Search Results (225)

Current structural barriers experienced by First Nations in Canada shape access and engagement for testing and treatment of hepatitis C virus (HCV) infections. This non-systematic informative review considers transdisciplinary perspectives, regional data, and published literature connecting context to the disproportionate HCV burden experienced by First Nations populations in the prairie provinces of Canada, and offers examples of participatory and community-led initiatives working toward the elimination of HCV as a public health threat. First Nations in Canada are disproportionately impacted by chronic HCV infection, with a reported rate of newly diagnosed HCV cases in First Nations communities five times the respective rate in the general Canadian population in 2022. This review explores the reasons underlying the disproportionate burden of HCV infection. Significant over-representation of First Nations in the Canadian Prairies is seen in the major risk categories for HCV acquisition, and the impact of these risk factors is aggravated by barriers to accessing healthcare services and medication coverage. These barriers stem from the legacy of colonialism, discrimination, disenfranchisement, and are exacerbated by stigmatization, victimization, and racism in the justice and healthcare systems. Other contributory factors that impede access to care include inadequate healthcare clinic staffing and infrastructure in First Nations communities, and significant geographical distances between First Nations reserves and laboratories, pharmacies, and treating/prescribing healthcare providers. Recent recognition of historical harms and early steps towards nation-to-nation reconciliation, along with support for culturally connected, holistic, and First Nations-led wellness programs, instill hope that elimination strategies to eradicate HCV infection in First Nations populations will be successful in Canada. Full article

Background/Objectives: Contextual memory associated with methamphetamine (METH) use contributes to relapse and persistence of addiction. Angiotensin II type 1 receptor (AT1R) signaling has been implicated in drug reinforcement. LCZ696, a clinically used combination of sacubitril (a neprilysin inhibitor) and valsartan (an AT1R antagonist), may interfere with METH-associated memory through the modulation of dopaminergic pathways. Methods: Male C57BL/6J mice were tested in a conditioned place preference (CPP) paradigm to assess the effects of LCZ696, sacubitril (AHU377), and valsartan on METH-induced memory expression and reinstatement. Synaptic plasticity in the nucleus accumbens (NAc) was examined by assessing the levels of synaptophysin (Syp) and postsynaptic density protein 95 (Psd95), as well as dendritic spine density. Dopaminergic signaling in the ventral tegmental area (VTA) was evaluated via ELISA, Western blotting, and chromatin immunoprecipitation (ChIP), targeting cAMP response element-binding protein (Creb) binding to the tyrosine hydroxylase (Th) promoter. To further assess the role of Th, an adeno-associated virus (AAV9) carrying a CRISPR-Cas9-based sgRNA targeting Th (AAV9-Th-sgRNA) was microinjected into the VTA. Results: LCZ696 and valsartan significantly reduced METH-induced CPP and reinstatement. LCZ696 reversed METH-induced synaptic and dopaminergic alterations and suppressed Creb-mediated Th transcription. Th knockdown attenuated both CPP acquisition and relapse. Conclusions: LCZ696 disrupts METH-associated contextual memory by modulating dopaminergic signaling and Creb-dependent Th expression, supporting its potential as a treatment for METH use disorder. Full article

Virus-like particles (VLPs) have the potential to become a versatile carrier platform for vaccination against multiple diseases. In the light of short process development timelines and the demand for reliable and robust processes, metabolic modeling of cell culture processes offers great advantages when coupled with a Quality-by-Design (QbD) development approach. A previous work was able to demonstrate the accurate prediction of HEK293F PiggyBac cell concentration as well as VLP titer and metabolite production with a reduced metabolic model. This work presents the reduced metabolic model for a more productive cell line Sleeping Beauty and emphasizes the need for model re-parameterization when the producer cell line changes. The goal of precise prediction for a fed-batch and continuous HEK293 cultivation can, therefore, be achieved. In terms of decision-making for downstream unit operations, a soft sensor for the prediction of main impurities like proteins and DNA was introduced for the first time for the production of lentiviral vectors with several terms describing the release of impurities like DNA and proteins, growth-related protein production, and enzymatic degradation activity associated with cell dissociation in an accurate manner. The additional information can contribute to a more efficient design phase by reducing experimental effort as well as during cultivation with data-based decision-making. With the aid of real-time process data acquisition through process analytical technology (PAT), its predictive power can be enhanced and lead to more reliable processes. Full article

Infants born to HIV-positive mothers remain at significant risk of HIV acquisition despite maternal adherence to antiretroviral therapy, cesarean delivery, and formula feeding. Our previous study reported that initiating early antiretroviral treatment at three days post-SIV infection resulted in approximately eighty percent of pediatric virologic remission. In this study, we investigated treatment outcomes in postnatally SHIV-exposed infant macaques when early intervention was delayed by two days, as well as the mechanisms underlying virologic control. The results showed that, although initiating treatment at five days post-exposure effectively suppressed viral replication, only one of the three infant macaques achieved a sustained state of virologic remission following analytical treatment interruption. Notably, this virus-controlled infant lacked detectable virus-specific immunity, including neutralizing antibodies, cytotoxic T cell responses, and antibody-dependent cellular cytotoxicity. These findings highlight the critical importance of early treatment initiation as a key determinant of virologic control in HIV-exposed, infected infants. This study provides valuable insights for guiding early pediatric HIV intervention strategies in clinical settings. Full article

The ability of a virus to be propagated within a host cell is dependent on a multitude of dynamic virus–host interactions. Live-cell imaging is an invaluable approach in the study of virus replication cycles and virus–host interactions as it can allow for the direct visualisation of key events and interactions in real time. These details can provide unique insights into many aspects of viral infections including the cellular pathways that are exploited by viruses, the evasion of host immune defences, and viral pathogenesis. This review summarises the live-cell fluorescence imaging approaches that have been developed and applied to study Flaviviridae virus family members that are responsible for significant public health burdens and outbreaks which, in many instances, are increasing in frequency and severity. We discuss how these approaches have expanded our understanding of fundamental stages of viral replication cycles by enabling the direct visualisation of the localisation, trafficking, and interactions of virus particles, proteins, and genomes at distinct stages. The strategies that can be employed to enhance the biological relevance of live-cell fluorescence imaging acquisitions are discussed, along with how live-cell imaging approaches can be further developed to increase resolution, enable multi-colour imaging, and support the long-term visualisation of multiple stages of a viral replication cycle. Full article

Tomato yellow leaf curl disease poses one of the most severe threats to tomato production worldwide. This disease is associated with a group of closely related tomato yellow leaf curl viruses. These viruses can be transmitted by the sweet potato whitefly (Bemisia tabaci) in a persistent-circulative mode. Virus particles can infect the midgut and filter chamber of whiteflies feeding on infected plants, circulate in the hemolymph, and eventually infect the primary salivary gland (PSG) of whiteflies. Later, the whiteflies feed on healthy plants, and viral particles are introduced into the plants through their saliva. Virus–vector interactions play a crucial role in the efficiency and dynamics of virus transmission. In this study, we assessed the effects of the acquisition time and viral load of source plants on infections of two tomato begomoviruses, tomato yellow leaf curl Thailand virus (TYLCTHV) and tomato leaf curl Taiwan virus (ToLCTV), in B. tabaci Middle East–Asia Minor 1. We found that more viruses were acquired and accumulated in the whitefly midgut and PSG before reaching a plateau when the acquisition time increased and when the source plant had a higher viral load. The midgut and PSG acquired and accumulated more TYLCTHV than ToLCTV with the same acquisition time and regardless of the viral loads in coinfected source plants. These results not only help us to understand virus–vector interactions but also help in developing integrated disease management strategies. Full article

This study proposes a novel virus propagation model designed explicitly for SCADA(supervisory Control and Data Acquisition) industrial networks. It addresses a critical limitation in existing models applied to the Internet and Industrial Internet of Things (IIoT)—their failure to account for inter-node information exchange processes. The model is inspired by the phenomenon that “immune” nodes in real-world and biological systems inhibit the spread of viruses by exchanging information. This model incorporates isolation strategies to curb virus transmission, considering the uncertainty of vulnerable device behavior. Central to this research are the assumptions of a nonlinear infection rate and dual delays, which better mirror the real-world conditions of industrial control networks. This approach diverges significantly from prior studies that relied on bilinear infection rate assumptions. This study constructed an SMIQR model through theoretical derivation and experimental validation. The model enables nodes to autonomously enhance their defenses after receiving risk information while accounting for the impact of inter-node information exchange. Experiments based on real-world data demonstrated the model’s effectiveness in simulating virus propagation and evaluating defense strategies, overcoming the limitations of traditional bilinear infection rate assumptions. Comparative experiments show that the SMIQR model significantly reduces the number of infected nodes in SCADA industrial networks, demonstrating its superior effectiveness in curbing virus spread. Furthermore, the research proposed dynamic isolation tactics that balance industrial operational continuity, providing SCADA industrial networks with a theoretical framework (incorporating nonlinear infection rates and dual delay characteristics) and practical defense solutions to curb malware spread without disrupting production. Full article

(1) Background: The ongoing panzootic of highly pathogenic avian influenza virus (HPAIV) of subtype H5N1, clade 2.3.4.4b, has decimated wild/domestic birds and mammals’ populations worldwide with reports of sporadic cases in humans. (2) Methods: This study aimed to compare the mutational profile of H5N1 avian Influenza virus isolated from a Peruvian natural reserve, with recent data from other related international studies made in human and different species of domestic and wild birds and mammals. Briefly, the near complete protein sequences of the Influenza virus coming from a Calidris alba were analyzed at a multisegmented level, together with 55 samples collected between 2022 and 2024 in different countries. Moreover, the glycosylation patterns were also predicted in silico. (3) Results: A total of 603 amino acid changes were found among H5N1 viruses analyzed, underscoring the detection of critical mutations HA:11I, HA:211I, HA:336T, HA:492D, HA:527I, NA:10T, NA:269L, NA:405T, NP:377N, PA:57R, PA:68S, PA:322V/L, PA:432I, PB2:539V, PB1:207R, PB1:375N, PB1:264D, PB1:429R, PA-X:250Q, PB1-F2:65R, and PB1-F2:42Y, as well as PA:13V, PA-X:13V, PA20T, PA-X:20T, PA:36T PA-X:36T, PA:45S, PA-X:45S, PA:57Q, PA-X:57Q, PA:61I, PA-X:61I, PA:68S, PA-X:68S, PA:70V, PA-X:70V, PA:75Q, PA-X:75Q, PA:85T, PA-X:85T, PA:86I, PA-X:86I, PA:100I, PA-X:100I, PA:142E, PA-X:142E, PA:160E, PA-X:160E, PA:211I, PA-X:211Y, among others, considered of importance under the One Health perspective. Similarly, changes in the N-linked glycosylation sites (NLGs) predicted in both HA and NA proteins were found, highlighting the loss/acquisition or changes in some NLGs, such as 209NNTN, 100 NPTT, 302NSSM (HA) and 70NNTN, 68NISS, and 50NGSV (NA). (4) Conclusions: This study provides our understanding about the evolution of current Influenza A viruses H5N1 HPAIV circulating globally. These findings outline the importance of surveillance updating mutational profiles and glycosylation patterns of these highly evolved viruses. Full article

Sulfate transporters (SULTRs) are key players that regulate sulfur acquisition and distribution within plants, thereby influencing cellular redox hemostasis under pathogen attacks, such as Alternaria brassicicola (Ab). In this study, a total of 23 BolSULTR (Brassica oleracea SULTR) genes were identified from the Brassica genome. These BolSULTRs are distributed across nine chromosomes, with all collinear BolSULTR gene pairs undergoing purifying selections. Phylogenetic analysis reveals that the SULTR family is evolutionarily conserved among plant kingdoms. qRT-PCR analysis demonstrated that the expression of BolSULTRs varies across different plant organs and is modulated by hormonal signals. Furthermore, transcriptome analysis identified several BolSULTRs whose expression levels were depressed in Ab-challenged leaves in broccoli. Among them, the BolSULTR2;1 gene emerged as a key player in the plant’s response to Ab. Virus-induced gene silencing (VIGS) of BolSULTR2;1s resulted in elevated glutathione (GSH) levels and enhanced tolerance to Ab. Taken together, these findings underscore the role of BolSULTR2;1 in maintaining redox homeostasis and enhancing plant disease resistance, suggesting its potential as a target for genome editing to develop broccoli varieties with improved pathogen tolerance. Full article

Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitos that poses a threat to global public health and for which there is an urgent need for widespread access to globally licensed vaccines. Here, we demonstrate that an inactivated CHIKV vaccine (BBV87) protects against systemic infection with CHIKV in a non-human primate (NHP) challenge model. Groups of five cynomolgus macaques received two doses of 20 µg BBV87 vaccine or saline alone (28 days apart). Twenty-eight days after the second immunisation, all animals were challenged with CHIKV. All controls were productively infected with detectable viremia and pathological responses following challenge, including altered thermoregulation, haematological and cytokine changes. Critically, the histopathological analysis of finger joints identified areas of inflammation in the synovium. By contrast vaccinated macaques had no detectable viremia and none of the pathological changes were reported in control animals. This study demonstrates that a 20 µg dose of BBV87 vaccine confers robust protection in vivo, both on the acquisition of infection and pathology. Full article

The rising incidence of oropharyngeal cancer caused by high-risk Human Papillomavirus (HPV) type 16 and HPV18 in the U.S and other developed countries is an important public health issue. This has been attributed to changes in sexual behavior, including the practice of oral sex, which may expose individuals to increased risk of acquiring oral HPV infection. The incidence of oral HPV infections highlights the role of the oral cavity as an important anatomical site in the acquisition and transmission of high-risk HPVs. Generally, the use of mouthwash/oral rinses have focused on targeting the oral bacteriome, and could additionally be formulated for managing the oral virome. Here, we examined virucidal properties of common over-the-counter antibacterial mouthwash products against native HPV16 and HPV18 virion in vitro, and downstream modification of virus infectivity. We tested oral rinses containing essential oils/alcohol, hydrogen peroxide, and cetylpyridinium chloride. Our results demonstrated greater than 90% efficacy against HPV16 inactivation, but comparatively with less efficacy against HPV18. Overall, hydrogen peroxide containing oral rinses demonstrated the best efficacy against both high-risk types, albeit with lower efficacy against HPV18. Prophylactic virucidal oral rinses targeted towards high-risk HPVs could be beneficial in reducing incidental oral HPV load, prevalence, and persistent infections. Full article

Background/Objectives: The development of an effective HIV vaccine has faced persistent challenges, as evidenced by the recent discontinuation of the Mosaico phase 3 trial. This study aims to critically examine the obstacles encountered in HIV vaccine development, with a focus on the Mosaico trial, which tested the Ad26.Mos4.HIV vaccine among 3,900 participants across multiple countries. We also explore emerging vaccine technologies and their potential in overcoming these challenges, while reflecting on lessons from previous trials to inform future strategies. Methods: We reviewed the Mosaico trial’s approach, which involved testing the efficacy of the Ad26.Mos4.HIV vaccine. We compared the outcomes of the Mosaico trial with other major HIV vaccine trials, including HVTN 702, Imbokodo, and RV144. We explored the limitations of the immune responses elicited by the Mosaico vaccine. The review focused on the generation of broadly neutralizing antibodies (bNAbs) and the challenges related to antigenic diversity and B-cell engagement. Emerging vaccine technologies, such as virus-like particles (VLPs), nanoparticles, SOSIP trimers, and mRNA platforms, were also analysed for their scalability, immune durability, and potential to advance HIV vaccine development. Results: The Mosaico trial was discontinued due to insufficient efficacy in reducing HIV acquisition, primarily due to the inability of the vaccine to induce bNAbs, which are crucial for targeting the diverse HIV-1 strains. A major challenge was the inadequate engagement of germline B-cell precursors, compounded by the antigenic diversity of the virus. The analysis showed that emerging vaccine platforms, such as VLPs, nanoparticles, SOSIP trimers, and mRNA-based approaches, hold promise but present challenges related to scalability and the durability of immune responses. The role of T cells and adjuvants in enhancing vaccine efficacy was also highlighted as critical for integrating both humoral and cellular immunity. Conclusions: The Mosaico trial, as well as other major HIV vaccine trials, underscores the need for a multi-pronged approach that incorporates both antibody and T-cell responses to tackle the complexities of HIV-1. Future efforts in HIV vaccine development must focus on inducing bNAbs, generating robust T-cell responses, and utilizing scalable vaccine platforms. The integration of artificial intelligence (AI) into vaccine design offers new opportunities to optimize immunogenic targets, which could significantly improve the potential for durable and broad immune protection. The development of a successful HIV vaccine by 2030 is achievable but relies on leverage on advanced technologies including artificial intelligence, innovation and insights from past trial data. Full article

Background: Sex work is one of the oldest trades in the world. It is the practice of sexual activity in exchange for money or material goods. It has traditionally been carried out by women, although in recent years, there has been an increase in the number of male sex workers. Sex workers have been recognized as a population at high risk of contracting and transmitting sexually transmitted infections and human immunodeficiency virus and have had limited access to multiple services, including health care. Objective: The aim was to identify the epidemiological profile and risk factors of a population of sex workers in the province of Granada, southern Spain. Methods: An analytical cross-sectional study was conducted by reviewing the medical records at a specific sexually transmitted infection center in Spain. Results: A total of 157 sex workers’ records were analyzed, most of whom were women, who mainly identified as heterosexual, with a mean age of 28.52 years and a high percentage of foreign nationality. Some sexual behaviors associated with the acquisition of sexually transmitted infections were also analyzed. Conclusions: The results revealed a deficient coverage of the health needs of a highly vulnerable and stigmatized social group, highlighting the need for interventions to prevent risky habits, as well as to promote behaviors aimed at achieving better sexual health. Full article

Syphilis and other sexually transmitted infections (STIs) are highly prevalent in most regions experiencing severe human immunodeficiency virus (HIV) epidemics. In sub-Saharan Africa, the region most heavily affected by HIV, the prevalence of syphilis among people living with HIV (PLWH) is notably high. This region accounts for 40% of global STIs and 70% of HIV cases. Despite the high prevalence of syphilis and other STIs among PLWH in the region, there are limited studies on the interplay between the two infections from the region. Most studies on the association between syphilis and HIV transmission/progression from the region are limited to specific groups of people, such as female sex workers or pregnant women. In this manuscript, we evaluated the association between the two infections using population-based surveys conducted in the region. Statistical methods (such as logistic regression models and propensity score matching) were employed to assess the interplay between the two infections. Our findings indicated that syphilis infection was associated with higher odds of HIV acquisition. Moreover, co-infection with syphilis was associated with higher odds of HIV disease progression among antiretroviral therapy (ART)-treated PLWH, though the association did not reach statistical significance. Our findings suggest that the recognition and treatment of syphilis to reduce the risk of HIV acquisition/progression should be a public health priority in sub-Saharan Africa, where ART may not be readily available. Full article

Anogenital inflammation is a critical risk factor for HIV acquisition. The primary preventative HIV intervention, pre-exposure prophylaxis (PrEP), is ineffective in blocking transmission in anogenital inflammation. Pre-existing sexually transmitted diseases (STIs) and anogenital microbiota dysbiosis are the leading causes of inflammation, where inflammation is extensive and often asymptomatic and undiagnosed. Dendritic cells (DCs), as potent antigen-presenting cells, are among the first to capture HIV upon its entry into the mucosa, and they subsequently transport the virus to CD4 T cells, the primary HIV target cells. This increased HIV susceptibility in inflamed tissue likely stems from a disrupted epithelial barrier integrity, phenotypic changes in resident DCs and an influx of inflammatory HIV target cells, including DCs and CD4 T cells. Gaining insight into how HIV interacts with specific inflammatory DC subsets could inform the development of new therapeutic strategies to block HIV transmission. However, little is known about the early stages of HIV capture and transmission in inflammatory environments. Here, we review the currently characterised inflammatory-tissue DCs and their interactions with HIV. Full article