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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 -
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 -
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 -
The Lancet. Microbe Jun 2024Since the emergence of the global mpox outbreak in May, 2022, more than 90 000 cases have been diagnosed across 110 countries, disproportionately affecting people with...
BACKGROUND
Since the emergence of the global mpox outbreak in May, 2022, more than 90 000 cases have been diagnosed across 110 countries, disproportionately affecting people with HIV. The durability of mpox-specific immunity is unclear and reinfections have been reported. We aimed to compare mpox immune responses up to 6 months after diagnosis in participants with and without HIV and assess their effect on disease severity and viral clearance dynamics.
METHODS
This study was embedded within a prospective, observational, multicentre cohort study of viral clearance dynamics among people with mpox in Spain (MoViE). We included women and men aged 18 years or older, who had signs of mpox, and reported having symptom onset within the previous 10 days at the moment of mpox diagnosis from three sex clinics of the Barcelona metropolitan area. Samples from skin ulcers were collected weekly to estimate the time to clear monkeypox virus (MPXV) from skin lesions. Blood samples were taken at diagnosis, 29, 91, and 182 days later for immune analysis. This included quantifying IgG and IgA against three mpox antigens by ELISA, evaluating in-vitro neutralisation, and characterising mpox-specific T-cell responses using interferon γ detecting enzyme-linked immunospot (ELISpot) assay and multiparametric flow cytometry.
FINDINGS
Of the 77 originally enrolled participants, we included 33 participants recruited between July 19, and Oct 6, 2022. Participants without HIV (19 [58%] participants) and participants with HIV (14 [42%] participants) had similar clinical severity and time to MPXV clearance in skin lesions. Participants with HIV had a CD4 T-cell count median of 777 cells per μL (IQR 484-1533), and 11 (78%) of 14 were virally suppressed on antiretroviral therapy. Nine (27%) of 33 participants were age 49 years or older. 15 (45%) of 33 participants were originally from Spain, and all participants were men. Early humoral responses, particularly concentrations and breadth of IgG and IgA, were associated with milder disease and faster viral clearance. Orthopoxvirus-specific T cells count was also positively correlated with MPXV clearance. Antibody titres declined more rapidly in participants with HIV, but T-cell responses against MPXV were sustained up to day 182 after diagnosis, regardless of HIV status.
INTERPRETATION
Higher breadth and magnitude of B-cell and T-cell responses are important in facilitating local viral clearance, limiting mpox dissemination, and reducing disease severity in individuals with preserved immune system. Antibodies appear to contribute to early viral control and T-cell responses are sustained over time, which might contribute to milder presentations during reinfection.
FUNDING
Fundació Lluita contra les Infeccions, IrsiCaixa, and Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación e Universidades.
PubMed: 38857615
DOI: 10.1016/S2666-5247(24)00074-0 -
F1000Research 2023A zoonotic, double-stranded DNA virus belonging to the genus Orthopoxvirus, the mpox virus (MPXV) is most common in tropical regions of Central and West Africa. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A zoonotic, double-stranded DNA virus belonging to the genus Orthopoxvirus, the mpox virus (MPXV) is most common in tropical regions of Central and West Africa. The frequency of monkeypox (mpox) cases, however, has sharply climbed globally since May 2022.
OBJECTIVES
To establish the threat of mpox in terms of the oral lesions caused in sufferers.
MATERIALS AND METHODS
After a thorough study of the literature identified in the PubMed, Web of Science, and Cochrane library databases using the PRISMA framework, 103 papers were found. Using inclusion and exclusion criteria, we chose research that was relevant for our review before shortlisting 14 papers that conformed to the review's guidelines.
RESULTS
In the 14 selected studies, it was found that oral lesions were among the first clinical signs of a mpox affliction, with ulcers on the dorsal surface of tongue lips being the most common areas affected.
CONCLUSION
The rarely observed oral lesions of mpox infection may help in the diagnosis and management of this condition. It is critical to keep in mind that recognising and detecting oral lesions in mpox patients opens the door to more research and efficient patient management.
Topics: Mpox (monkeypox); Humans; Monkeypox virus; Animals; Mouth Diseases
PubMed: 38845619
DOI: 10.12688/f1000research.137363.2 -
Veterinary Medicine International 2024This review delves into the historical context, current epidemiological landscape, genomics, and pathobiology of monkeypox virus (MPXV). Furthermore, it elucidates the... (Review)
Review
This review delves into the historical context, current epidemiological landscape, genomics, and pathobiology of monkeypox virus (MPXV). Furthermore, it elucidates the present vaccination status and strategies to curb the spread of monkeypox. Monkeypox, caused by the known as MPXV, is a zoonotic ailment. MPXV can be transmitted from person to person through respiratory droplets during prolonged face-to-face interactions. While many cases of monkeypox are self-limiting, vulnerable groups such as young children, pregnant women, and immunocompromised individuals may experience severe manifestations. Diagnosis predominantly relies on clinical presentations, complemented by laboratory techniques like RT-PCR. Although treatment is often not required, severe cases necessitate antiviral medications like tecovirimat, cidofovir, and brincidofovir. Vaccination, particularly using the smallpox vaccine, has proven instrumental in outbreak control, exhibiting an efficacy of at least 85% against mpox as evidenced by data from Africa. Mitigating transmission requires measures like wearing surgical masks, adequately covering skin lesions, and avoiding handling wild animals.
PubMed: 38836166
DOI: 10.1155/2024/8839830 -
Infectious Medicine Jun 2024In 2022, just before the COVID-19 pandemic ended, many countries noticed a viral monkeypox outbreak. Monkeypox virus, a zoonotic pathogen, causes a febrile illness in... (Review)
Review
In 2022, just before the COVID-19 pandemic ended, many countries noticed a viral monkeypox outbreak. Monkeypox virus, a zoonotic pathogen, causes a febrile illness in humans and resembles smallpox. Prevention strategies encompass vaccination, strict infection control measures, and avoiding contact with infected persons. As monkeypox and related poxviruses continue to pose challenges, ongoing surveillance, early diagnosis, prompt isolation, and effective control measures are crucial for limiting transmission and mitigating the impact of outbreaks on public health. This review provides valuable insights into the evolution of the monkeypox virus and its various modes of transmission, including postmortem transmission, and offers an overall perspective on the guidelines issued by the Government of India to prevent and effectively control the spread of this disease.
PubMed: 38827561
DOI: 10.1016/j.imj.2024.100105 -
Heliyon May 2024Due to the discontinuation of routine smallpox vaccination after its eradication in 1980, a large part of the human population remains naïve against smallpox and other...
Due to the discontinuation of routine smallpox vaccination after its eradication in 1980, a large part of the human population remains naïve against smallpox and other members of the orthopoxvirus genus. As a part of biosafety personnel protection programs, laboratory workers receive prophylactic vaccinations against diverse infectious agents, including smallpox. Here, we studied the levels of cross-protecting neutralizing antibodies as well as total IgG induced by either first- or third-generation smallpox vaccines against Monkeypox virus, using a clinical isolate from the 2022 outbreak. Serum neutralization tests indicated better overall neutralization capacity after vaccination with first-generation smallpox vaccines, compared to an attenuated third-generation vaccine. Results obtained from total IgG ELISA, however, did not show higher induction of orthopoxvirus-specific IgGs in first-generation vaccine recipients. Taken together, our results indicate a lower level of cross-protecting neutralizing antibodies against Monkeypox virus in recipients of third-generation smallpox vaccine compared to first-generation vaccine recipients, although total IgG levels were comparable.
PubMed: 38826712
DOI: 10.1016/j.heliyon.2024.e31490