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Future Science OA Aug 2023The 2022 monkeypox outbreak has created a new global health threat and pandemic. Monkeypox virus is a descendant of the genus , producing a febrile skin rash disease in... (Review)
Review
The 2022 monkeypox outbreak has created a new global health threat and pandemic. Monkeypox virus is a descendant of the genus , producing a febrile skin rash disease in humans. Monkeypox is zoonotic transmitted and transmitted from human to human in several ways. Even though this disease is self-limited, it creates important community health worries due to its inconvenience and widespread complications. Herein, we discussed the up-to-date current situation of monkeypox regarding its epidemiology, clinical manifestations, current in-use therapeutics, necessary protective measures, and response to potential occurrences considering the recent pandemic. Also, in this review, a comparative genomic analysis of the recent circulating strains that have been recovered from various countries including, Egypt, USA, Spain, Japan and South Africa has been investigated.
PubMed: 37485445
DOI: 10.2144/fsoa-2023-0048 -
PloS One 2023According to UNAIDS, Togo halved AIDS-related deaths among children ages 0-14 from 2010 to 2020. However, available data show low dolutegravir (DTG)-containing...
Targeted solutions to increase dolutegravir coverage, viral load testing coverage, and viral suppression among children living with HIV in Togo: An analysis of routine facility data.
BACKGROUND
According to UNAIDS, Togo halved AIDS-related deaths among children ages 0-14 from 2010 to 2020. However, available data show low dolutegravir (DTG)-containing antiretroviral therapy (ART) coverage and low viral load suppression (VLS) among children living with HIV (CLHIV). We analyzed routine facility data before and after implementation of root-cause-based solutions for improving DTG coverage, viral load (VL) testing coverage, and VLS among CLHIV.
DESCRIPTION
We analyzed routine data for CLHIV ≤14 years from October 2019 through September 2022. We assessed proportion of CLHIV on ART receiving DTG, VL testing coverage (CLHIV on ART with documented VL test result), and VLS (CLHIV with documented VL test result of <1,000 copies among those with test result). From October 2019 to September 2020, 52% were on a DTG-containing regimen, 48% had documented VL test results, and 64% had VLS. Site-level teams conducted a root-cause analysis and designed corresponding solutions implemented beginning October 2020: line listing and contacting eligible CLHIV to start/transition to DTG-containing regimen and collect VL samples; ART adherence support; monthly DTG stock monitoring; tracking pending VL test results through laboratory focal persons; documenting VL test results; and informing caregivers within one week if CLHIV not virally suppressed. Granular data were used to prioritize technical assistance to sites with lowest DTG coverage, VL testing coverage, and VLS.
RESULTS
From baseline (October 2019-September 2020) to endline (October 2021-September 2022), increases were observed for DTG coverage (52% to 71%), VL testing coverage (48% to 90%), and VLS (64% to 82%). Age-disaggregated data showed positive trends.
CONCLUSIONS
Root-cause-based solutions and granular data use increased DTG coverage, resulting in increased VL testing and VLS among CLHIV. These interventions should be scaled and become the national standard of care.
Topics: Child; Humans; Viral Load; Togo; Retrospective Studies; HIV Infections; Anti-HIV Agents
PubMed: 38128036
DOI: 10.1371/journal.pone.0296293 -
Journal of the International AIDS... Dec 2023Unhealthy alcohol use significantly contributes to viral non-suppression among persons with HIV (PWH). It is unknown whether brief behavioural interventions to reduce... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of a brief alcohol counselling intervention on HIV viral suppression and alcohol use among persons with HIV and unhealthy alcohol use in Uganda and Kenya: a randomized controlled trial.
INTRODUCTION
Unhealthy alcohol use significantly contributes to viral non-suppression among persons with HIV (PWH). It is unknown whether brief behavioural interventions to reduce alcohol use can improve viral suppression among PWH with unhealthy alcohol use in sub-Saharan Africa (SSA).
METHODS
As part of the SEARCH study (NCT04810650), we conducted an individually randomized trial in Kenya and Uganda of a brief, skills-based alcohol intervention among PWH with self-reported unhealthy alcohol use (Alcohol Use Disorders Identification Test-Consumption [AUDIT-C], prior 3 months, ≥3/female; ≥4/male) and at risk of viral non-suppression, defined as either recent HIV viral non-suppression (≥400 copies/ml), missed visits, out of care or new diagnosis. The intervention included baseline and 3-month in-person counselling sessions with interim booster phone calls every 3 weeks. The primary outcome was HIV viral suppression (<400 copies/ml) at 24 weeks, and the secondary outcome was unhealthy alcohol use, defined by AUDIT-C or phosphatidylethanol (PEth), an alcohol biomarker, ≥50 ng/ml at 24 weeks.
RESULTS
Between April and September 2021, 401 persons (198 intervention, 203 control) were enrolled from HIV clinics in Uganda (58%) and Kenya (27%) and alcohol-serving venues in Kenya (15%). At baseline, 60% were virally suppressed. Viral suppression did not differ between arms at 24 weeks: suppression was 83% in intervention and 82% in control arms (RR: 1.01, 95% CI: 0.93-1.1). Among PWH with baseline viral non-suppression, 24-week suppression was 73% in intervention and 64% in control arms (RR 1.15, 95% CI: 0.93-1.43). Unhealthy alcohol use declined from 98% at baseline to 73% in intervention and 84% in control arms at 24 weeks (RR: 0.86, 95% CI: 0.79-0.94). Effects on unhealthy alcohol use were stronger among women (RR 0.70, 95% CI: 0.56-0.88) than men (RR 0.93, 95% CI: 0.85-1.01) and among participants with a baseline PEth⩽200 ng/ml (RR 0.68, 95% CI: 0.53-0.87) versus >200 ng/ml (RR 0.97, 95% CI: 0.92-1.02).
CONCLUSIONS
In a randomized trial of 401 PWH with unhealthy alcohol use and risk for viral non-suppression, a brief alcohol intervention reduced unhealthy alcohol use but did not affect viral suppression at 24 weeks. Brief alcohol interventions have the potential to improve the health of PWH in SSA by reducing alcohol use, a significant driver of HIV-associated co-morbidities.
Topics: Humans; Male; Female; HIV Infections; Alcoholism; Uganda; Kenya; Counseling; Ethanol
PubMed: 38054564
DOI: 10.1002/jia2.26187 -
Poultry Science Jun 2024Duck Tembusu virus (DTMUV) belongs to the Flaviviridae family and mainly infects ducks. Duck Tembusu virus genome encodes one polyprotein that undergoes cleavage to...
Duck Tembusu virus (DTMUV) belongs to the Flaviviridae family and mainly infects ducks. Duck Tembusu virus genome encodes one polyprotein that undergoes cleavage to produce 10 proteins. Among these, NS4B, the largest transmembrane protein, plays a crucial role in the viral life cycle. In this study, we investigated the localization of NS4B and found that it is located in the endoplasmic reticulum, where it co-localizes with DTMUV dsRNA. Subsequently, we confirmed 5 different transmembrane domains of NS4B and discovered that only its transmembrane domain 3 (TMD3) can traverse ER membrane. Then mutations were introduced in the conserved amino acids of NS4B TMD3 of DTMUV replicon and infectious clone. The results showed that V111G, V117G, and I118G mutations enhanced viral RNA replication, while Q104A, T106A, A113L, M116A, H120A, Y121A, and A122G mutations reduced viral replication. Recombinant viruses with these mutations were rescued and studied in BHK21 cells. The findings demonstrated that A113L and H120A mutations led to higher viral titers than the wild-type strain, while Q104A, T106A, V111G, V117G, and Y121A mutations attenuated viral proliferation. Additionally, H120A, M116A, and A122G mutations enhanced viral proliferation. Furthermore, Q104A, T106A, V111G, M116A, V117G, Y121A, and A122G mutants showed reduced viral virulence to 10-d duck embryos. Animal experiments further indicated that all mutation viruses resulted in lower genome copy numbers in the spleen compared to the WT group 5 days postinfection. Our data provide insights into the topological model of DTMUV NS4B, highlighting the essential role of NS4B TMD3 in viral replication and proliferation.
Topics: Animals; Viral Nonstructural Proteins; Ducks; Flavivirus; Virus Replication; Poultry Diseases; Flavivirus Infections; Mutation
PubMed: 38652953
DOI: 10.1016/j.psj.2024.103727 -
Viruses May 2024People with HIV exhibit persistent inflammation that correlates with HIV-associated comorbidities including accelerated aging, increased risk of cardiovascular disease,... (Review)
Review
People with HIV exhibit persistent inflammation that correlates with HIV-associated comorbidities including accelerated aging, increased risk of cardiovascular disease, and neuroinflammation. Mechanisms that perpetuate chronic inflammation in people with HIV undergoing antiretroviral treatments are poorly understood. One hypothesis is that the persistent low-level expression of HIV proviruses, including RNAs generated from defective proviral genomes, drives the immune dysfunction that is responsible for chronic HIV pathogenesis. We explore factors during HIV infection that contribute to the generation of a pool of defective proviruses as well as how HIV-1 mRNA and proteins alter immune function in people living with HIV.
Topics: Humans; HIV Infections; Inflammation; HIV-1; Transcription, Genetic; Proviruses; Protein Biosynthesis; RNA, Viral
PubMed: 38793632
DOI: 10.3390/v16050751 -
Viruses Jun 2024African swine fever (ASF) is a contagious viral disease affecting pigs and wild boars. It typically presents as a hemorrhagic fever but can also manifest in various... (Review)
Review
African swine fever (ASF) is a contagious viral disease affecting pigs and wild boars. It typically presents as a hemorrhagic fever but can also manifest in various forms, ranging from acute to asymptomatic. ASF has spread extensively globally, significantly impacting the swine industry. The complex and highly variable character of the ASFV genome makes vaccine development and disease surveillance extremely difficult. The overall trend in ASFV evolution is towards decreased virulence and increased transmissibility. Factors such as gene mutation, viral recombination, and the strain-specificity of virulence-associated genes facilitate viral variations. This review deeply discusses the influence of these factors on viral immune evasion, pathogenicity, and the ensuing complexities encountered in vaccine development, disease detection, and surveillance. The ultimate goal of this review is to thoroughly explore the genetic evolution patterns and variation mechanisms of ASFV, providing a theoretical foundation for advancement in vaccine and diagnostic technologies.
Topics: African Swine Fever Virus; Animals; Swine; African Swine Fever; Genetic Variation; Genome, Viral; Virulence; Viral Vaccines; Evolution, Molecular; Immune Evasion; Mutation; Vaccine Development
PubMed: 38932205
DOI: 10.3390/v16060913 -
Virology Journal Apr 2024To determine the correlation between HPV (human papillomavirus) 52 viral load, multiple infections and ThinPrep cytology test (TCT), to inform clinical management of...
PURPOSE
To determine the correlation between HPV (human papillomavirus) 52 viral load, multiple infections and ThinPrep cytology test (TCT), to inform clinical management of HPV52-positive women after cervical cancer screening.
METHODS
A total of 1,882 female patients who had positive quantitative HPV tests at Yuebei People's Hospital from January 2020 to December 2022, of whom 533 tested positive for HPV52. We excluded patients who combined HPV16 and/or HPV 18 positivity and whom HPV52 viral load could not be calculated. The final enrollment was 488 patients, including 400 NILM, 48 ASC-US, 28 LSIL and 12 HSIL. The HPV test is a quantitative multiplexed fluorescent PCR assay that provides both HPV genotyping and viral load.
RESULTS
In our study, there were differences in the median distribution of viral loads among various cytological class categories. The risk of TCT results (LSIL or worse) was increased with the increase of HPV52 viral load, for every LOG unit increase in HPV52 viral load, the risk increased by 26.6%. More importantly, we found a nonlinear relationship between HPV52 viral load and TCT results (LSIL or worse) in both single and multiple infections. When the viral load reaches a threshold, the risk of abnormal cytological results increases significantly.
CONCLUSION
HPV52 viral load is an independent risk factor for TCT results (LSIL or worse). The relationship between HPV52 viral load and TCT results (LSIL or worse) is not linear. Viral load may be used as a triage indicator for HPV52-positive patients, thus improving the post-screening clinical management of HPV52-positive women.
Topics: Adult; Aged; Female; Humans; Middle Aged; Young Adult; Coinfection; DNA, Viral; Early Detection of Cancer; Genotype; Human Papillomavirus Viruses; Papillomavirus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears; Viral Load
PubMed: 38654353
DOI: 10.1186/s12985-024-02356-4 -
Annals of Neurology Oct 2023Here, we provide the first regional analysis of intact and defective HIV reservoirs within the brain. Brain tissue from both viremic and virally suppressed people with...
Here, we provide the first regional analysis of intact and defective HIV reservoirs within the brain. Brain tissue from both viremic and virally suppressed people with HIV (PWH) harbored HIV pol DNA in all regions tested, with lower levels present in basal ganglia and cerebellum relative to frontal white matter. Intact proviruses were primarily found in the frontal white matter but also detected in other brain regions of PWH, demonstrating frontal white matter as a major brain reservoir of intact, potentially replication competent HIV DNA that persists despite antiretroviral therapy. ANN NEUROL 2023;94:798-802.
Topics: Humans; Proviruses; CD4-Positive T-Lymphocytes; HIV-1; Viral Load; HIV Infections; Brain
PubMed: 37493435
DOI: 10.1002/ana.26750 -
Cell Host & Microbe Apr 2024Human cytomegalovirus (HCMV) is an important human pathogen that regulates host immunity and hijacks host compartments, including lysosomes, to assemble virions. We...
Human cytomegalovirus (HCMV) is an important human pathogen that regulates host immunity and hijacks host compartments, including lysosomes, to assemble virions. We combined a quantitative proteomic analysis of HCMV infection with a database of proteins involved in vacuolar acidification, revealing Dmx-like protein-1 (DMXL1) as the only protein that acidifies vacuoles yet is degraded by HCMV. Systematic comparison of viral deletion mutants reveals the uncharacterized 7 kDa US33A protein as necessary and sufficient for DMXL1 degradation, which occurs via recruitment of the E3 ubiquitin ligase Kip1 ubiquitination-promoting complex (KPC). US33A-mediated DMXL1 degradation inhibits lysosome acidification and autophagic cargo degradation. Formation of the virion assembly compartment, which requires lysosomes, occurs significantly later with US33A-expressing virus infection, with reduced viral replication. These data thus identify a viral strategy for cellular remodeling, with the potential to employ US33A in therapies for viral infection or rheumatic conditions, in which inhibition of lysosome acidification can attenuate disease.
Topics: Humans; Cytomegalovirus; Proteomics; Virus Assembly; Virus Replication; Proteins; Autophagy; Lysosomes; Hydrogen-Ion Concentration
PubMed: 38479395
DOI: 10.1016/j.chom.2024.02.013 -
Viruses May 2024Duck Tembusu Virus (DTMUV) is a pathogen of the Flaviviridae family that causes infections in poultry, leading to significant economic losses in the duck farming... (Review)
Review
Duck Tembusu Virus (DTMUV) is a pathogen of the Flaviviridae family that causes infections in poultry, leading to significant economic losses in the duck farming industry in recent years. Ducks infected with this virus exhibit clinical symptoms such as decreased egg production and neurological disorders, along with serious consequences such as ovarian hemorrhage, organ enlargement, and necrosis. Variations in morbidity and mortality rates exist across different age groups of ducks. It is worth noting that DTMUV is not limited to ducks alone; it can also spread to other poultry such as chickens and geese, and antibodies related to DTMUV have even been found in duck farm workers, suggesting a potential risk of zoonotic transmission. This article provides a detailed overview of DTMUV research, delving into its genomic characteristics, vaccines, and the interplay with host immune responses. These in-depth research findings contribute to a more comprehensive understanding of the virus's transmission mechanism and pathogenic process, offering crucial scientific support for epidemic prevention and control.
Topics: Animals; Ducks; Flavivirus; Flavivirus Infections; Genome, Viral; Poultry Diseases; Viral Vaccines; Farmers; Antibodies, Viral; Humans
PubMed: 38793692
DOI: 10.3390/v16050811