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JMIR Public Health and Surveillance Mar 2024The worldwide human monkeypox (mpox) outbreak in 2022 mainly affected men who have sex with men (MSM). In China, young men who have sex with men (YMSM) were at a...
Behavioral Intention of Receiving Monkeypox Vaccination and Undergoing Monkeypox Testing and the Associated Factors Among Young Men Who Have Sex With Men in China: Large Cross-Sectional Study.
BACKGROUND
The worldwide human monkeypox (mpox) outbreak in 2022 mainly affected men who have sex with men (MSM). In China, young men who have sex with men (YMSM) were at a potential high risk of mpox infection due to their sexual activeness and the eased COVID-19 restrictions at the end of 2022.
OBJECTIVE
This study aimed to investigate the behavioral intention of receiving mpox vaccination and undergoing mpox testing in 4 different scenarios and explore their associations with background and behavioral theory-related factors among Chinese YMSM.
METHODS
An online cross-sectional survey was conducted among YMSM aged 18-29 years from 6 representative provinces of China in September 2022. Participants recruited (recruitment rate=2918/4342, 67.2%) were asked to self-administer an anonymous questionnaire designed based on prior knowledge about mpox and classic health behavior theories. Data on the participants' background, mpox knowledge and cognition, mpox vaccination and testing cognition, and the behavioral intention of receiving mpox vaccination and undergoing mpox testing were collected. Descriptive analysis and univariate and multivariate linear regressions were performed. Geodetector was used to measure the stratified heterogeneity of behavioral intention.
RESULTS
A total of 2493 YMSM with a mean age of 24.6 (SD 2.9) years were included. The prevalence of having a behavioral intention of receiving mpox vaccination ranged from 66.2% to 88.4% by scenario, varying in epidemic status and cost. The prevalence of having an mpox testing intention was above 90% in all scenarios regardless of the presence of symptoms and the cost. The positive factors related to vaccination intention included mpox knowledge (b=0.060, 95% CI 0.016-0.103), perceived susceptibility of mpox (b=0.091, 95% CI 0.035-0.146), perceived severity of mpox (b=0.230, 95% CI 0.164-0.296), emotional distress caused by mpox (b=0.270, 95% CI 0.160-0.380), perceived benefits of mpox vaccination (b=0.455, 95% CI 0.411-0.498), self-efficacy of mpox vaccination (b=0.586, 95% CI 0.504-0.668), and having 1 male sex partner (b=0.452, 95% CI 0.098-0.806), while the negative factor was perceived barriers to vaccination (b=-0.056, 95% CI -0.090 to -0.022). The positive factors related to testing intention were perceived severity of mpox (b=0.283, 95% CI 0.241-0.325), perceived benefits of mpox testing (b=0.679, 95% CI 0.636-0.721), self-efficacy of mpox testing (b=0.195, 95% CI 0.146-0.245), having 1 male sex partner (b=0.290, 95% CI 0.070-0.510), and having in-person gatherings with MSM (b=0.219, 95% CI 0.072-0.366), while the negative factor was emotional distress caused by mpox (b=-0.069, 95% CI -0.137 to -0.001).
CONCLUSIONS
Among Chinese YMSM, the intention of undergoing mpox testing is optimal, while the mpox vaccination intention has room for improvement. A future national response should raise YMSM's mpox knowledge, disseminate updated information about mpox and preventive measures, improve preventive service accessibility and privacy, and provide advice on positively coping with the associated emotional distress.
Topics: Male; Humans; Young Adult; Adult; Homosexuality, Male; Cross-Sectional Studies; Smallpox Vaccine; Intention; Mpox (monkeypox); Sexual and Gender Minorities; China; Clinical Laboratory Techniques
PubMed: 38502181
DOI: 10.2196/47165 -
Frontiers in Cellular and Infection... 2024Monkeypox (now Mpox), a zoonotic disease caused by the monkeypox virus (MPXV) is an emerging threat to global health. In the time span of only six months, from May to...
Monkeypox (now Mpox), a zoonotic disease caused by the monkeypox virus (MPXV) is an emerging threat to global health. In the time span of only six months, from May to October 2022, the number of MPXV cases breached 80,000 and many of the outbreaks occurred in locations that had never previously reported MPXV. Currently there are no FDA-approved MPXV-specific vaccines or treatments, therefore, finding drugs to combat MPXV is of utmost importance. The A42R profilin-like protein of the MPXV is involved in cell development and motility making it a critical drug target. A42R protein is highly conserved across orthopoxviruses, thus A42R inhibitors may work for other family members. This study sought to identify potential A42R inhibitors for MPXV treatment using computational approaches. The energy minimized 3D structure of the A42R profilin-like protein (PDB ID: 4QWO) underwent virtual screening using a library of 36,366 compounds from Traditional Chinese Medicine (TCM), AfroDb, and PubChem databases as well as known inhibitor tecovirimat via AutoDock Vina. A total of seven compounds comprising PubChem CID: 11371962, ZINC000000899909, ZINC000001632866, ZINC000015151344, ZINC000013378519, ZINC000000086470, and ZINC000095486204, predicted to have favorable binding were shortlisted. Molecular docking suggested that all seven proposed compounds have higher binding affinities to A42R (-7.2 to -8.3 kcal/mol) than tecovirimat (-6.7 kcal/mol). This was corroborated by MM/PBSA calculations, with tecovirimat demonstrating the highest binding free energy of -68.694 kJ/mol (lowest binding affinity) compared to the seven shortlisted compounds that ranged from -73.252 to -97.140 kJ/mol. Furthermore, the 7 compounds in complex with A42R demonstrated higher stability than the A42R-tecovirimat complex when subjected to 100 ns molecular dynamics simulations. The protein-ligand interaction maps generated using LigPlot+ suggested that residues Met1, Glu3, Trp4, Ile7, Arg127, Val128, Thr131, and Asn133 are important for binding. These seven compounds were adequately profiled to be potential antivirals via PASS predictions and structural similarity searches. All seven potential lead compounds were scored Pa > Pi for antiviral activity while ZINC000001632866 and ZINC000015151344 were predicted as poxvirus inhibitors with Pa values of 0.315 and 0.215, and Pi values of 0.052 and 0.136, respectively. Further experimental validations of the identified lead compounds are required to corroborate their predicted activity. These seven identified compounds represent solid footing for development of antivirals against MPXV and other orthopoxviruses.
Topics: Profilins; Monkeypox virus; Molecular Docking Simulation; Benzamides; Antiviral Agents
PubMed: 38500508
DOI: 10.3389/fcimb.2024.1351737 -
PloS One 2024Ionizing radiation (IR) and oncolytic viruses are both used to treat cancer, and the effectiveness of both agents depends upon stimulating an immune response against the...
Ionizing radiation (IR) and oncolytic viruses are both used to treat cancer, and the effectiveness of both agents depends upon stimulating an immune response against the tumor. In this study we tested whether combining image guided ionizing radiation (IG-IR) with an oncolytic vaccinia virus (VACV) could yield a better therapeutic response than either treatment alone. ΔF4LΔJ2R VACV grew well on irradiated human and mouse breast cancer cells, and the virus can be combined with 4 or 8 Gy of IR to kill cells in an additive or weakly synergistic manner. To test efficacy in vivo we used immune competent mice bearing orthotopic TUBO mammary tumors. IG-IR worked well with 10 Gy producing 80% complete responses, but this was halved when the tumors were treated with VACV starting 2 days after IG-IR. VACV monotherapy was ineffective in this model. The antagonism was time dependent as waiting for 21 days after IG-IR eliminated the inhibitory effect but without yielding any further benefits over IR alone. In irradiated tumors, VACV replication was also lower, suggesting that irradiation created an environment that did not support infection as well in vivo as in vitro. A study of how four different treatment regimens affected the immune composition of the tumor microenvironment showed that treating irradiated tumors with VACV altered the immunological profiles in tumors exposed to IR or VACV alone. We detected more PD-1 and PD-L1 expression in tumors exposed to IR+VACV but adding an αPD-1 antibody to the protocol did not change the way VACV interferes with IG-IR therapy. VACV encodes many immunosuppressive gene products that may interfere with the ability of radiotherapy to induce an effective anti-tumor immune response through the release of danger-associated molecular patterns. These data suggest that infecting irradiated tumors with VACV, too soon after exposure, may interfere in the innate and linked adaptive immune responses that are triggered by radiotherapy to achieve a beneficial impact.
Topics: Humans; Animals; Mice; Vaccinia virus; Oncolytic Viruses; Radiotherapy, Image-Guided; Vaccinia; Mammary Neoplasms, Animal; Immunotherapy; Oncolytic Virotherapy; Tumor Microenvironment
PubMed: 38498459
DOI: 10.1371/journal.pone.0298437 -
Emerging Microbes & Infections Dec 2024Generating an infectious non-human primate (NHP) model using a prevalent monkeypox virus (MPXV) strain has emerged as a crucial strategy for assessing the efficacy of...
Generating an infectious non-human primate (NHP) model using a prevalent monkeypox virus (MPXV) strain has emerged as a crucial strategy for assessing the efficacy of vaccines and antiviral drugs against human MPXV infection. Here, we established an animal model by infecting cynomolgus macaques with the prevalent MPXV strain, WIBP-MPXV-001, and simulating its natural routes of infection. A comprehensive analysis and evaluation were conducted on three animals, including monitoring clinical symptoms, collecting hematology data, measuring viral loads, evaluating cellular and humoral immune responses, and examining histopathology. Our findings revealed that initial skin lesions appeared at the inoculation sites and subsequently spread to the limbs and back, and all infected animals exhibited bilateral inguinal lymphadenopathy, eventually leading to a self-limiting disease course. Viral DNA was detected in post-infection blood, nasal, throat, rectal and blister fluid swabs. These observations indicate that the NHP model accurately reflects critical clinical features observed in human MPXV infection. Notably, the animals displayed clinical symptoms and disease progression similar to those of humans, rather than a lethal outcome as observed in previous studies. Historically, MPXV was utilized as a surrogate model for smallpox. However, our study contributes to a better understanding of the dynamics of current MPXV infections while providing a potential infectious NHP model for further evaluation of vaccines and antiviral drugs against mpox infection. Furthermore, the challenge model closely mimics the primary natural routes of transmission for human MPXV infections. This approach enhances our understanding of the precise mechanisms underlying the interhuman transmission of MPXV.
Topics: Animals; Humans; Monkeypox virus; Mpox (monkeypox); Vaccines; Antiviral Agents; Macaca
PubMed: 38494777
DOI: 10.1080/22221751.2024.2332669 -
Euro Surveillance : Bulletin Europeen... Mar 2024Since the beginning of 2023, the number of people with suspected monkeypox virus (MPXV) infection have sharply increased in the Democratic Republic of the Congo (DRC)....
Since the beginning of 2023, the number of people with suspected monkeypox virus (MPXV) infection have sharply increased in the Democratic Republic of the Congo (DRC). We report near-to-complete MPXV genome sequences derived from six cases from the South Kivu province. Phylogenetic analyses reveal that the MPXV affecting the cases belongs to a novel Clade I sub-lineage. The outbreak strain genome lacks the target sequence of the probe and primers of a commonly used Clade I-specific real-time PCR.
Topics: Humans; Monkeypox virus; Mpox (monkeypox); Democratic Republic of the Congo; Phylogeny; Disease Outbreaks
PubMed: 38487886
DOI: 10.2807/1560-7917.ES.2024.29.11.2400106 -
Medical Hypothesis, Discovery &... 2023
PubMed: 38476572
DOI: 10.51329/mehdiophthal1481 -
Cell Reports Mar 2024Histone deacetylases (HDACs) regulate gene expression and innate immunity. Previously, we showed that HDAC5 is degraded during Vaccinia virus (VACV) infection and is a...
Histone deacetylases (HDACs) regulate gene expression and innate immunity. Previously, we showed that HDAC5 is degraded during Vaccinia virus (VACV) infection and is a restriction factor for VACV and herpes simplex virus type 1. Here, we report that HDAC5 promotes interferon regulatory factor 3 (IRF3) activation downstream of Toll-IL-1 receptor (TIR) domain-containing adaptor molecule-1 or Sendai virus-mediated stimulation without requiring HDAC activity. Loss of HDAC5-mediated IRF3 activation is restored by re-introduction of HDAC5 but not HDAC1 or HDAC4. The antiviral activity of HDAC5 is antagonized by VACV protein C6 and orthologs from the orthopoxviruses cowpox, rabbitpox, camelpox, monkeypox, and variola. Infection by many of these viruses induces proteasomal degradation of HDAC5, and expression of C6 alone can induce HDAC5 degradation. Mechanistically, C6 binds to the dimerization domain of HDAC5 and prevents homodimerization and heterodimerization with HDAC4. Overall, this study describes HDAC5 as a positive regulator of IRF3 activation and provides mechanistic insight into how the poxviral protein C6 binds to HDAC5 to antagonize its function.
Topics: Monkeypox virus; Variola virus; Orthopoxvirus; Interferon Regulatory Factor-3; Vaccinia virus; Histone Deacetylases
PubMed: 38461415
DOI: 10.1016/j.celrep.2024.113788 -
Journal For Immunotherapy of Cancer Mar 2024The redundant extracellular matrix (ECM) within tumor microenvironment (TME) such as hyaluronic acid (HA) often impairs intratumoral dissemination of antitumor drugs....
BACKGROUND
The redundant extracellular matrix (ECM) within tumor microenvironment (TME) such as hyaluronic acid (HA) often impairs intratumoral dissemination of antitumor drugs. Oncolytic viruses (OVs) are being studied extensively for cancer therapy either alone or in conjunction with chemotherapy and immunotherapy. Here, we designed a novel recombinant vaccinia virus encoding a soluble version of hyaluronidase Hyal1 (OVV-Hyal1) to degrade the HA and investigated its antitumor effects in combination with chemo drugs, polypeptide, immune cells, and antibodies.
METHODS
We constructed a recombinant oncolytic vaccinia virus encoding the hyaluronidase, and investigated its function in remodeling the ECM of the TME, the antitumor efficacy both in vitro and in several murine solid tumors either alone, or in combination with chemo drugs including doxorubicin and gemcitabine, with polypeptide liraglutide, with immune therapeutics such as PD-L1/PD-1 blockade, CD47 antibody, and with CAR-T cells.
RESULTS
Compared with control OVV, intratumoral injection of OVV-Hyal1 showed superior antitumor efficacies in a series of mouse subcutaneous tumor models. Moreover, HA degradation by OVV-Hyal1 resulted in increased intratumoral dissemination of chemo drugs, infiltration of T cells, NK cells, macrophages, and activation of CD8 T cells. When OVV-Hyal1 was combined with some antitumor therapeutics, for example, doxorubicin, gemcitabine, liraglutide, anti-PD-1, anti-CD47 blockade, or CAR-T cells, more profound therapeutic outcomes were obtained.
CONCLUSIONS
OVV-Hyal1 effectively degrades HA to reshape the TME, therefore overcoming some major hurdles in current cancer therapy, such as limited OVs spread, unfavored dissemination of chemo drugs, polypeptides, antibodies, and insufficient infiltration of effector immune cells. OVV-Hyal1 holds the promise to improve the antitumor outcomes of current cancer therapeutics.
Topics: Mice; Animals; Oncolytic Viruses; Vaccinia virus; Hyaluronoglucosaminidase; Oncolytic Virotherapy; Gemcitabine; CD8-Positive T-Lymphocytes; Liraglutide; Neoplasms; Immunotherapy; Disease Models, Animal; Peptides; Extracellular Matrix; Doxorubicin; Tumor Microenvironment
PubMed: 38458640
DOI: 10.1136/jitc-2023-008431 -
Cell Reports Mar 2024Numerous viruses alter host microtubule (MT) networks during infection, but how and why they induce these changes is unclear in many cases. We show that the vaccinia...
Numerous viruses alter host microtubule (MT) networks during infection, but how and why they induce these changes is unclear in many cases. We show that the vaccinia virus (VV)-encoded A51R protein is a MT-associated protein (MAP) that directly binds MTs and stabilizes them by both promoting their growth and preventing their depolymerization. Furthermore, we demonstrate that A51R-MT interactions are conserved across A51R proteins from multiple poxvirus genera, and highly conserved, positively charged residues in A51R proteins mediate these interactions. Strikingly, we find that viruses encoding MT interaction-deficient A51R proteins fail to suppress a reactive oxygen species (ROS)-dependent antiviral response in macrophages that leads to a block in virion morphogenesis. Moreover, A51R-MT interactions are required for VV virulence in mice. Collectively, our data show that poxviral MAP-MT interactions overcome a cell-intrinsic antiviral ROS response in macrophages that would otherwise block virus morphogenesis and replication in animals.
Topics: Animals; Mice; Reactive Oxygen Species; Virus Replication; Poxviridae; Vaccinia virus; Viral Proteins; Microtubules; Antiviral Agents
PubMed: 38457341
DOI: 10.1016/j.celrep.2024.113882 -
Narra J Apr 2023The recent spread of the monkeypox virus (MPXV), causing monkeypox (mpox), to non-endemic areas, and the atypical and unusual clinical manifestations observed during its... (Review)
Review
The recent spread of the monkeypox virus (MPXV), causing monkeypox (mpox), to non-endemic areas, and the atypical and unusual clinical manifestations observed during its 2022 outbreak has focused international interest on the clinical features of the disease. Mpox is usually a self-limiting disease with mild symptoms with common manifestations, including fever and skin lesions; however, severe manifestations could occur in some vulnerable groups (children and those with impaired immune systems) and may present multisystem complications and fatal outcomes. In most cases, a fever is the first sign of disease, followed by the development of various inflammatory lesions on the skin, such as vesiculopustular rashes and ulcers. Pneumonitis, encephalitis, keratitis, secondary bacterial infections, acute kidney injury, and myocarditis are all possible outcomes of the infection. Myocarditis has been reported to be caused by orthopoxviruses, and it is a serious condition of which its pathophysiology is little understood. Recent reports have indicated myocarditis with cardiac involvement as a possible atypical and unusual consequence of the MPXV infection during present outbreak. This review provides an overview of the clinical manifestations of mpox with a special focus on its effects on the heart, including myocarditis. The evidence of the myocarditis in mpox patients and its possible pathogenesis are discussed.
PubMed: 38450040
DOI: 10.52225/narra.v3i1.104