to HIV-1 diagnosis (cases) or matched gestational/postpartum time (controls). Cytokine/chemokine concentrations were compared between cases and controls using Wilcoxon rank-sum tests. Principal component analysis was used to create a summary score for closely correlated cytokines/chemokines. Associations with HIV-1 acquisition were analyzed using conditional logistic regression. Path analysis was used to evaluate hypothesized relationships between CXCL10, vaginal washing, Nugent score, and HIV-1 acquisition. RESULTS: Conditional logistic regression analysis demonstrated an association between increased concentrations of CXCL10 and HIV-1 acquisition (odds ratio = 1.74, 95% confidence interval 1.04, 2.93; P = 0.034). Path analysis confirmed a positive independent association between higher concentrations of CXCL10 and HIV-1 acquisition (path coefficient = 0.37, 95% confidence interval 0.15, 0.59; P < 0.001). CONCLUSION: HIV-1 acquisition was associated with increased cervical concentrations of CXCL10 in pregnant and postpartum women.


Asunto(s)
Quimiocina CXCL10/metabolismo , Infecciones por VIH , VIH-1 , Estudios de Casos y Controles , Femenino , Humanos , Kenia , Ligandos , Periodo Posparto , Embarazo , Estudios Prospectivos
9.
Dev Genes Evol ; 219(11-12): 609-12, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20091319

RESUMEN

In order to identify prospective limb muscle cells in a frog, we cloned Lbx1 from the direct developing frog Eleutherodactylus coqui. Like in embryos of the frog Xenopus laevis but unlike in other vertebrates, EcLbx1 is expressed in all trunk somites. Like in embryos of chick, mouse, and zebrafish, cells expressing EcLbx1 are then found in limb buds, consistent with migration of those cells from somites. EcLbx1 is also expressed in the dorsal spinal cord as in other vertebrates.


Asunto(s)
Anuros/embriología , Extremidades/embriología , Regulación del Desarrollo de la Expresión Génica/fisiología , Proteínas de Homeodominio/metabolismo , Somitos/metabolismo , Secuencia de Aminoácidos , Animales , Anuros/anatomía & histología , Clonación Molecular , Cartilla de ADN/genética , Embrión no Mamífero/anatomía & histología , Extremidades/anatomía & histología , Hawaii , Proteínas de Homeodominio/genética , Hibridación in Situ , Datos de Secuencia Molecular , Filogenia , Puerto Rico , Médula Espinal/metabolismo
10.
Open Forum Infect Dis ; 6(11): ofz449, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31723573

RESUMEN

Patients with chronic granulomatous disease are at increased risk for invasive aspergillosis. Cryptic Aspergillus species are being increasingly recognized as distinct causes of infection in this population. In this study, we describe the first case of Aspergillus udagawae vertebral osteomyelitis in a patient with X-linked chronic granulomatous disease.

11.
AIDS ; 33(7): 1225-1230, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-31048629

RESUMEN

OBJECTIVES: A recent study of HIV serodiscordant couples found that depot medroxyprogesterone acetate (DMPA) and oral contraceptive pills (OCPs) were associated with increased HIV risk in the presence, but not in the absence, of bacterial vaginosis. We assessed whether bacterial vaginosis is an effect modifier of the association between hormonal contraception and HIV seroconversion in female sex workers (FSWs) in Mombasa, Kenya. DESIGN: Prospective cohort study. METHODS: Data collected from HIV-negative FSWs from 1993 to 2017 were analyzed. Cox proportional hazards models were used to assess the relationship between HIV seroconversion and use of DMPA, OCPs, or hormonal contraceptive implants (Norplant, Jadelle). RESULTS: A total of 1985 women contributed 7127 person-years of follow-up; 307 women seroconverted to HIV (4.32/100 person-years). DMPA was significantly associated with elevated risk of HIV seroconversion in women with [aHR 1.56, 95% confidence interval (CI) 1.08-2.25; P = 0.02] and without (aHR 2.08, 95% CI 1.46-2.97; P < 0.001) bacterial vaginosis (interaction P = 0.4). Similarly, OCP use was associated with increased HIV risk both in the presence (aHR 1.50, 95% CI 0.94-2.39; P = 0.09) and absence (aHR 1.61, 95% CI 0.99-2.64; P = 0.06) of bacterial vaginosis (interaction P = 0.9), though neither stratum reached statistical significance. Implants were not associated with HIV seroconversion overall (aHR 0.99, 95% CI 0.40-2.45; P = 0.9), or in women with (aHR 0.65, 95% CI 0.16-2.72; P = 0.6) and without (aHR 1.39, 95% CI 0.43-4.46; P = 0.6) bacterial vaginosis (interaction P = 0.5). CONCLUSION: Bacterial vaginosis had no effect on the associations between hormonal contraceptives and HIV seroconversion in this cohort. Contraceptive implants were not associated with increased HIV risk compared with no contraception.


Asunto(s)
Anticonceptivos Hormonales Orales/efectos adversos , Seropositividad para VIH/epidemiología , Acetato de Medroxiprogesterona/efectos adversos , Trabajadores Sexuales/estadística & datos numéricos , Vaginosis Bacteriana/epidemiología , Adulto , Anticoncepción/métodos , Anticonceptivos Hormonales Orales/administración & dosificación , Femenino , Seropositividad para VIH/transmisión , Humanos , Kenia/epidemiología , Acetato de Medroxiprogesterona/administración & dosificación , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Adulto Joven
12.
PLoS One ; 14(1): e0210825, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30677048

RESUMEN

Vaginal washing is a common practice associated with adverse outcomes including bacterial vaginosis (BV) and HIV infection. Prior studies have not examined the associations between vaginal washing and individual vaginal bacteria, or whether these associations are independent of the effect of vaginal washing on BV. The purpose of this study was to characterize the association between vaginal washing and the presence and concentrations of vaginal bacteria associated with optimal and sub-optimal vaginal states. The analysis utilized data from participants in the placebo arm of the Preventing Vaginal Infections trial, which enrolled HIV-uninfected women from the United States and Kenya. Detection of bacterial taxa associated with BV was compared between visits with versus without reported vaginal washing. The effect of vaginal washing on a number of vaginal bacteria differed substantially (p<0.05) between the US and Kenya, so results were stratified by country. In US women, vaginal washing was associated with a significantly higher likelihood of detection of BV associated bacterium 1 (BVAB1) (relative risk [RR] 1.55, 95% confidence interval [CI] 1.15-2.09, p = 0.004), BVAB2 (RR 1.99, 95%CI 1.46-2.71, p<0.001), Mageeibacillus indolicus (RR 2.08, 95%CI 1.46-2.96, p<0.001), Atopobium vaginae (RR 1.34, 95%CI 1.13-1.59, p = 0.001), Leptotrichia/Sneathia species (RR 1.66, 95% CI 1.33-2.09, p<0.001), Megasphaera species (RR 1.78, 95%CI 1.34-2.37, p<0.001) and Gardnerella vaginalis (RR 1.08, 95%CI 1.01-1.16, p = 0.02). No significant association between vaginal washing and bacterial detection was found in Kenyan women. Adjustment for bacterial vaginosis diagnosed by Gram stain did not alter these results. This study provides evidence that the association between vaginal washing and detection of individual bacterial taxa can vary regionally. For some vaginal bacteria, the association with vaginal washing may be independent of the effect on Gram stain detection of BV. Larger prospective studies in diverse geographic settings should explore whether eliminating vaginal washing impacts the presence and concentrations of key vaginal bacteria.


Asunto(s)
Ducha Vaginal/efectos adversos , Vaginosis Bacteriana/etiología , Adolescente , Adulto , Carga Bacteriana , Comparación Transcultural , Femenino , Humanos , Kenia , Microbiota , Persona de Mediana Edad , Riesgo , Especificidad de la Especie , Estados Unidos , Vagina/microbiología , Ducha Vaginal/métodos , Vaginosis Bacteriana/microbiología , Adulto Joven
13.
Open Forum Infect Dis ; 5(1): ofx272, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29399597

RESUMEN

Infection with Helicobacter cinaedi can encompass a wide spectrum of clinical manifestations, including fever, rash, endocarditis, osteomyelitis, and meningitis. The present case demonstrates the ability of H cinaedi to masquerade as acute rheumatic fever and represents the first reported case of cardiac tamponade caused by H cinaedi.

14.
Virology ; 422(2): 174-84, 2012 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-22078164

RESUMEN

A recent study with flaviviruses suggested that structural dynamics of the virion impact antibody neutralization via exposure of ostensibly cryptic epitopes. To determine whether this holds true for the distantly related hepatitis C virus (HCV), whose neutralizing epitopes may be obscured by a glycan shield, apolipoprotein interactions, and the hypervariable region on the E2 envelope protein, we assessed how time and temperature of pre-incubation altered monoclonal antibody (MAb) neutralization of HCV. Notably, several MAbs showed increased inhibitory activity when pre-binding was performed at 37°C or after longer pre-incubation periods, and a corresponding loss-of-neutralization was observed when pre-binding was performed at 4°C. A similar profile of changes was observed with acute and chronic phase sera from HCV-infected patients. Our data suggest that time and temperature of incubation modulate epitope exposure on the conformational ensembles of HCV virions and thus, alter the potency of antibody neutralization.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Epítopos/inmunología , Hepacivirus/inmunología , Anticuerpos contra la Hepatitis C/inmunología , Sitios de Unión de Anticuerpos , Línea Celular , Epítopos/genética , Hepacivirus/genética , Hepacivirus/metabolismo , Hepatitis C/sangre , Humanos , Cinética , Temperatura , Factores de Tiempo
15.
Evodevo ; 2: 20, 2011 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-21978790

RESUMEN

BACKGROUND: RNAs for embryo patterning and for germ cell specification are localized to the vegetal cortex of the oocyte of Xenopus laevis. In oocytes of the direct developing frog Eleutherodactylus coqui, orthologous RNAs for patterning are not localized, raising the question as to whether RNAs and other components of germ plasm are localized in this species. METHODS: To identify germ plasm, E. coqui embryos were stained with DiOC6(3) or examined by in situ hybridization for dazl and DEADSouth RNAs. The cDNAs for the E. coqui orthologues were cloned by RT-PCR using degenerate primers. To examine activity of the E. coqui orthologues, RNAs, made from constructs of their 3'UTRs with mCherry, were injected into X. laevis embryos. RESULTS: Both DiOC6(3) and dazl and DEADSouth in situs identified many small islands at the vegetal surface of cleaving E. coqui embryos, indicative of germ plasm. Dazl was also expressed in primordial germ cells in the genital ridge. The 3'UTRs of E. coqui dazl and DEADSouth directed primordial germ cell specific protein synthesis in X. laevis. CONCLUSIONS: E. coqui utilizes germ plasm with RNAs localized to the vegetal cortex to specify primordial germ cells. The large number of germ plasm islands suggests that an increase in the amount of germ plasm was important in the evolution of the large E. coqui egg.

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