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Emerging Microbes & Infections Jun 2024
PubMed: 38922308
DOI: 10.1080/22221751.2024.2373309 -
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 -
International Journal of Molecular... May 2024The proteasome generates the majority of peptides presented on MHC class I molecules. The cleavage pattern of the proteasome has been shown to be changed via the...
The proteasome generates the majority of peptides presented on MHC class I molecules. The cleavage pattern of the proteasome has been shown to be changed via the proteasome activator (PA)28 alpha beta (PA28αβ). In particular, several immunogenic peptides have been reported to be PA28αβ-dependent. In contrast, we did not observe a major impact of PA28αβ on the generation of different major histocompatibility complex (MHC) classI ligands. PA28αβ-knockout mice infected with the () or virus showed a normal cluster of differentiation (CD) 8 response and viral clearance. However, we observed that the adoptive transfer of wild-type cells into PA28αβ-knockout mice led to graft rejection, but not vice versa. Depletion experiments showed that the observed rejection was mediated by CD8 cytotoxic T cells. These data indicate that PA28αβ might be involved in the development of the CD8 T cell repertoire in the thymus. Taken together, our data suggest that PA28αβ is a crucial factor determining T cell selection and, therefore, impacts graft acceptance.
Topics: Animals; Graft Rejection; Mice; CD8-Positive T-Lymphocytes; Histocompatibility Antigens Class I; Mice, Knockout; Proteasome Endopeptidase Complex; Ligands; Mice, Inbred C57BL; Lymphocytic choriomeningitis virus; Vaccinia virus
PubMed: 38891837
DOI: 10.3390/ijms25115649 -
Journal of Medical Virology Jun 2024Human immunodeficiency virus (HIV) infection is still a global public health issue, and the development of an effective prophylactic vaccine inducing potent neutralizing...
Human immunodeficiency virus (HIV) infection is still a global public health issue, and the development of an effective prophylactic vaccine inducing potent neutralizing antibodies remains a significant challenge. This study aims to explore the inflammation-related proteins associated with the neutralizing antibodies induced by the DNA/rTV vaccine. In this study, we employed the Olink chip to analyze the inflammation-related proteins in plasma in healthy individuals receiving HIV candidate vaccine (DNA priming and recombinant vaccinia virus rTV boosting) and compared the differences between neutralizing antibody-positive (nab + ) and -negative(nab-) groups. We identified 25 differentially expressed factors and conducted enrichment and correlation analysis on them. Our results revealed that significant expression differences in artemin (ARTN) and C-C motif chemokine ligand 23 (CCL23) between nab+ and -nab- groups. Notably, the expression of CCL23 was negatively corelated to the ID of neutralizing antibodies and the intensity of the CD4 T cell responses. This study enriches our understanding of the immune picture induced by the DNA/rTV vaccine, and provides insights for future HIV vaccine development.
Topics: Humans; Antibodies, Neutralizing; Vaccinia virus; HIV Antibodies; HIV-1; Adult; Proteomics; AIDS Vaccines; Male; HIV Infections; Vaccines, DNA; Female; Healthy Volunteers; Vaccines, Synthetic; Plasma; Young Adult
PubMed: 38888113
DOI: 10.1002/jmv.29749 -
Nature Communications Jun 2024Virus infectivity is traditionally determined by endpoint titration in cell cultures, and requires complex processing steps and human annotation. Here we developed an...
Virus infectivity is traditionally determined by endpoint titration in cell cultures, and requires complex processing steps and human annotation. Here we developed an artificial intelligence (AI)-powered automated framework for ready detection of virus-induced cytopathic effect (DVICE). DVICE uses the convolutional neural network EfficientNet-B0 and transmitted light microscopy images of infected cell cultures, including coronavirus, influenza virus, rhinovirus, herpes simplex virus, vaccinia virus, and adenovirus. DVICE robustly measures virus-induced cytopathic effects (CPE), as shown by class activation mapping. Leave-one-out cross-validation in different cell types demonstrates high accuracy for different viruses, including SARS-CoV-2 in human saliva. Strikingly, DVICE exhibits virus class specificity, as shown with adenovirus, herpesvirus, rhinovirus, vaccinia virus, and SARS-CoV-2. In sum, DVICE provides unbiased infectivity scores of infectious agents causing CPE, and can be adapted to laboratory diagnostics, drug screening, serum neutralization or clinical samples.
Topics: Humans; Artificial Intelligence; Cytopathogenic Effect, Viral; SARS-CoV-2; Microscopy; COVID-19; Neural Networks, Computer; Animals; Vaccinia virus; Saliva; Chlorocebus aethiops; Vero Cells; Rhinovirus; Cell Line
PubMed: 38879641
DOI: 10.1038/s41467-024-49444-1 -
International Journal of Infectious... Jun 2024Monkeypox (Mpox) is a neglected viral endemic tropical disease in both Central and Western African countries transmitted to humans by an animal. However, the natural...
Monkeypox (Mpox) is a neglected viral endemic tropical disease in both Central and Western African countries transmitted to humans by an animal. However, the natural reservoir of the virus remains elusive. In this study we looked for potential reservoirs of MPXV in Gabonese wildlife to prevent future outbreaks and enrich the literature with additional data on animal reservoirs. DNA was extracted from livers and spleens from 2549 animals (bats (859), bushmeats (356), rodents (1309), and shrews (25)) collected between 2012 and 2021. DNA was analyzed by real-time and conventional PCR targeting the 14 KD Protein and the rpo subunit RNA polymerase of orthopoxviruses. No MPXV DNA was detected despite the presence of potential host reservoirs like Critcetomys, Crocidura, Praomys, and Atherurus africanus. This absence could be due to: (i) the low number of animals collected for some species, (ii) the acute nature of Mpox infection, but also (iii) the lack of the potential reservoir Funisciurus anerythrus among collected animals, and (iv) the fact that the samplings are not included in the probable ecological niche of MPXV. Longitudinal studies including potential ecological niches of both F. anerythrus and MPXV in Gabon may be useful to get more information on MPXV circulation.
PubMed: 38878993
DOI: 10.1016/j.ijid.2024.107106 -
Cornea Jun 2024The objective of this study was to present a rare case of prolonged and severe ocular monkeypox virus infection in the absence of systemic manifestations.
PURPOSE
The objective of this study was to present a rare case of prolonged and severe ocular monkeypox virus infection in the absence of systemic manifestations.
METHODS
This was a single case report.
RESULTS
A 60-year-old man, having been symptomatic for 9 days, presented with several umbilicated, ulcerated papules on the left cheek, left side of the nose, and left upper eyelid, along with marked follicular conjunctivitis and multiple conjunctival ulcerations. Two weeks after presentation, he developed an irregular, 360° circumferential opacity in the peripheral cornea that progressed to a large epithelial defect with corneal thinning. Although the initial eyelid lesions and conjunctivitis quickly resolved, the patient experienced nonresolving corneal inflammation manifest with peripheral corneal thinning, epithelial defects, and stromal keratitis. Four months after presentation, with the presumptive diagnosis of peripheral ulcerative keratitis, the patient was treated with intravenous steroids and immunosuppressive treatment, after which the ocular surface inflammation improved. However, the inflammation recurred 12 weeks later, and the patient developed severe perilimbal necrotizing conjunctivitis, followed by recurrence of ulcerated nodular eyelid lesions. Eight months after presentation, nucleic acid amplification tests from eyelid lesion swabs returned positive for nonvariola Orthopoxviruses, which led to the diagnosis of mpox. Within 2 weeks of beginning antiviral treatment with systemic tecovirimat and cidofovir and topical trifluridine, the eyelid lesions, conjunctivitis, and corneal inflammation resolved.
CONCLUSIONS
We present an unusual and challenging case of ocular mpox with severe ocular surface inflammation including peripheral corneal thinning and epithelial defects, without systemic disease. Initiation of antiviral treatment resulted in a quick resolution of the ocular disease.
PubMed: 38870146
DOI: 10.1097/ICO.0000000000003574 -
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 -
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