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Pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission, but uptake and adherence among young men who have sex with men (YMSM) remains suboptimal. New PrEP formulations may enhance PrEP use, but little is known about their acceptability. We enrolled 39 cis- and transgender YMSM (age 18-34) from Boston, MA; Jackson, MS; Birmingham, AL; and New Orleans, LA, who participated in video-based focus groups (n = 30) or in-depth interviews (n = 9) to examine how new PrEP products (e.g., injections, monthly pills, implants) are perceived and might be improved for YMSM. Focus groups were transcribed, coded, and analyzed using grounded theory and content analysis. Nearly half (46%) of participants were Black; 11% identified as Hispanic. Seventy-nine percent were PrEP experienced. Product preference was driven by the desire for flexible, safe, effective, and affordable PrEP options. A majority of participants preferred subcutaneous injections every 6 months or monthly pills dispersed in 3 or 4 doses. Subcutaneous injections and batched monthly pills were favored by those with demanding schedules and those who desired fewer provider visits; monthly pills were more appealing for those who feared needles. Despite broad preferences for longer-acting products for convenience, participants raised concerns regarding side effects and waning protection after missed doses. Participants felt that more education about safety and efficacy profiles of new products could influence their attitudes. These findings suggest that it is important to prioritize YMSM's dynamic lifestyles during product development, and that product safety and efficacy information should be accessible in youth-friendly language.
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Recent studies have shown social determinants of health (SDOH) to impact HIV care engagement. This cross-sectional study (Oct 20-Apr 21) assessed the impact of a range of SDOH on HIV care engagement using data from HIV Care Connect, a consortium of three HIV care facility-led programs (Alabama, Florida, Mississippi). The exposures were captured using the PRAPARE (Protocol for Responding to and Assessing Patient Assets, Risks, and Experiences) scale. The outcome was captured using the Index of Engagement in HIV Care scale. Participants (n = 132) were predominantly non-White (87%) and male (52%) with a median age of 41 years. Multivariable logistic regression adjusted for various sociodemographics showed lower HIV care engagement to be associated with being uninsured/publicly insured, having 1-3 unmet needs, socially integrating ≤five times/week, and having stable housing. Factors such as unmet needs, un-/underinsurance, and social integration may be addressed by healthcare and community organizations.
Assessing How Social Drivers of Health Affect Engagement in HIV Care in the Southern United StatesIt has been found that social factors that have a direct impact on health affect engagement in HIV Care among people living with HIV. We included various social drivers of health to see how they affect engagement in HIV Care. We used data between October 2020 and April 2021 from a project titled HIV Care Connect, which is a group of three facilities providing HIV care in Alabama, Florida, and Mississippi. We used social drivers of health as risk factors from a scale called PRAPARE (Protocol for Responding to and Assessing Patient Assets, Risks, and Experiences). Engagement in HIV care was measured by using a scale called Index of Engagement in HIV Care. A total of 132 participants were included. Majority of the participants were of races other than white (87%), male (52%) and were aged 41 years on average. Statistical analysis showed that participants without insurance or with public insurance, participants with 1-3 unsatisfied needs, participants that met with other people less than or equal to five times a week, and participants that had reliable housing had lower engagement in HIV care. These factors have a potential to be addressed by healthcare and community organizations.
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Infecções por HIV , Determinantes Sociais da Saúde , Humanos , Estudos Transversais , Masculino , Infecções por HIV/psicologia , Infecções por HIV/epidemiologia , Adulto , Determinantes Sociais da Saúde/estatística & dados numéricos , Feminino , Pessoa de Meia-Idade , Sudeste dos Estados Unidos/epidemiologia , Adulto Jovem , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricosRESUMO
Batborne henipaviruses, such as Nipah virus and Hendra virus, represent a major threat to global health due to their propensity for spillover, severe pathogenicity, and high mortality rate in human hosts. Coupled with the absence of approved vaccines or therapeutics, work with the prototypical species and uncharacterized, emergent species is restricted to high biocontainment facilities. There is a scarcity of such specialized spaces for research, and often the scope and capacity of research which can be conducted at BSL-4 is limited. Therefore, there is a pressing need for innovative life-cycle modeling systems to enable comprehensive research within lower biocontainment settings. This work showcases tetracistronic, transcription and replication competent minigenomes for Nipah virus, Hendra virus, Cedar virus, and Ghana virus, which encode viral proteins facilitating budding, fusion, and receptor binding. We validate the functionality of all encoded viral proteins and demonstrate a variety of applications to interrogate the viral life cycle. Notably, we found that the Cedar virus replicase exhibits remarkable promiscuity, efficiently rescuing minigenomes from all tested henipaviruses. We also apply this technology to GhV, an emergent species which has so far not been isolated in culture. We demonstrate that the reported sequence of GhV is incomplete, but that this missing sequence can be substituted with analogous sequences from other henipaviruses. Use of our GhV system establishes the functionality of the GhV replicase and identifies two antivirals which are highly efficacious against the GhV polymerase.
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In vivo imaging system (IVIS) is a powerful tool for the study of infectious diseases, providing the ability to non-invasively follow viral infection in an individual animal over time. Recombinant henipaviruses expressing bioluminescent or fluorescent reporter proteins can be used both to monitor the spatial and temporal progression of Nipah virus (NiV) infection in vivo as well as in ex vivo tissues. Virally produced luciferases react with systemically administered substrate to produce bioluminescence that can then be detected via IVIS imaging, while fluorescent reporters inherently generate detectable fluorescence without a substrate. Here we describe protocols applying bioluminescent or fluorescent reporter expressing recombinant viruses to in vivo or ex vivo imaging of NiV infection.
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Infecções por Henipavirus , Orthopoxvirus , Animais , Diagnóstico por Imagem , Corantes , Modelos AnimaisRESUMO
Although pre-exposure prophylaxis (PrEP) is an efficacious biomedical intervention, the effectiveness of same-day PrEP programs has not been widely studied. We utilized data from three of the four largest PrEP providers in Mississippi from September 2018 to September 2021 linked to the Mississippi State Department of Health's Enhanced HIV/AIDS reporting system. HIV diagnosis was defined as testing newly positive for HIV at least 2 weeks after the initial PrEP visit. We calculated the cumulative incidence and incidence rate of HIV per 100 person-years (PY). Person-time was calculated as time from the initial PrEP visit to (1) HIV diagnosis or (2) December 31, 2021 (HIV surveillance data end date). We did not censor individuals if they discontinued PrEP to obtain an estimate of PrEP effectiveness rather than efficacy. Among the 427 clients initiating PrEP during the study period, 2.3% [95% confidence interval (CI): 0.9-3.8] subsequently tested positive for HIV. The HIV incidence rate was 1.18 per 100 PY (95% CI: 0.64-2.19) and median time to HIV diagnosis after the initial PrEP visit was 321 days (95% CI: 62-686). HIV incidence rates were highest among transgender and nonbinary individuals [10.35 per 100 PY (95% CI: 2.59-41.40)] compared with cisgender men and women, and among people racialized as Black [1.45 per 100 PY (95% CI: 0.76-2.80)] compared with White and other racialized groups. These findings indicate a need for more clinical and community interventions that support PrEP persistence and restarts among those at high risk of HIV acquisition.
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Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Pessoas Transgênero , Masculino , Humanos , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Incidência , Homossexualidade Masculina , Fármacos Anti-HIV/uso terapêuticoRESUMO
The common marmoset (Callithrix jacchus) is increasingly recognized as an ideal nonhuman primate (NHP) at high biocontainment due to its smaller size and relative ease of handling. Here, we evaluated the susceptibility and pathogenesis of Nipah virus Bangladesh strain (NiVB) infection in marmosets at biosafety level 4. Infection via the intranasal and intratracheal route resulted in fatal disease in all 4 infected marmosets. Three developed pulmonary edema and hemorrhage as well as multifocal hemorrhagic lymphadenopathy, while 1 recapitulated neurologic clinical manifestations and cardiomyopathy on gross pathology. Organ-specific innate and inflammatory responses were characterized by RNA sequencing in 6 different tissues from infected and control marmosets. Notably, a unique transcriptome was revealed in the brainstem of the marmoset exhibiting neurological signs. Our results provide a more comprehensive understanding of NiV pathogenesis in an accessible and novel NHP model, closely reflecting clinical disease as observed in NiV patients.
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Infecções por Henipavirus , Vírus Nipah , Edema Pulmonar , Animais , Callithrix , BangladeshRESUMO
Pre-exposure prophylaxis (PrEP) persistence is suboptimal in the United States. In the Deep South, a region with high rates of new HIV diagnosis, patterns of PrEP discontinuation remain unexplored. We evaluated data from a clinic-based PrEP program in Jackson, Mississippi and included patients initiating PrEP between August 2018 and April 2021. We considered patients to have a gap in PrEP coverage if they had at least 30 days without an active PrEP prescription; those who restarted PrEP after 30 days were classified as 'stopped and restarted' and those who never obtained a new PrEP prescription were classified as 'stopped and did not restart'. Patients without a gap in coverage were considered 'continuously on PrEP'. We estimated median time to first PrEP discontinuation and examined factors associated with time to first PrEP discontinuation. Of 171 patients who received an initial 90-day PrEP prescription; 75% were assigned male at birth and 74% identified as Black. The median time to first discontinuation was 90 days (95% CI 90-114). Twenty-two percent were continuously on PrEP, 28% stopped and restarted (median time off PrEP = 102 days), and 50% stopped and did not restart. Associations with early PrEP stoppage were notable for patients assigned sex female vs male (adjusted hazard ratio [aHR] = 1.6, 95% CI 1.0-2.5) and those living over 25 miles from clinic vs. 0-10 miles (aHR 1.89, 95% CI 1.2-3.0). Most patients never refilled an initial PrEP prescription though many patients re-started PrEP. Interventions to improve persistence and facilitate re-starts are needed.
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Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Recém-Nascido , Humanos , Masculino , Estados Unidos , Feminino , Mississippi/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Homossexualidade MasculinaRESUMO
The family of caspases is known to mediate many cellular pathways beyond cell death, including cell differentiation, axonal pathfinding, and proliferation. Since the identification of the family of cell death proteases, there has been a search for tools to identify and expand the function of specific family members in development, health, and disease states. However, many of the currently commercially available caspase tools that are widely used are not specific for the targeted caspase. In this report, we delineate the approach we have used to identify, validate, and target caspase-9 in the nervous system using a novel inhibitor and genetic approaches with immunohistochemical read-outs. Specifically, we used the retinal neuronal tissue as a model to identify and validate the presence and function of caspases. This approach enables the interrogation of cell-type specific apoptotic and non-apoptotic caspase-9 functions and can be applied to other complex tissues and caspases of interest. Understanding the functions of caspases can help to expand current knowledge in cell biology, and can also be advantageous to identify potential therapeutic targets due to their involvement in disease.
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Caspases , Retina , Apoptose , Caspase 3/metabolismo , Caspase 9/metabolismo , Caspases/metabolismo , Diferenciação Celular , Sistema Nervoso , Retina/metabolismoRESUMO
Newman and Cain (Newman, Cain 2014 Psychol. Sci. 25, 648-655 (doi:10.1177/0956797613504785)) reported that observers view a person's choices as less ethical when that person has acted in response to both altruistic and selfish (commercial) motivations, as compared with purely selfish interests. The altruistic component reduces the observers' approval rather than raising it. This puzzling phenomenon termed the 'tainted altruism' effect, has attracted considerable interest but no direct replications in prior research. We report direct replications of Newman and Cain's Experiments 2 and 3, using a larger sample (n = 501) intended to be fairly representative of the US population. The results confirm the original findings in considerable detail.
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HIV incidence among African American (AA) young men who have sex with men (YMSM) has remained stable even though they made up the largest number of new HIV diagnoses among men who have sex with men (MSM) in 2017. HIV spreads at increased rates in dense sexual networks. Identifying the location of risk behaviors "activity spaces" could inform geographically circumscribed HIV prevention interventions. Utilizing the modified social ecological model we completed five semi-structured focus groups incorporating a modified social mapping technique, based on Singer et al.'s approach. Participants included 27 AA YMSM. Focus groups explored how and where HIV transmission happens in Jackson, Mississippi. Result themes included: 1) location of sexual behaviors, 2) knowledge of geographic hotspots of HIV infection in Jackson, and 3) traveling to meet partners: at home and away. HIV transmission or "activity spaces" may be occurring outside identified HIV hot spots. Mixed geospatial and qualitative methods offered a comprehensive assessment of where HIV transmission occurs, and suggests that geographically circumscribed interventions may need to focus on where individuals living with HIV reside and in specific geographic locations where they engage in behaviors that raise their HIV acquisition risks.
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Infecções por HIV , Minorias Sexuais e de Gênero , Geografia , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Assunção de Riscos , Comportamento Sexual , Rede SocialRESUMO
Over the past 20 years, Nipah virus (NiV) has emerged as a significant, highly pathogenic bat-borne paramyxovirus causing severe respiratory disease and encephalitis in humans, and human-to-human transmission has been demonstrated in multiple outbreaks. In addition to causing serious illness in humans, NiV is a zoonotic pathogen capable of infecting a wide range of other mammalian species, including pigs and horses. While NiV has caused less than 700 human cases since its discovery in 1998/1999, the involvement of intermediate agricultural hosts can result in significant economic consequences. Owing to the severity of disease, capacity for human-to-human transmission, zoonotic potential, and lack of available approved therapeutic treatment options, NiV has been listed by the World Health Organization in their Blueprint list of priority pathogens as one of the eight most dangerous pathogens to monitor and prepare countermeasures to prevent a pandemic. Here, we discuss progress towards the development of therapeutic measures for the treatment of NiV infection and disease.
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Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus with a wide host range including ruminants and humans. RVFV outbreaks have had devastating effects on public health and the livestock industry in African countries. However, there is no approved RVFV vaccine for human use in non-endemic countries and no FDA-approved antiviral drug for RVFV treatment. The RVFV 78kDa protein (P78), which is a membrane glycoprotein, plays a role in virus dissemination in the mosquito host, but its biological role in mammalian hosts remains unknown. We generated an attenuated RVFV MP-12 strain-derived P78-High virus and a virulent ZH501 strain-derived ZH501-P78-High virus, both of which expressed a higher level of P78 and carried higher levels of P78 in the virion compared to their parental viruses. We also generated another MP-12-derived mutant virus (P78-KO virus) that does not express P78. MP-12 and P78-KO virus replicated to similar levels in fibroblast cell lines and Huh7 cells, while P78-High virus replicated better than MP-12 in Vero E6 cells, fibroblast cell lines, and Huh7 cells. Notably, P78-High virus and P78-KO virus replicated less efficiently and more efficiently, respectively, than MP-12 in macrophage cell lines. ZH501-P78-High virus also replicated poorly in macrophage cell lines. Our data further suggest that inefficient binding of P78-High virus to the cells led to inefficient virus internalization, low virus infectivity and reduced virus replication in a macrophage cell line. P78-High virus and P78-KO virus showed lower and higher virulence than MP-12, respectively, in young mice. ZH501-P78-High virus also exhibited lower virulence than ZH501 in mice. These data suggest that high levels of P78 expression attenuate RVFV virulence by preventing efficient virus replication in macrophages. Genetic alteration leading to increased P78 expression may serve as a novel strategy for the attenuation of RVFV virulence and generation of safe RVFV vaccines.
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Macrófagos/virologia , Febre do Vale de Rift/virologia , Vírus da Febre do Vale do Rift/fisiologia , Proteínas do Envelope Viral/metabolismo , Replicação Viral/fisiologia , Animais , Camundongos , Vírus da Febre do Vale do Rift/patogenicidade , Proteínas do Envelope Viral/genética , VirulênciaRESUMO
Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Middle East that can affect humans and ruminant livestock. Currently, there are no approved vaccines or therapeutics for the treatment of severe RVF disease in humans. Tilorone-dihydrochloride (Tilorone) is a broad-spectrum antiviral candidate that has previously shown efficacy against a wide range of DNA and RNA viruses, and which is clinically utilized for the treatment of respiratory infections in Russia and other Eastern European countries. Here, we evaluated the antiviral activity of Tilorone against Rift Valley fever virus (RVFV). In vitro, Tilorone inhibited both vaccine (MP-12) and virulent (ZH501) strains of RVFV at low micromolar concentrations. In the mouse model, treatment with Tilorone significantly improved survival outcomes in BALB/c mice challenged with a lethal dose of RVFV ZH501. Treatment with 30 mg/kg/day resulted in 80% survival when administered immediately after infection. In post-exposure prophylaxis, Tilorone resulted in 30% survival at one day after infection when administered at 45 mg/kg/day. These findings demonstrate that Tilorone has potent antiviral efficacy against RVFV infection in vitro and in vivo and supports further development of Tilorone as a potential antiviral therapeutic for treatment of RVFV infection.
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BACKGROUND: Many US health departments now integrate HIV-related outcomes (e.g., relinkage to HIV care and preexposure prophylaxis [PrEP]) into sexually transmitted disease (STD) partner services (PS) programs. We sought to determine the barriers, facilitators, and cost of integrating these activities into PS. METHODS: From 2016 to 2018, the Mississippi State Department of Health integrated 3 new activities into STD PS: HIV testing for partners of HIV-negative men who have sex with men with gonorrhea/chlamydia, relinkage to HIV care for STD PS recipients previously diagnosed with HIV, and PrEP referrals. We conducted direct observations and interviews with disease intervention specialists (DIS) in Jackson to assess barriers and facilitators to implementing these activities. We completed time and motion studies with 8 DIS and case tracking forms for 90 unique cases to estimate the incremental staff time and associated personnel cost of added services compared with a standard PS case. RESULTS: Disease intervention specialists were optimistic about integrating HIV-related activities but noted disparate data systems, nonsystematic documentation, and lack of training as barriers. The mean time for a standard STD PS case without HIV-related activities was 195 minutes (cost, $77.69/case). The cost to conduct PS for HIV-negative men who have sex with men with gonorrhea/chlamydia was 36% higher than a standard case. Integrating relinkage to care and PrEP referrals resulted in a 44% and 20% increase in cost, respectively. CONCLUSIONS: Integrating HIV care relinkage and PrEP referrals into STD partner services was generally acceptable by DIS and added marginal cost per case. Coupling these cost metrics with an assessment of the effectiveness of these activities can inform prioritization of partner services activities.
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Infecções por HIV , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Sífilis , Busca de Comunicante , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Mississippi/epidemiologia , Parceiros Sexuais , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Sífilis/epidemiologiaRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Central nervous system ischemic injury features neuronal dysfunction, inflammation and breakdown of vascular integrity. Here we show that activation of endothelial caspase-9 after hypoxia-ischemia is a critical event in subsequent dysfunction of the blood-retina barrier, using a panel of interrelated ophthalmic in vivo imaging measures in a mouse model of retinal vein occlusion (RVO). Rapid nonapoptotic activation of caspase-9 and its downstream effector caspase-7 in endothelial cells promotes capillary ischemia and retinal neurodegeneration. Topical eye-drop delivery of a highly selective caspase-9 inhibitor provides morphological and functional retinal protection. Inducible endothelial-specific caspase-9 deletion phenocopies this protection, with attenuated retinal edema, reduced inflammation and preserved neuroretinal morphology and function following RVO. These results reveal a non-apoptotic function of endothelial caspase-9 which regulates blood-retina barrier integrity and neuronal survival, and identify caspase-9 as a therapeutic target in neurovascular disease.
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Caspase 9/metabolismo , Hipóxia/metabolismo , Isquemia/metabolismo , Oclusão da Veia Retiniana/metabolismo , Lesões do Sistema Vascular/metabolismo , Animais , Barreira Hematorretiniana/metabolismo , Caspase 7/metabolismo , Caspase 9/efeitos dos fármacos , Caspase 9/genética , Morte Celular , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Feminino , Predisposição Genética para Doença/genética , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Coelhos , Retina/metabolismo , Retina/patologia , Oclusão da Veia Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/patologia , Lesões do Sistema Vascular/patologiaRESUMO
Mississippi has one of the highest rates of HIV in the United States, but has low pre-exposure prophylaxis (PrEP) uptake, particularly among black men who have sex with men (MSM) and women. From November 2018 to May 2019, patients at high risk of HIV who tested negative for HIV at a nonclinical testing center in Jackson, Mississippi, were referred to an on-site clinical pharmacist for same-day PrEP initiation. The pharmacist evaluated patients for medical contraindications to PrEP, but no baseline labs were obtained. The pharmacist provided a PrEP prescription and scheduled a clinical appointment for patients within 6 weeks, at which time they were evaluated by a clinician and completed baseline labs. The pharmacist evaluated 69 patients for PrEP; 57% were MSM, 77% were black, and 65% were uninsured. All patients received a PrEP prescription; 83% received the prescription the same day and 97% received it within 5 days. Fifty-three (77%) of 69 clients filled the prescription; 87% of whom filled it within 1 week. Only 23 (43%) of 53 clients who filled their prescription attended their initial clinical appointment within 6 weeks of obtaining PrEP. There were no differences in PrEP initiation or retention by patient sex/gender. This pilot program suggests that an on-site pharmacist working in a nonclinical testing center in the southern United States can successfully initiate PrEP among predominately low-income black MSM. Future efforts should seek to better integrate laboratory testing into this demedicalized model of PrEP and to improve retention in care.
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Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/prevenção & controle , Farmacêuticos , Profilaxia Pré-Exposição/métodos , Adolescente , Adulto , Cognição , Feminino , Infecções por HIV/tratamento farmacológico , Homossexualidade Masculina , Humanos , Masculino , Mississippi , Projetos Piloto , Profilaxia Pré-Exposição/organização & administração , Estados Unidos , Adulto JovemRESUMO
Several members of the tripartite motif (TRIM) family of E3 ubiquitin ligases regulate immune pathways, including the antiviral type I interferon (IFN-I) system. Previously, we demonstrated that TRIM6 is involved in IFN-I induction and signaling. In the absence of TRIM6, optimal IFN-I signaling is reduced, allowing increased replication of interferon-sensitive viruses. Despite having evolved numerous mechanisms to restrict the vertebrate host's IFN-I response, West Nile virus (WNV) replication is sensitive to pretreatment with IFN-I. However, the regulators and products of the IFN-I pathway that are important in regulating WNV replication are incompletely defined. Consistent with WNV's sensitivity to IFN-I, we found that in TRIM6 knockout (TRIM6-KO) A549 cells, WNV replication is significantly increased and IFN-I induction and signaling are impaired compared to wild-type (wt) cells. IFN-ß pretreatment was more effective in protecting against subsequent WNV infection in wt cells than TRIM6-KO, indicating that TRIM6 contributes to the establishment of an IFN-induced antiviral response against WNV. Using next-generation sequencing, we identified VAMP8 as a potential factor involved in this TRIM6-mediated antiviral response. VAMP8 knockdown resulted in reduced JAK1 and STAT1 phosphorylation and impaired induction of several interferon-stimulated genes (ISGs) following WNV infection or IFN-ß treatment. Furthermore, VAMP8-mediated STAT1 phosphorylation required the presence of TRIM6. Therefore, the VAMP8 protein is a novel regulator of IFN-I signaling, and its expression and function are dependent on TRIM6 activity. Overall, these results provide evidence that TRIM6 contributes to the antiviral response against WNV and identify VAMP8 as a novel regulator of the IFN-I system.IMPORTANCE WNV is a mosquito-borne flavivirus that poses a threat to human health across large discontinuous areas throughout the world. Infection with WNV results in febrile illness, which can progress to severe neurological disease. Currently, there are no approved treatment options to control WNV infection. Understanding the cellular immune responses that regulate viral replication is important in diversifying the resources available to control WNV. Here, we show that the elimination of TRIM6 in human cells results in an increase in WNV replication and alters the expression and function of other components of the IFN-I pathway through VAMP8. Dissecting the interactions between WNV and host defenses both informs basic molecular virology and promotes the development of host- and virus-targeted antiviral strategies.
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Imunidade Inata , Interferon Tipo I/imunologia , Proteínas R-SNARE/imunologia , Proteínas com Motivo Tripartido/imunologia , Ubiquitina-Proteína Ligases/imunologia , Replicação Viral/imunologia , Febre do Nilo Ocidental/imunologia , Vírus do Nilo Ocidental/fisiologia , Células A549 , Deleção de Genes , Células HEK293 , Humanos , Janus Quinase 1/genética , Janus Quinase 1/imunologia , Fosforilação/genética , Fosforilação/imunologia , Proteínas R-SNARE/genética , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/imunologia , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Replicação Viral/genética , Febre do Nilo Ocidental/genética , Febre do Nilo Ocidental/patologiaRESUMO
Syphilis and HIV are important public health issues in the United States, especially in the southeastern region. This study aimed to determine and describe the co-infection pattern in Mississippi by using a case-controlled design to analyze cases diagnosed with syphilis or HIV from 2007 to 2016. Direct matching was employed to identify cases that were co-infected during the same calendar year, and binary logistic regression analysis was used to determine predictors of co-infection. Results showed that 1736 (34.0%) of syphilis and HIV cases were co-infected during the same calendar year. Binary logistic regression results demonstrated that race, gender, age group, and exposure category were independently associated with co-infection status. These analyses highlighted the progressive increase of co-infection rates in Mississippi. Collaboration between STI/HIV surveillance teams may identify high-risk individuals and reduce transmission of both diseases.
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Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Sífilis/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Infecções por HIV/diagnóstico , Humanos , Lactente , Recém-Nascido , Masculino , Mississippi/epidemiologia , Fatores de Risco , Sífilis/diagnósticoRESUMO
The Medical Monitoring Project (MMP) is an HIV surveillance system that provides national estimates of HIV-related behaviors and clinical outcomes. When first implemented, MMP excluded persons living with HIV not receiving HIV care. This analysis will describe new case-surveillance-based methods to identify and recruit persons living with HIV who are out of care and at elevated risk for mortality and ongoing HIV transmission. Stratified random samples of all persons living with HIV were selected from the National HIV Surveillance System in five public health jurisdictions from 2012-2014. Sampled persons were located and contacted through seven different data sources and five methods of contact to collect interviews and medical record abstractions. Data were weighted for non-response and case reporting delay. The modified sampling methodology yielded 1159 interviews (adjusted response rate, 44.5%) and matching medical record abstractions for 1087 (93.8%). Of persons with both interview and medical record data, 264 (24.3%) would not have been included using prior MMP methods. Significant predictors were identified for successful contact (e.g., retention in care, adjusted Odds Ratio [aOR] 5.02; 95% Confidence Interval [CI] 1.98-12.73), interview (e.g. moving out of jurisdiction, aOR 0.24; 95% CI: 0.12-0.46) and case reporting delay (e.g. rural residence, aOR 3.18; 95% CI: 2.09-4.85). Case-surveillance-based sampling resulted in a comparable response rate to existing MMP methods while providing information on an important new population. These methods have since been adopted by the nationally representative MMP surveillance system, offering a model for public health program, research and surveillance endeavors seeking inclusion of all persons living with HIV.