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Indian Journal of Public Health Oct 2023
Topics: Humans; Disease Outbreaks; Mpox (monkeypox); Climate; India
PubMed: 38934841
DOI: 10.4103/ijph.ijph_1451_22 -
Viruses May 2024Vaccinia virus is the most successful vaccine in human history and functions as a protective vaccine against smallpox and monkeypox, highlighting the importance of... (Review)
Review
Vaccinia virus is the most successful vaccine in human history and functions as a protective vaccine against smallpox and monkeypox, highlighting the importance of ongoing research into vaccinia due to its genetic similarity to other emergent poxviruses. Moreover, vaccinia's ability to accommodate large genetic insertions makes it promising for vaccine development and potential therapeutic applications, such as oncolytic agents. Thus, understanding how superior immunity is generated by vaccinia is crucial for designing other effective and safe vaccine strategies. During vaccinia inoculation by scarification, the skin serves as a primary site for the virus-host interaction, with various cell types playing distinct roles. During this process, hematopoietic cells undergo abortive infections, while non-hematopoietic cells support the full viral life cycle. This differential permissiveness to viral replication influences subsequent innate and adaptive immune responses. Dendritic cells (DCs), key immune sentinels in peripheral tissues such as skin, are pivotal in generating T cell memory during vaccinia immunization. DCs residing in the skin capture viral antigens and migrate to the draining lymph nodes (dLN), where they undergo maturation and present processed antigens to T cells. Notably, CD8+ T cells are particularly significant in viral clearance and the establishment of long-term protective immunity. Here, we will discuss vaccinia virus, its continued relevance to public health, and viral strategies permissive to immune escape. We will also discuss key events and populations leading to long-term protective immunity and remaining key gaps.
Topics: Vaccinia virus; Humans; Immune Evasion; Animals; Vaccinia; Dendritic Cells; Virus Replication; Adaptive Immunity; CD8-Positive T-Lymphocytes
PubMed: 38932162
DOI: 10.3390/v16060870 -
Emerging Microbes & Infections Jun 2024The (OPXV) genus of the includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of...
The (OPXV) genus of the includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of Bcl-2-like proteins of VACV are involved in escaping the host innate immunity. However, little work has been devoted to the evolution and function of their orthologues in other OPXVs. Here, we found that MPXV protein P2, encoded by the gene, and P2 orthologues from other OPXVs, such as VACV protein N2, localize to the nucleus and antagonize interferon (IFN) production. Exceptions to this were the truncated P2 orthologues in camelpox virus (CMLV) and taterapox virus (TATV) that lacked the nuclear localization signal (NLS). Mechanistically, the NLS of MPXV P2 interacted with karyopherin α-2 (KPNA2) to facilitate P2 nuclear translocation, and competitively inhibited KPNA2-mediated IRF3 nuclear translocation and downstream IFN production. Deletion of the NLS in P2 or orthologues significantly enhanced IRF3 nuclear translocation and innate immune responses, thereby reducing viral replication. Moreover, deletion of NLS from N2 in VACV attenuated viral replication and virulence in mice. These data demonstrate that the NLS-mediated translocation of P2 is critical for P2-induced inhibition of innate immunity. Our findings contribute to an in-depth understanding of the mechanisms of OPXV P2 orthologue in innate immune evasion.
PubMed: 38916407
DOI: 10.1080/22221751.2024.2372344 -
Frontiers in Cellular and Infection... 2024While the world struggles to recover from the devastation wrought by the widespread spread of COVID-19, monkeypox virus has emerged as a new global pandemic threat. In...
While the world struggles to recover from the devastation wrought by the widespread spread of COVID-19, monkeypox virus has emerged as a new global pandemic threat. In this paper, a high precision and lightweight classification network MpoxNet based on ConvNext is proposed to meet the need of fast and safe detection of monkeypox classification. In this method, a two-branch depth-separable convolution residual Squeeze and Excitation module is designed. This design aims to extract more feature information with two branches, and greatly reduces the number of parameters in the model by using depth-separable convolution. In addition, our method introduces a convolutional attention module to enhance the extraction of key features within the receptive field. The experimental results show that MpoxNet has achieved remarkable results in monkeypox disease classification, the accuracy rate is 95.28%, the precision rate is 96.40%, the recall rate is 93.00%, and the F1-Score is 95.80%. This is significantly better than the current mainstream classification model. It is worth noting that the FLOPS and the number of parameters of MpoxNet are only 30.68% and 31.87% of those of ConvNext-Tiny, indicating that the model has a small computational burden and model complexity while efficient performance.
Topics: Mpox (monkeypox); Humans; Neural Networks, Computer; COVID-19; Algorithms; SARS-CoV-2; Monkeypox virus; Deep Learning
PubMed: 38912211
DOI: 10.3389/fcimb.2024.1397316 -
MMWR. Morbidity and Mortality Weekly... Jun 2024Tecovirimat is the first-line antiviral treatment recommended for severe mpox or for persons with mpox who are at risk for severe disease; tecovirimat is available in...
Tecovirimat is the first-line antiviral treatment recommended for severe mpox or for persons with mpox who are at risk for severe disease; tecovirimat is available in the United States under an expanded access investigational new drug (IND) protocol. During the 2022-2023 mpox outbreak, local U.S. health jurisdictions facilitated access to tecovirimat. In June 2022, Los Angeles County (LAC) rapidly developed strategies for tecovirimat distribution using existing medical countermeasure distribution networks established by the Public Health Emergency Preparedness Program and the Hospital Preparedness Program, creating a hub and spoke distribution network consisting of 44 hub facilities serving 456 satellite sites across LAC. IND patient intake forms were analyzed to describe mpox patients treated with tecovirimat. Tecovirimat treatment data were matched with case surveillance data to calculate time from specimen collection to patients receiving tecovirimat. Among 2,281 patients with mpox in LAC, 735 (32%) received tecovirimat during June 2022-January 2023. Among treated patients, approximately two thirds (508; 69%) received treatment through community clinics and pharmacies. The median interval from specimen collection to treatment was 2 days (IQR = 0-5 days). Local data collection and analysis helped to minimize gaps in treatment access and facilitated network performance monitoring. During public health emergencies, medical countermeasures can be rapidly deployed across a large jurisdiction using existing distribution networks, including clinics and pharmacies.
Topics: Humans; Disease Outbreaks; Los Angeles; Middle Aged; Adult; Adolescent; Female; Male; Young Adult; Aged; Antiviral Agents; Child; Mpox (monkeypox); Child, Preschool; Infant; Pyrrolidines; Benzamides; Aged, 80 and over; Phthalimides
PubMed: 38900699
DOI: 10.15585/mmwr,mm7324a2 -
Geospatial Health Jun 2024Mpox is an emerging, infectious disease that has caused outbreaks in at least 91 countries from May to August 2022. We assessed the link between international air travel...
Mpox is an emerging, infectious disease that has caused outbreaks in at least 91 countries from May to August 2022. We assessed the link between international air travel patterns and Mpox transmission risk, and the relationship between the translocation of Mpox and human mobility dynamics after travel restrictions due to the COVID-19 pandemic had been lifted. Our three novel observations were that: i) more people traveled internationally after the removal of travel restrictions in the summer of 2022 compared to pre-pandemic levels; ii) countries with a high concentration of global air travel have the most recorded Mpox cases; and iii) Mpox transmission includes a number of previously nonendemic regions. These results suggest that international airports should be a primary location for monitoring the risk of emerging communicable diseases. Findings highlight the need for global collaboration concerning proactive measures emphasizing realtime surveillance.
Topics: Humans; Air Travel; COVID-19; SARS-CoV-2; Mpox (monkeypox); Global Health; Pandemics; Airports; Communicable Diseases, Emerging; Travel; Disease Outbreaks
PubMed: 38872388
DOI: 10.4081/gh.2024.1261 -
Scientific Reports Jun 2024Since spring 2022, the global epidemiology of the monkeypox virus (MPXV) has changed. The unprecedented increase of human clade II MPXV cases worldwide heightened...
Since spring 2022, the global epidemiology of the monkeypox virus (MPXV) has changed. The unprecedented increase of human clade II MPXV cases worldwide heightened concerns about this emerging zoonotic disease. We analysed the positivity rates, viral loads, infectiousness, and persistence of MPXV DNA for up to 4 months in several biological samples from 89 MPXV-confirmed cases. Our data showed that viral loads and positivity rates were higher during the first two weeks of symptoms for all sample types. Amongst no-skin-samples, respiratory specimens showed higher MPXV DNA levels and median time until viral clearance, suggesting their usefulness in supporting MPXV diagnosis, investigating asymptomatic patients, and monitoring viral shedding. Infectious virus was cultured from respiratory samples, semen, and stools, with high viral loads and collected within the first 10 days. Notably, only one saliva and one semen were found positive for viral DNA after 71 and 31 days from symptoms, respectively. The focus on bloodstream samples showed the best testing sensitivity in plasma, reporting the overall highest MPXV DNA detection rate and viral loads during the 3-week follow-up as compared to serum and whole-blood. The data here presented can be useful for MPXV diagnostics and a better understanding of the potential alternative routes of its onward transmission.
Topics: Humans; DNA, Viral; Viral Load; Body Fluids; Male; Monkeypox virus; Kinetics; Semen; Mpox (monkeypox); Saliva; Female; Adult; Virus Shedding; Middle Aged
PubMed: 38866796
DOI: 10.1038/s41598-024-63044-5 -
Journal of Infection and Public Health Jul 2024Poxviruses comprise a group of large double-stranded DNA viruses and are known to cause diseases in humans, livestock animals, and other animal species. The Mpox virus...
Formulation of next-generation polyvalent vaccine candidates against three important poxviruses by targeting DNA-dependent RNA polymerase using an integrated immunoinformatics and molecular modeling approach.
BACKGROUND
Poxviruses comprise a group of large double-stranded DNA viruses and are known to cause diseases in humans, livestock animals, and other animal species. The Mpox virus (MPXV; formerly Monkeypox), variola virus (VARV), and volepox virus (VPXV) are among the prevalent poxviruses of the Orthopoxviridae genera. The ongoing Mpox infectious disease pandemic caused by the Mpox virus has had a major impact on public health across the globe. To date, only limited repurposed antivirals and vaccines are available for the effective treatment of Mpox and other poxviruses that cause contagious diseases.
METHODS
The present study was conducted with the primary goal of formulating multi-epitope vaccines against three evolutionary closed poxviruses i.e., MPXV, VARV, and VPXV using an integrated immunoinformatics and molecular modeling approach. DNA-dependent RNA polymerase (DdRp), a potential vaccine target of poxviruses, has been used to determine immunodominant B and T-cell epitopes followed by interactions analysis with Toll-like receptor 2 at the atomic level.
RESULTS
Three multi-epitope vaccine constructs, namely DdRp_MPXV (V1), DdRp_VARV (V2), and DdRp_VPXV (V3) were designed. These vaccine constructs were found to be antigenic, non-allergenic, non-toxic, and soluble with desired physicochemical properties. Protein-protein docking and interaction profiling analysis depicts a strong binding pattern between the targeted immune receptor TLR2 and the structural models of the designed vaccine constructs, and manifested a number of biochemical bonds (hydrogen bonds, salt bridges, and non-bonded contacts). State-of-the-art all-atoms molecular dynamics simulations revealed highly stable interactions of vaccine constructs with TLR2 at the atomic level throughout the simulations on 300 nanoseconds. Additionally, the outcome of the immune simulation analysis suggested that designed vaccines have the potential to induce protective immunity against targeted poxviruses.
CONCLUSIONS
Taken together, formulated next-generation polyvalent vaccines were found to have good efficacy against closely related poxviruses (MPXV, VARV, and VPXV) as demonstrated by our extensive immunoinformatics and molecular modeling evaluations; however, further experimental investigations are still needed.
Topics: Viral Vaccines; Poxviridae; Computational Biology; Epitopes, T-Lymphocyte; DNA-Directed RNA Polymerases; Models, Molecular; Animals; Humans; Poxviridae Infections; Epitopes, B-Lymphocyte; Molecular Docking Simulation; Immunoinformatics
PubMed: 38865776
DOI: 10.1016/j.jiph.2024.102470 -
Frontiers in Cellular and Infection... 2024Monkeypox (mpox) is an infectious disease caused by the mpox virus and can potentially lead to fatal outcomes. It resembles infections caused by viruses from other... (Review)
Review
Monkeypox (mpox) is an infectious disease caused by the mpox virus and can potentially lead to fatal outcomes. It resembles infections caused by viruses from other families, challenging identification. The pathogenesis, transmission, and clinical manifestations of mpox and other species are similar due to their closely related genetic material. This review provides a comprehensive discussion of the roles of various proteins, including extracellular enveloped virus (EEV), intracellular mature virus (IMV), and profilin-like proteins of mpox. It also highlights recent diagnostic techniques based on these proteins to detect this infection rapidly.
Topics: Monkeypox virus; Humans; Viral Proteins; Mpox (monkeypox); Animals
PubMed: 38863833
DOI: 10.3389/fcimb.2024.1414224 -
Communications Biology Jun 2024The genome folds into complex configurations and structures thought to profoundly impact its function. The intricacies of this dynamic structure-function relationship...
The genome folds into complex configurations and structures thought to profoundly impact its function. The intricacies of this dynamic structure-function relationship are not well understood particularly in the context of viral infection. To unravel this interplay, here we provide a comprehensive investigation of simultaneous host chromatin structural (via Hi-C and ATAC-seq) and functional changes (via RNA-seq) in response to vaccinia virus infection. Over time, infection significantly impacts global and local chromatin structure by increasing long-range intra-chromosomal interactions and B compartmentalization and by decreasing chromatin accessibility and inter-chromosomal interactions. Local accessibility changes are independent of broad-scale chromatin compartment exchange (~12% of the genome), underscoring potential independent mechanisms for global and local chromatin reorganization. While infection structurally condenses the host genome, there is nearly equal bidirectional differential gene expression. Despite global weakening of intra-TAD interactions, functional changes including downregulated immunity genes are associated with alterations in local accessibility and loop domain restructuring. Therefore, chromatin accessibility and local structure profiling provide impactful predictions for host responses and may improve development of efficacious anti-viral counter measures including the optimization of vaccine design.
Topics: Chromatin; Animals; Vaccinia virus; Chlorocebus aethiops; Vero Cells; Vaccinia; Host-Pathogen Interactions; Multiomics
PubMed: 38862613
DOI: 10.1038/s42003-024-06389-x