-
Infection Aug 2023Between May 2022 and January 2023, a global mpox outbreak affected more than 84,000 patients across all continents. Transmission of mpox occurs through large respiratory...
INTRODUCTION
Between May 2022 and January 2023, a global mpox outbreak affected more than 84,000 patients across all continents. Transmission of mpox occurs through large respiratory droplets and direct contact with skin lesions.
CASE PRESENTATION
We present the case of a 31-year-old previously healthy male with mpox-Infection following occupational exposure to mpox from a needle stick injury with a sterile needle through a contaminated glove. The patient presented with a three-day history of fever, malaise, and an increasing erythema and swelling of one fingertip. The patient works as a medical doctor with regular exposure to patients infected with mpox. Mpox-PCR from a swab of the lesion and an oro-pharyngeal swab were positive. The lesion on his finger evolved into a necrotic skin lesion finally healing, leaving a scar. He did not develop any secondary pox on his skin and recovered fully.
DISCUSSION
Only a minority of patients with mpox infection develop illness with pronounced local complications as in this case.
CONCLUSION
Mpox can potentially be transmitted in an occupational context. Medical personnel should be informed about this possible route of transmission.
Topics: Humans; Male; Adult; Mpox (monkeypox); Disease Outbreaks; Skin; Fever; Fingers
PubMed: 36735196
DOI: 10.1007/s15010-023-01989-x -
Cell Reports Aug 2023Viruses acquire host genes via horizontal transfer and can express them to manipulate host biology during infections. Some homologs retain sequence identity, but...
Viruses acquire host genes via horizontal transfer and can express them to manipulate host biology during infections. Some homologs retain sequence identity, but evolutionary divergence can obscure host origins. We use structural modeling to compare vaccinia virus proteins with metazoan proteomes. We identify vaccinia A47L as a homolog of gasdermins, the executioners of pyroptosis. An X-ray crystal structure of A47 confirms this homology, and cell-based assays reveal that A47 interferes with caspase function. We also identify vaccinia C1L as the product of a cryptic gene fusion event coupling a Bcl-2-related fold with a pyrin domain. C1 associates with components of the inflammasome, a cytosolic innate immune sensor involved in pyroptosis, yet paradoxically enhances inflammasome activity, suggesting differential modulation during infections. Our findings demonstrate the increasing power of structural homology screens to reveal proteins with unique combinations of domains that viruses capture from host genes and combine in unique ways.
Topics: Animals; Inflammasomes; Vaccinia; Poxviridae; Vaccinia virus; Viruses
PubMed: 37494187
DOI: 10.1016/j.celrep.2023.112878 -
BMJ Open Gastroenterology Jan 2024Mpox is a viral infection caused by the monkeypox virus, a member of the Poxviridae family and Orthopoxvirus genus. Other well-known viruses of the Orthopoxvirus genus...
INTRODUCTION
Mpox is a viral infection caused by the monkeypox virus, a member of the Poxviridae family and Orthopoxvirus genus. Other well-known viruses of the Orthopoxvirus genus include the variola virus (smallpox), cowpox virus and vaccinia virus. Although there is a plethora of research regarding the dermatological and influenza-like symptoms of mpox, particularly following the 2022 mpox outbreak, more research is needed on the gastrointestinal (GI) effects.
OBJECTIVES
This systematic review is to outline the GI manifestations of the monkeypox virus.
METHODS
The authors conducted this systematic review using guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A search was conducted through the PubMed, EMBASE and MEDLINE databases from January 1958 to June 2023. The authors selected English language papers that discussed the GI symptoms in mpox patients. A manual search was also conducted in the reference sections of these publications for other relevant papers.
RESULTS
33 papers involving 830 patients were selected for this review. The GI manifestations in mpox patients are proctitis, vomiting, diarrhoea, rectal pain, nausea, tenesmus, rectal bleeding and abdominal pain. Although various papers explored transmission routes, one paper established a direct connection between anal-receptive sex transmission route and the development of a GI complication (proctitis). Another study reported that the mode of transmission could potentially impact the occurrence of GI symptoms and severity of the disease. The reviewed papers did not discover a relation between the severity of dermatological and influenza-like symptoms and the GI manifestations mentioned.
CONCLUSION
This systematic review confirms that GI manifestations are observed in mpox patients. GI symptoms of mpox are crucial for gastroenterologists and other healthcare professionals to recognise in order to address patient discomfort and further understand the pathophysiology of the virus.
Topics: Humans; Gastrointestinal Hemorrhage; Mpox (monkeypox); Proctitis; Vomiting
PubMed: 38184298
DOI: 10.1136/bmjgast-2023-001266 -
Journal of Nanobiotechnology Mar 2024The human monkeypox virus (Mpox) is classified as a member of the Poxviridae family and belongs to the Orthopoxvirus genus. Mpox possesses double-stranded DNA, and there... (Review)
Review
The human monkeypox virus (Mpox) is classified as a member of the Poxviridae family and belongs to the Orthopoxvirus genus. Mpox possesses double-stranded DNA, and there are two known genetic clades: those originating in West Africa and the Congo Basin, commonly known as Central African clades. Mpox may be treated with either the vaccinia vaccination or the therapeutics. Modifying the smallpox vaccine for treating and preventing Mpox has shown to be beneficial because of the strong link between smallpox and Mpox viruses and their categorization in the same family. Cross-protection against Mpox is effective with two Food and Drug Administration (FDA)-approved smallpox vaccines (ACAM2000 and JYNNEOSTM). However, ACAM2000 has the potential for significant adverse effects, such as cardiac issues, whereas JYNNEOS has a lower risk profile. Moreover, Mpox has managed to resurface, although with modified characteristics, due to the discontinuation and cessation of the smallpox vaccine for 40 years. The safety and efficacy of the two leading mRNA vaccines against SARS-CoV-2 and its many variants have been shown in clinical trials and subsequent data analysis. This first mRNA treatment model involves injecting patients with messenger RNA to produce target proteins and elicit an immunological response. High potency, the possibility of safe administration, low-cost manufacture, and quick development is just a few of the benefits of RNA-based vaccines that pave the way for a viable alternative to conventional vaccines. When protecting against Mpox infection, mRNA vaccines are pretty efficient and may one day replace the present whole-virus vaccines. Therefore, the purpose of this article is to provide a synopsis of the ongoing research, development, and testing of an mRNA vaccine against Mpox.
Topics: United States; Humans; mRNA Vaccines; Smallpox Vaccine; Smallpox; COVID-19 Vaccines; Mpox (monkeypox); Antigens, Viral
PubMed: 38429829
DOI: 10.1186/s12951-024-02355-1 -
Nature Medicine Sep 2023The 2022 global mpox outbreak raises questions about how this zoonotic disease established effective human-to-human transmission and its potential for further...
The 2022 global mpox outbreak raises questions about how this zoonotic disease established effective human-to-human transmission and its potential for further adaptation. The 2022 outbreak virus is related to an ongoing outbreak in Nigeria originally reported in 2017, but the evolutionary path linking the two remains unclear due to a lack of genomic data between 2018, when virus exportations from Nigeria were first recorded, and 2022, when the global mpox outbreak began. Here, 18 viral genomes obtained from patients across southern Nigeria in 2019-2020 reveal multiple lineages of monkeypox virus (MPXV) co-circulated in humans for several years before 2022, with progressive accumulation of mutations consistent with APOBEC3 activity over time. We identify Nigerian A.2 lineage isolates, confirming the lineage that has been multiply exported to North America independently of the 2022 outbreak originated in Nigeria, and that it has persisted by human-to-human transmission in Nigeria for more than 2 years before its latest exportation. Finally, we identify a lineage-defining APOBEC3-style mutation in all A.2 isolates that disrupts gene A46R, encoding a viral innate immune modulator. Collectively, our data demonstrate MPXV capacity for sustained diversification within humans, including mutations that may be consistent with established mechanisms of poxvirus adaptation.
Topics: Humans; Animals; Monkeypox virus; Mpox (monkeypox); Zoonoses; Disease Outbreaks; Biological Evolution
PubMed: 37710003
DOI: 10.1038/s41591-023-02456-8 -
Nature Communications Dec 2023Modified vaccinia Ankara (MVA) virus does not replicate in human cells and is the vaccine deployed to curb the current outbreak of mpox. Here, we conduct a multiplexed...
Modified vaccinia Ankara (MVA) virus does not replicate in human cells and is the vaccine deployed to curb the current outbreak of mpox. Here, we conduct a multiplexed proteomic analysis to quantify >9000 cellular and ~80% of viral proteins throughout MVA infection of human fibroblasts and macrophages. >690 human proteins are down-regulated >2-fold by MVA, revealing a substantial remodelling of the host proteome. >25% of these MVA targets are not shared with replication-competent vaccinia. Viral intermediate/late gene expression is necessary for MVA antagonism of innate immunity, and suppression of interferon effectors such as ISG20 potentiates virus gene expression. Proteomic changes specific to infection of macrophages indicate modulation of the inflammatory response, including inflammasome activation. Our approach thus provides a global view of the impact of MVA on the human proteome and identifies mechanisms that may underpin its abortive infection. These discoveries will prove vital to design future generations of vaccines.
Topics: Humans; Vaccinia; Proteome; Proteomics; Vaccinia virus; Cell Death; Antiviral Agents
PubMed: 38065956
DOI: 10.1038/s41467-023-43299-8 -
Cureus Aug 2023Monkeypox is a rare zoonotic DNA with lineage from the Poxviridae family, Chordopoxvirinae subfamily, and Orthopoxvirus genus. With a previous history of controlled... (Review)
Review
Monkeypox is a rare zoonotic DNA with lineage from the Poxviridae family, Chordopoxvirinae subfamily, and Orthopoxvirus genus. With a previous history of controlled and contained occasional outbreaks of the virus, currently, a widely erupted outbreak of monkeypox with progressively rising numbers has been reported since May 2022 in multiple countries of the western hemisphere that are not historically endemic for this infection, particularly the United Kingdom and European Union countries. We have written a comprehensive review article to help clinicians better understand the disease. The global cessation of smallpox vaccination has been hypothesized to cause the rise in monkeypox infections in recent years. Monkeypox, like any other viral infection, commences with prodromal symptoms; a maculopapular rash with centrifugal distribution usually follows. Polymerase chain reaction (PCR) confirms the diagnosis. Transmission in humans is possible through infected animals or humans. In the ongoing 2022 outbreak, the monkeypox virus has been undergoing novel mutations at an alarming rate. Treatment options for monkeypox are an area that still requires extensive research, and the utility of certain antiviral medications in treating monkeypox infection is currently being explored but is still controversial and debatable.
PubMed: 37700987
DOI: 10.7759/cureus.43322 -
PeerJ 2023Carp edema virus disease (CEVD), also known as koi sleepy disease (KSD), represents a serious threat to the carp industry. The expression of immune-related genes to CEV...
Carp edema virus disease (CEVD), also known as koi sleepy disease (KSD), represents a serious threat to the carp industry. The expression of immune-related genes to CEV infections could lead to the selection of crucial biomarkers of the development of the disease. The expression of a total of eleven immune-related genes encoding cytokines (IL-1, IL-10, IL-6a, and TNF-2), antiviral response (Mx2), cellular receptors (CD4, CD8b1, and ), immunoglobulin (IgM), and genes encoding-mucins was monitored in gills of four differently KSD-susceptible strains of carp (Amur wild carp, Amur Sasan, AS; Ropsha scaly carp, Rop; Prerov scaly carp, PS; and koi) on days 6 and 11 post-infection. Carp strains were infected through two cohabitation infection trials with CEV genogroups I or IIa. The results showed that during the infection with both CEV genogroups, KSD-susceptible koi induced an innate immune response with significant up-regulation ( < 0.05) of IL-1, IL-10, IL-6a, and TNF-2 genes on both 6 and 11 days post-infection (dpi) compared to the fish sampled on day 0. Compared to koi, AS and Rop strains showed up-regulation of IL-6a and TNF-2 but no other cytokine genes. During the infection with CEV genogroup IIa, Mx2 was significantly up-regulated in all strains and peaked on 6 dpi in AS, PS, and Rop. In koi, it remained high until 11 dpi. With genogroup I infection, Mx2 was up-expressed in koi on 6 dpi and in PS on both 6 and 11 dpi. No significant differences were noticed in selected mucin genes expression measured in gills of any carp strains exposed to both CEV genogroups. During both CEV genogroups infections, the expression levels of most of the genes for T cell response, including CD4, CD8b1, and were down-regulated in AS and koi at all time points compared to day 0 control. The expression data for the above experimental trials suggest that both CEV genogroups infections in common carp strains lead to activation of the same expression pattern regardless of the fish's susceptibility towards the virus. The expression of the same genes in AS and koi responding to CEV genogroup IIa infection in mucosal tissues such as gill, gut, and skin showed the significant up-regulation of all the cytokine genes in gill and gut tissues from koi carp at 5 dpi. Significant down-regulation of CD4 and levels were only detected in koi gill on 5 dpi but not in other tissues. AS carp displayed significant up-expression of Mx2 gene in all mucosal tissues on 5 dpi, whereas in koi, it was up-regulated in gill and gut only. In both carp strains, gill harbored a higher virus load on 5 dpi compared to the other tissues. The results showed that resistance to CEV could not be linked with the selected immune responses measured. The up-regulation of mRNA expression of most of the selected immune-related genes in koi gill and gut suggests that CEV induces a more systemic mucosal immune response not restricted to the target tissue of gills.
Topics: Animals; Poxviridae Infections; Interleukin-10; Carps; Fish Diseases; Poxviridae; Immunity; Edema
PubMed: 37465154
DOI: 10.7717/peerj.15614 -
Emerging Infectious Diseases Dec 2023During the 2022 multinational outbreak of monkeypox virus (MPXV) infection, the antiviral drug tecovirimat (TPOXX; SIGA Technologies, Inc., https://www.siga.com) was...
During the 2022 multinational outbreak of monkeypox virus (MPXV) infection, the antiviral drug tecovirimat (TPOXX; SIGA Technologies, Inc., https://www.siga.com) was deployed in the United States on a large scale for the first time. The MPXV F13L gene homologue encodes the target of tecovirimat, and single amino acid changes in F13 are known to cause resistance to tecovirimat. Genomic sequencing identified 11 mutations previously reported to cause resistance, along with 13 novel mutations. Resistant phenotype was determined using a viral cytopathic effect assay. We tested 124 isolates from 68 patients; 96 isolates from 46 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of tecovirimat treatment, whereas most isolates identified by routine surveillance of patients not treated with tecovirimat remained sensitive. The frequency of resistant viruses remains relatively low (<1%) compared with the total number of patients treated with tecovirimat.
Topics: Humans; United States; Mpox (monkeypox); Antiviral Agents; Benzamides; Biological Assay; Monkeypox virus
PubMed: 37856204
DOI: 10.3201/eid2912.231146 -
Nature Communications Nov 2023Poxviruses are unusual DNA viruses that replicate in the cytoplasm. To do so, they encode approximately 100 immunomodulatory proteins that counteract cytosolic nucleic...
Poxviruses are unusual DNA viruses that replicate in the cytoplasm. To do so, they encode approximately 100 immunomodulatory proteins that counteract cytosolic nucleic acid sensors such as cGAMP synthase (cGAS) along with several other antiviral response pathways. Yet most of these immunomodulators are expressed very early in infection while many are variable host range determinants, and significant gaps remain in our understanding of poxvirus sensing and evasion strategies. Here, we show that after infection is established, subsequent progression of the viral lifecycle is sensed through specific changes to mitochondria that coordinate distinct aspects of the antiviral response. Unlike other viruses that cause extensive mitochondrial damage, poxviruses sustain key mitochondrial functions including membrane potential and respiration while reducing reactive oxygen species that drive inflammation. However, poxvirus replication induces mitochondrial hyperfusion that independently controls the release of mitochondrial DNA (mtDNA) to prime nucleic acid sensors and enables an increase in glycolysis that is necessary to support interferon stimulated gene (ISG) production. To counter this, the poxvirus F17 protein localizes to mitochondria and dysregulates mTOR to simultaneously destabilize cGAS and block increases in glycolysis. Our findings reveal how the poxvirus F17 protein disarms specific mitochondrially orchestrated responses to later stages of poxvirus replication.
Topics: Poxviridae; Cytoplasm; Nucleotidyltransferases; Antiviral Agents; Nucleic Acids
PubMed: 38036506
DOI: 10.1038/s41467-023-43635-y