RESUMO
BACKGROUND: Alcohol misuse is an important contributor to sexual acquisition and transmission of HIV in military communities. This cross-sectional study quantified the prevalence of probable problematic alcohol use among male service members in the Armed Forces of the Democratic Republic of the Congo (FARDC), identified associated factors, and investigated associations of alcohol misuse with risky sexual behaviors. METHODS: Participants included 2549 active duty male soldiers ≥ 18 years old. Data were collected via computer-assisted personal-interview from October 2013-April 2014. The Alcohol Use Disorders Identification Test (AUDIT) was used to identify probable problematic alcohol use (AUDIT score ≥ 8) compared to no/low-risk alcohol use (AUDIT score ≤ 7). Bivariate logistic regressions were used to identify factors associated with probable problematic alcohol use. Several multivariable logistic regressions (adjusted for age, marital status, education level) were used to examine associations of probable problematic alcohol use with risky sexual behaviors. Tests were two sided; statistical significance was defined as p < 0.05. RESULTS: Fifteen percent of men screened positive for probable problematic alcohol use. The odds of probable problematic alcohol use were elevated among men who were single and living with a partner (OR = 1.66; 95% CI = 1.24-2.21), ranked as a non-commissioned officer [NCO] (OR = 1.40; 95% CI = 1.10-1.77), and in the 30-39 and 40-49 age groups (OR 30-39 age group = 2.17; 95% CI = 1.56-3.02; OR 40-49 age group = 1.79; 95% CI = 1.26-2.55). Probable problematic alcohol use was associated with increased odds of having sex with a sex worker (SW), having multiple sexual partners, and participating in transactional sex (aOR sex with a SW = 2.36; 95% CI = 1.78-3.13; aOR multiple sexual partners = 2.08; 95% CI = 1.66-2.60; aOR transactional sex = 1.99; 95% CI = 1.59-2.50). CONCLUSIONS: Results emphasize the need to address alcohol use in the FARDC and integrate alcohol abuse education into HIV prevention programs among male service members. Alcohol abuse prevention efforts should target men who are 30-49 years of age, unmarried, and ranked as a NCO. Messages and interventions to reduce alcohol misuse in relation to risky sexual behaviors are needed.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Militares/psicologia , Assunção de Riscos , Comportamento Sexual/psicologia , Adolescente , Adulto , Estudos Transversais , República Democrática do Congo/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Militares/estatística & dados numéricos , Prevalência , Adulto JovemRESUMO
BACKGROUND: Previous research has shown alcohol misuse amplifies the risk of acquiring sexually transmitted infections [STIs], including HIV, by increasing high risk sexual behaviors. Military populations are particularly vulnerable to both alcohol misuse and STIs due to the unique conditions of military service. This study estimated the prevalence of probable hazardous and harmful alcohol use and examined associations with transactional sex, sex with a sex worker, and multiple sexual partners among military personnel in the Armed Forces of the Republic of the Congo (FAC). METHODS: A secondary analysis of data collected from a 2014 seroprevalence and behavioral epidemiology risk survey was performed. Participants included 703 active duty male service members 18 years of age or older who reported ever having sex. Patterns of harmful and hazardous drinking were measured with the Alcohol Use Disorders Identification Test (AUDIT). Participants with an AUDIT score ≥ 8 (indicative of probable hazardous and harmful alcohol use, and possible alcohol dependence) were compared to those with an AUDIT score ≤ 7. RESULTS: A total of 15.8% received a score of 8 or higher on the AUDIT. These participants were more likely to be lower educated and of lower military rank. In separate multivariable models, an AUDIT score ≥ 8 was significantly associated with higher odds of sex with a commercial sex worker and having multiple sexual partners. CONCLUSIONS: Study results emphasize the need to address patterns of harmful and hazardous alcohol use in the FAC and integrate alcohol misuse education into the HIV prevention program. The development of military-specific interventions to reduce alcohol-related risky sexual behaviors are also needed. Lastly, implementing policies such as restricting alcohol availability and sales on military bases, and adding warning labels to advertisements and containers may provide a more comprehensive response to reduce problematic alcohol use.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Militares , Assunção de Riscos , Comportamento Sexual , Adulto , Congo/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Modelos de Riscos Proporcionais , Fatores de Risco , Estudos Soroepidemiológicos , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/etiologia , Infecções Sexualmente Transmissíveis/transmissão , Adulto JovemRESUMO
Substance abuse is a public health priority in the context of the HIV epidemic, especially in military communities. This cross-sectional study quantified alcohol and cannabis use in the Malawi Defence Force and investigated its associations with condom use, transactional sex, multiple sexual partners, and sexual violence. Participants were 944 male and female service members ≥ 18 years old. Data were collected in 2013 using a computer-assisted self-interview. Twenty-four percent of men and women screened positive for hazardous and harmful drinking [Alcohol Use Disorders Identification Test (AUDIT) score ≥ 8]. About 6% reported using cannabis in the past year and 10% reported using cannabis prior to 1 year ago. Multivariable models found elevated adjusted odds of transactional sex and multiple sexual partners for men with an AUDIT score ≥ 8, and men who reported ever using cannabis. The adjusted odds of experiencing sexual violence were also elevated for men who reported ever using cannabis. These findings add to the growing concern that substance use may perpetuate the HIV epidemic in Sub-Saharan Africa by increasing risky sexual behaviors. A comprehensive military HIV prevention response should include substance use education and appropriate care and treatment for individuals screening positive for hazardous and harmful drinking.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Cannabis , Uso da Maconha/epidemiologia , Militares/psicologia , Militares/estatística & dados numéricos , Sexo sem Proteção/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Humanos , Malaui/epidemiologia , Masculino , Assunção de Riscos , Violência/estatística & dados numéricosRESUMO
HIV rapid diagnostic tests (RDTs) combined in an algorithm are the current standard for HIV diagnosis in many sub-Saharan African countries, and extensive laboratory testing has confirmed HIV RDTs have excellent sensitivity and specificity. However, false-positive RDT algorithm results have been reported due to a variety of factors, such as suboptimal quality assurance procedures and inaccurate interpretation of results. We conducted HIV serosurveys in seven sub-Saharan African military populations and recorded the frequency of personnel self-reporting HIV positivity, but subsequently testing HIV-negative during the serosurvey. The frequency of individuals who reported they were HIV-positive but subsequently tested HIV-negative using RDT algorithms ranged from 3.3 to 91.1%, suggesting significant rates of prior false-positive HIV RDT algorithm results, which should be confirmed using biological testing across time in future studies. Simple measures could substantially reduce false-positive results, such as greater adherence to quality assurance guidelines and prevalence-specific HIV testing algorithms as described in the World Health Organization's HIV testing guidelines. Other measures to improve RDT algorithm specificity include classifying individuals with weakly positive test lines as HIV indeterminate and retesting. While expansion of HIV testing in resource-limited countries is critical to identifying HIV-infected individuals for appropriate care and treatment, careful attention to potential causes of false HIV-positive results are needed to prevent the significant medical, psychological, and fiscal costs resulting from individuals receiving a false-positive HIV diagnosis.
Assuntos
Algoritmos , Testes Diagnósticos de Rotina , Infecções por HIV/diagnóstico , Militares , Adolescente , Adulto , África Subsaariana/epidemiologia , Reações Falso-Positivas , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Humanos , Masculino , Programas de Rastreamento/métodos , Guias de Prática Clínica como Assunto , Prevalência , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Autorrelato , Sensibilidade e Especificidade , Organização Mundial da SaúdeRESUMO
BACKGROUND: Continued surveillance of the HIV epidemic is critical to monitor changes in trends and risk behaviors. A 2005 study in the Cameroonian Armed Forces (CAF) found an HIV prevalence of 11.3% among male and female service members. The purpose of the current study is to determine the 5-year change in the HIV prevalence, estimate the prevalence of syphilis, and examine factors associated with infection in the CAF. METHODS: Participants were male and female service members 18 years of age or older who were stationed at one of the 10 military garrisons selected for participation. The military garrisons included in this study were proportionally representative of the CAF by geographic region. Military companies and individuals within the selected garrisons were randomly chosen to participate in the study. Demographic and behavioral risk data were collected from September-November 2011 using personal interviews. Blood was collected for HIV and syphilis testing. RESULTS: Of 2,523 participants tested, 6.0% screened positive for HIV [includes 5.3% who screened positive for HIV only and 0.7% who screened positive for both HIV and syphilis], and 3.1% screened positive for syphilis only. Analyses examining risk factors associated with HIV/syphilis infection (i.e., infected with HIV, infected with syphilis, or co-infected with both HIV and syphilis) were restricted to 2,255 men who reported ever having sex. In a multivariate logistic regression model, the odds of testing positive for HIV/syphilis were higher among men who were separated, divorced, or widowed (adjusted odds ratio [AOR]=3.13, 95% confidence interval [CI]: 1.24-7.89), had sex with sex workers (AOR=1.64, 95% CI: 1.19-2.27), and reported a genital sore/ulcer in the past 12 months preceeding the survey (AOR=1.73, 95% CI: 1.05-2.86). Higher HIV knowledge was protective against HIV/syphilis infection (AOR=0.73, 95% CI: 0.54-0.99). While the overall HIV prevalence in this sample of military personnel was lower than previously reported (6.0% [95% CI: 5.12-6.97] in 2011 vs. 11.3% [95% CI: 10.01-12.68] in 2005; confidence intervals do not overlap), several factors associated with HIV/syphilis infection were identified including being separated, divorced, or widowed, having sex with a sex worker, and reporting a genital sore/ulcer in the past 12 months. CONCLUSION: HIV and syphilis education among all military personnel as they enter service and proceed forward is important to reinforce prevention methods and practices.
Assuntos
Infecções por HIV/epidemiologia , Militares , Sífilis/epidemiologia , Adolescente , Adulto , Camarões/epidemiologia , Estudos Transversais , Testes Diagnósticos de Rotina , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto JovemRESUMO
INTRODUCTION: While sexual and gender-based violence (SGBV) is recognized as an important factor driving the HIV epidemic in sub-Saharan Africa, attitudes toward and prevalence of SGBV within sub-Saharan African military populations are unknown. Data on SGBV were collected from military service members of nine sub-Saharan African militaries. Attitudes related to SGBV and characteristics of those who commit and experience SGBV are reported. METHODS: Data for 8815 service members (8165 men and 650 women) aged 18 years or older who voluntarily participated in the Seroprevalence and Behavioral Epidemiology Risk Surveys from 2009 to 2014 were included in this secondary data analysis. Data were collected on demographics, HIV prevalence, SGBV attitudes, and experiences. Descriptive and bivariate statistical analyses were performed. RESULTS: 5% of men and 9% of women reported experiencing SGBV, and 6% of men reported they had ever committed SGBV. Men and women who had experienced SGBV were significantly more likely to agree with negative gender attitudes toward SGBV, and the majority of those who reported experiencing SGBV reported that SGBV was committed by someone outside of the military. CONCLUSION: This is the first study to examine SGBV in sub-Saharan military populations during periods of limited conflict. It provides evidence that SGBV is experienced by both male and female service members at rates not typically found in previous research examining SGBV in other military populations. A better understanding of SGBV in sub-Saharan military service members is necessary to ensure appropriate services and interventions are part of the military infrastructure.
Assuntos
Violência de Gênero , Infecções por HIV/epidemiologia , Militares , Delitos Sexuais , Adolescente , Adulto , África Subsaariana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Adulto JovemRESUMO
OBJECTIVES: Sexually transmitted infection (STI) prevalence and risk behaviour may differ at different phases of deployment. We examined STI prevalence and sexual behaviour in the predeployment time period (12â months prior) among recently deployed shipboard US Navy and Marine Corps military personnel. METHODS: Data were collected from 1938 male and 515 female service members through an anonymous, self-completed survey assessing sexual behaviours and STI acquisition characteristics in the past 12â months. Cross-sectional sex-stratified descriptive statistics are reported. RESULTS: Overall, 67% (n=1262/1896) reported last sex with a military beneficiary (spouse, n=931, non-spouse service member, n=331). Among those with a sexual partner outside their primary partnership, 24% (n=90/373) reported using a condom the last time they had sex and 30% (n=72/243) reported their outside partner was a service member. In total, 90% (n=210/233) reported acquiring their most recent STI in the USA (88%, n=126/143 among those reporting ≥1 deployments and an STI ≥1â year ago) and a significantly higher proportion (p<0.01) of women than men acquired the STI from their regular partner (54% vs 21%) and/or a service member (50% vs 26%). CONCLUSIONS: Findings suggest a complex sexual network among service members and military beneficiaries. Findings may extend to other mobile civilian and military populations. Data suggest most STI transmission within the shipboard community may occur in local versus foreign ports but analyses from later time points in deployment are needed. These data may inform more effective STI prevention interventions.
Assuntos
Preservativos/estatística & dados numéricos , Militares/psicologia , Militares/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Parceiros Sexuais/psicologia , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Adulto , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Prevalência , Assunção de Riscos , Comportamento Sexual/psicologia , Infecções Sexualmente Transmissíveis/transmissão , Estados Unidos/epidemiologiaRESUMO
Free condoms provided by the government are often not used by Botswana Defence Force (BDF) personnel due to a perceived unpleasant scent and unattractive wrapper. Formative work with the BDF found that scented condoms and military-inspired (camouflage) wrapper graphics were appealing to personnel. A non-randomized intervention study was implemented to determine whether condom wrapper graphics and scent improved condom use in the BDF. Four military sites were selected for participation. Two sites in the south received the intervention condom wrapped in a generic wrapper and two sites in the north received the intervention condom wrapped in a military-inspired wrapper; intervention condoms were either scented or unscented. Two hundred and eleven male soldiers who ever had sex, aged 18-30 years, and stationed at one of the selected sites consented to participate. Sexual activity and condom use were measured pre- and post-intervention using sexual behavior diaries. A condom use rate (CUR; frequency of protected sex divided by the total frequency of sex) was computed for each participant. Mean CURs significantly increased over time (85.7% baseline vs. 94.5% post-intervention). Adjusted odds of condom use over time were higher among participants who received the intervention condom packaged in the military wrapper compared with the generic wrapper. Adjusted odds of condom use were also higher for participants who reported using scented vs. unscented condoms. Providing scented condoms and condoms packaged in a military-inspired wrapper may help increase condom use and reduce HIV infection among military personnel.
Assuntos
Preservativos/estatística & dados numéricos , Comportamento Contraceptivo/estatística & dados numéricos , Militares/estatística & dados numéricos , Odorantes , Rotulagem de Produtos/métodos , Rotulagem de Produtos/estatística & dados numéricos , Adolescente , Adulto , Botsuana , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Sexo Seguro/estatística & dados numéricos , Marketing Social , Adulto JovemRESUMO
This study compares self-reported sexual behaviors from a retrospective survey and a prospective diary among Botswana Defence Force (BDF) personnel. One hundred sixty-one male participants, aged 18-30, completed two weekly prospective diaries and a retrospective survey querying them about behaviors reported during the same time frame as the diaries. Most reported behaviors were similar between the two data collection methods. However, there was low agreement for reporting sex with a spouse and exchanging material goods for sex with a casual partner; frequency of sex and condom use rates (CURs) among married participants also differed. When comparing survey condom use frequencies to diary CURs, the level of agreement diminished from the always to occasionally condom use categories. Inconsistencies in reporting may be due to the frequency of the sexual behavior, question sensitivity, the data collection setting, and the interpretation of response categories. Further research is needed to improve accurate reporting of sexual behaviors.
Assuntos
Preservativos/estatística & dados numéricos , Coleta de Dados/métodos , Militares/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Adulto , Botsuana , Inquéritos Epidemiológicos , Humanos , Masculino , Rememoração Mental , Militares/psicologia , Estudos Prospectivos , Estudos Retrospectivos , Autorrelato , Comportamento Sexual/psicologia , Parceiros Sexuais , Fatores Socioeconômicos , Revelação da VerdadeRESUMO
Preventing HIV infection is a priority for militaries. HIV prevention research is needed to monitor existing programme, identify areas for modification, and develop new interventions. Correct and consistent condom use is highly effective against HIV. However, use among soldiers is lower than ideal. This study describes condom use behaviours and examines correlates of use in the Botswana Defence Force (BDF). Analyses were based on 211 male BDF personnel, aged 18-30, who completed a cross-sectional survey that collected baseline data for an intervention study. Results showed that 51% of participants reported always using condoms, 35% used condoms most times, and 14% used condoms occasionally/never. Condom use varied by partner type and was typically higher with casual partners in comparison to regular partners. After adjustment for age and marital status, factors associated with lower condom use included excessive alcohol use, perception that using condoms reduce sexual pleasure, and having a trusted partner. However, higher levels of HIV knowledge and reports of being circumcised were protective against lower condom use. HIV interventions aimed at increasing condom use in the BDF should address condom perceptions, alcohol abuse, and issues of trust. Innovative ways to increase condom use in this population should also be explored.
Assuntos
Preservativos/estatística & dados numéricos , Infecções por HIV/prevenção & controle , Militares , Comportamento Sexual/estatística & dados numéricos , Parceiros Sexuais/psicologia , Adulto , Botsuana , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Modelos Logísticos , Masculino , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Overwhelming evidence, including three clinical trials, shows that male circumcision (MC) reduces the risk of HIV infection among men. However, data from recent Lesotho Demographic and Health Surveys do not demonstrate MC to be protective against HIV. These contradictory findings could partially be due to inaccurate self-reported MC status used to estimate MC prevalence. This study describes MC characteristics among men applying for Lesotho Defence Force recruitment and seeks to assess MC self-reported accuracy through comparison with physical-examination-based data. METHODS AND FINDINGS: During Lesotho Defence Force applicant screening in 2009, 241 (77%) of 312 men, aged 18-25 y, consented to a self-administered demographic and MC characteristic survey and physician-performed genital examination. The extent of foreskin removal was graded on a scale of 1 (no evidence of MC) to 4 (complete MC). MC was self-reported by 27% (nâ=â64/239) of participants. Of the 64 men self-reporting being circumcised, physical exam showed that 23% had no evidence of circumcision, 27% had partial circumcision, and 50% had complete circumcision. Of the MCs reportedly performed by a medical provider, 3% were Grade 1 and 73% were Grade 4. Of the MCs reportedly performed by traditional circumcisers, 41% were Grade 1, while 28% were Grade 4. Among participants self-reporting being circumcised, the odds of MC status misclassification were seven times higher among those reportedly circumcised by initiation school personnel (odds ratioâ=â7.22; 95% CIâ=â2.29-22.75). CONCLUSIONS: Approximately 27% of participants self-reported being circumcised. However, only 50% of these men had complete MC as determined by a physical exam. Given this low MC self-report accuracy, countries scaling up voluntary medical MC (VMMC) should obtain physical-exam-based MC data to guide service delivery and cost estimates. HIV prevention messages promoting VMMC should provide comprehensive education regarding the definition of VMMC.
Assuntos
Circuncisão Masculina/estatística & dados numéricos , Exame Físico/estatística & dados numéricos , Autorrelato , Adulto , Estudos Transversais , Demografia , Pesquisas sobre Atenção à Saúde , Humanos , Lesoto/epidemiologia , Masculino , Adulto JovemRESUMO
Convenient and well-performing protein detection methods for a wide range of targets are in great demand for biomedical research and future diagnostics. Assays without the need for washing steps while still unaffected when analyzing complex biological samples are difficult to develop. Herein, we report a well-characterized nucleic acid proximity-based assay using antibodies, called Proximity Extension Assay (PEA), showing good performance in plasma samples. Target-specific antibody pairs are linked to DNA strands that upon simultaneous binding to the target analyte create a real-time PCR amplicon in a proximity-dependent manner enabled by the action of a DNA polymerase. 3'Exonuclease-capable polymerases were found to be clearly superior in sensitivity over non-3'exonuclease ones. A PEA was set up for IL-8 and GDNF in a user-friendly, homogenous assay displaying femtomolar detection sensitivity, good recovery in human plasma, high specificity and up to 5-log dynamic range in 1 µL samples. Furthermore, we have illustrated the use of a macro-molecular crowding matrix in combination with this homogeneous assay to drive target binding for low-affinity antibodies, thereby improving the sensitivity and increasing affinity reagent availability by lowering assay development dependency on high-affinity antibodies. Assay performance was also confirmed for a multiplex version of PEA.
Assuntos
Proteínas Sanguíneas/análise , Imunoensaio/métodos , Anticorpos , Proteínas Sanguíneas/imunologia , Exonucleases , Humanos , Sondas de Oligonucleotídeos , Reação em Cadeia da Polimerase , Água/químicaRESUMO
A high throughput protein biomarker discovery tool has been developed based on multiplexed proximity ligation assays in a homogeneous format in the sense of no washing steps. The platform consists of four 24-plex panels profiling 74 putative biomarkers with sub-pm sensitivity each consuming only 1 µl of human plasma sample. The system uses either matched monoclonal antibody pairs or the more readily available single batches of affinity purified polyclonal antibodies to generate the target specific reagents by covalently linking with unique nucleic acid sequences. These paired sequences are united by DNA ligation upon simultaneous target binding forming a PCR amplicon. Multiplex proximity ligation assays thereby converts multiple target analytes into real-time PCR amplicons that are individually quantified using microfluidic high capacity qPCR in nano liter volumes. The assay shows excellent specificity, even in multiplex, by its dual recognition feature, its proximity requirement, and most importantly by using unique sequence specific reporter fragments on both antibody-based probes. To illustrate the potential of this protein detection technology, a pilot biomarker research project was performed using biobanked plasma samples for the detection of colorectal cancer using a multivariate signature.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Glicosídicos Associados a Tumores/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Análise Multivariada , Inibidor Secretado de Peptidases Leucocitárias/sangue , Estatísticas não Paramétricas , Inibidor Tecidual de Metaloproteinase-1/sangue , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
The herpesvirus entry mediator (HVEM), a member of the TNF receptor (TNFR) superfamily, can act as a molecular switch that modulates T cell activation by propagating positive signals from the TNF-related ligand LIGHT (TNFR superfamily 14), or inhibitory signals through the Ig superfamily member B and T lymphocyte attenuator (BTLA). Competitive binding analysis and mutagenesis reveals a unique BTLA binding site centered on a critical lysine residue in cysteine-rich domain 1 of HVEM. The BTLA binding site on HVEM overlaps with the binding site for the herpes simplex virus 1 envelope glycoprotein D, but is distinct from where LIGHT binds, yet glycoprotein D inhibits the binding of both ligands, potentially nullifying the pathway. The binding site on HVEM for BTLA is conserved in the orphan TNFR, UL144, present in human CMV. UL144 binds BTLA, but not LIGHT, and inhibits T cell proliferation, selectively mimicking the inhibitory cosignaling function of HVEM. The demonstration that distinct herpesviruses target the HVEM-BTLA cosignaling pathway suggests the importance of this pathway in regulating T cell activation during host defenses.
Assuntos
Herpesviridae/imunologia , Ativação Linfocitária/imunologia , Receptores Imunológicos/metabolismo , Receptores do Fator de Necrose Tumoral/fisiologia , Receptores Virais/fisiologia , Linfócitos T/virologia , Sequência de Bases , Sítios de Ligação , Ligação Competitiva , Citomegalovirus/imunologia , Citomegalovirus/fisiologia , Herpesviridae/fisiologia , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 1/fisiologia , Humanos , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Dados de Sequência Molecular , Filogenia , Receptores do Fator de Necrose Tumoral/imunologia , Receptores do Fator de Necrose Tumoral/metabolismo , Membro 14 de Receptores do Fator de Necrose Tumoral , Receptores Virais/imunologia , Receptores Virais/metabolismo , Transdução de Sinais , Linfócitos T/imunologia , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Fator de Necrose Tumoral alfa/metabolismo , Proteínas do Envelope Viral/metabolismo , Proteínas Virais/metabolismoRESUMO
Lymphotoxin-beta receptor (LTbetaR) and CD40 are members of the tumor necrosis factor family of signaling receptors that regulate cell survival or death through activation of NF-kappaB. These receptors transmit signals through downstream adaptor proteins called tumor necrosis factor receptor-associated factors (TRAFs). In this study, the crystal structure of a region of the cytoplasmic domain of LTbetaR bound to TRAF3 has revealed an unexpected new recognition motif, 388IPEEGD393, for TRAF3 binding. Although this motif is distinct in sequence and structure from the PVQET motif in CD40 and PIQCT in the regulator TRAF-associated NF-kappaB activator (TANK), recognition is mediated in the same binding crevice on the surface of TRAF3. The results reveal structurally adaptive "hot spots" in the TRAF3-binding crevice that promote molecular interactions driving specific signaling after contact with LTbetaR, CD40, or the downstream regulator TANK.