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Genomic epidemiology of clade Ia monkeypox viruses circulating in the Central African Republic in 2022-24: a retrospective cross-sectional study.

BACKGROUND: The spread of monkeypox virus (Orthopoxvirus monkeypox) clade Ib from the Democratic Republic of the Congo to neighbouring countries has raised global concerns, leading to WHO declaring mpox a public health emergency on Aug 14, 2024. We applied genomic epidemiology to investigate the causes of recurrent mpox outbreaks in the Central African Republic. We aimed to determine whether frequent zoonotic spillovers or increased human-to-human transmissions are driving mpox epidemiology. METHODS: We performed a retrospective cross-sectional study of monkeypox virus genomic sequences among…

What a Difference a Gene Makes: Identification of Virulence Factors of Cowpox Virus.

Cowpox virus (CPXV) is a zoonotic orthopoxvirus (OPV) that causes spillover infections from its animal hosts to humans. In 2009, several human CPXV cases occurred through transmission from pet rats. An isolate from a diseased rat, RatPox09, exhibited significantly increased virulence in Wistar rats and caused high mortality compared to that caused by the mildly virulent laboratory strain Brighton Red (BR). The RatPox09 genome encodes four genes which are absent in the BR genome. We hypothesized that their gene products could be major factors influencing the high virulence of RatPox09. To addre…

Immune responses associated with mpox viral clearance in men with and without HIV in Spain: a multisite, observational, prospective cohort study.

BACKGROUND: Since the emergence of the global mpox outbreak in May, 2022, more than 90 000 cases have been diagnosed across 110 countries, d … rations 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. INT …

Evidence synthesis of Chinese medicine for monkeypox: Suggestions from other contagious pox-like viral diseases.

Background: Monkeypox, a zoonotic disease caused by an Orthopoxvirus, presents an etiology similar to smallpox in humans. Currently, there are no licensed treatments for human monkeypox, so clear and urgent research on its prophylaxis and treatment is needed. Objective: The purpose of this study was to explore the evidence of Chinese medicine for contagious pox-like viral diseases and provide suggestions for the multi-country outbreak management of monkeypox. Methods: The review was registered on INPLASY (INPLASY202270013). Ancient classics in China and clinical trials involving randomized con…

Vaccinia virus gene A36R encodes a M(r) 43-50 K protein on the surface of extracellular enveloped virus.

A characterization of vaccinia virus strain Western Reserve (WR) open reading frame (ORF) A36R is described. This ORF is predicted to encode a 221-amino-acid protein (M(r) 25.1 K) with an amino-terminal hydrophobic sequence, seven potential sites for attachment of N-linked carbohydrate, but no carboxy-terminal transmembrane anchor. It is identical in vaccinia strain Copenhagen and shares 94.6% amino acid identity with the corresponding ORF in variola virus strains Harvey, India-1967, and Bangladesh-1975. RNA analyses detected a 600-nucleotide, early transcript that initiated 10-13 nucleotides

Mpox in people with past infection or a complete vaccination course: a global case series.

BACKGROUND: Since May, 2022, a large global outbreak of human mpox (formerly known as monkeypox) has predominantly affected men who have sex with men. The strain responsible, Clade IIb, has mutated substantially from precursors originating from the 2017-18 outbreak in Nigeria. Immunity to smallpox, another orthopoxvirus, via previous infection or vaccination provides lifelong immunity. However, since the 2022 mpox outbreak, recent clusters were described in individuals with presumed immunity through recent infection or vaccination. We aim to describe the epidemiological and clinical characteri…

When a neglected tropical disease goes global: early estimates from the Monkeypox outbreak, the first 1,054 cases.

Monkeypox virus (MPXV), genus Orthopoxvirus, is a large double-stranded DNA virus (200-250 nm), that is evolutionarily related to human variola virus (VARV) (1), and causes a clinical syndrome quite similar to smallpox, with a generally less severe outcome (1,2). MPXV has a wide range of hosts and reservoirs in wild animals, and since 1970 has been commonly acknowledged as a human pathogen, endemic to Central and Western African countries through two distinctive clades (2,3). Central African clade (CAC) is responsible of the majority of 20,000 incident cases of the last decade, with a case-fat…

Triple-Negative Breast Cancer: Basic Biology and Immuno-Oncolytic Viruses.

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. TNBC diagnoses account for approximately one-fifth of all breast cancer cases globally. The lack of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER-2, CD340) results in a lack of available molecular-based therapeutics. This increases the difficulty of treatment and leaves more traditional as well as toxic therapies as the only available standards of care in many cases. Recurrence is an additional serious problem, contributing substantially to its higher mortality rate as compared to

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… Vaccinia Virus VV is a dsDNA Orthopoxvirus in the family Poxviridae . It is a prominent poxvirus in many cancer studies due to its large genome, which can handle many genetic inserts simultaneously, the fact that it replicates quickly, and due to it having a known safety profile. … A Novel Oncolytic Chimeric Orthopoxvirus Encoding Luciferase Enables Real-Time View of Colorectal Cancer Cell Infection Mol. Ther. Oncolytics 2018 9 13 21 10.1016/j.omto.2018.03.001 29988502 PMC6026443 136. Chaurasiya S. Yang A. Zhang Z. Lu J. Valencia H. Kim S.I. Woo Y. Warner S.G. Olafsen T. …

Safety and immunogenicity of mRNA-based mpox vaccine candidate BNT166a: an open-label, dose-escalation, first-in-human trial.

BACKGROUND: Recent mpox outbreaks highlight the need for novel, effective, and scalable vaccines against monkeypox virus (MPXV). The quadrivalent mRNA vaccine candidate BNT166a encoding MPXV antigens A35, B6, M1, and H3 was selected for clinical development based on evidence of immunogenicity and protective efficacy against multiple orthopoxviruses in preclinical models. We aimed to investigate the safety and immunogenicity of BNT166a in healthy adults. METHODS: In this open-label, uncontrolled, non-randomised, dose-escalation, first-in-human, phase 1 trial, we included healthy adults with no…

Chemistry and Pharmacology of Fluorinated Drugs Approved by the FDA (2016-2022).

Fluorine is characterized by high electronegativity and small atomic size, which provide this molecule with the unique property of augmenting the potency, selectivity, metabolic stability, and pharmacokinetics of drugs. Fluorine (F) substitution has been extensively explored in drug research as a means of improving biological activity and enhancing chemical or metabolic stability. Selective F substitution onto a therapeutic or diagnostic drug candidate can enhance several pharmacokinetic and physicochemical properties such as metabolic stability and membrane permeation. The increased binding a

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… It inhibits the orthopoxvirus VP37 envelope-wrapping protein. Patients with immune deficiencies may experience a decrease in the effectiveness of this drug. In Europe, after receiving a smallpox vaccination, it is also recommended to treat issues brought on by the replication of the vaccinia virus. … All orthopoxviruses examined in vitro, including variola and the smallpox virus, are resistant to this drug. After oral administration of 600 mg of tecovirimat and intravenous administration of 200 mg of tecovirimat, this drug shows a volume of distribution of 383 L and 1030 L, respectively. …

Best of JACC: Case Reports From ACC.23.

This dedicated issue of JACC: Case Reports highlights the top ranked Complex Clinical Cases from the ACC 2023 Scientific Sessions. These cases were reviewed and selected by a committee of peers in the months leading up to the annual meeting. These reviewers were ACC members with no affiliation to the JACC: Case Reports Editorial Board. While the cases were presented at the meeting and included in the formal Abstract Book from ACC, they have not been published elsewhere. These cases illustrate how the ACC can be a place for cardiovascular professionals to come together to learn, grow, and share

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… Mester, Doniya Milani, HCA Florida Brandon Hospital, Tampa, FL, USA Background Human Monkeypox is a zoonotic orthopoxvirus previously endemic to Western and Central Africa. An increased incidence of the virus worldwide has led to identification of novel clinical manifestations. … There is evidence that tecovirimat decreases mortality after infection with orthopoxviruses in animal studies. Conclusion This case report demonstrates further evidence that Monkeypox infection, like other viral illnesses, may result in acute myocarditis. …

Correlative analysis from a phase I clinical trial of intrapleural administration of oncolytic vaccinia virus (Olvi-vec) in patients with malignant pleural mesothelioma.

BackgroundThe attenuated, genetically engineered vaccinia virus has been shown to be a promising oncolytic virus for the treatment of patients with solid tumors, through both direct cytotoxic and immune-activating effects. Whereas systemically administered oncolytic viruses can be neutralized by pre-existing antibodies, locoregionally administered viruses can infect tumor cells and generate immune responses. We conducted a phase I clinical trial to investigate the safety, feasibility and immune activating effects of intrapleural administration of oncolytic vaccinia virus (NCT01766739).MethodsE

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… As a member of the poxvirus family of the genus orthopoxvirus, the vaccinia virus is one such oncolytic virus that possesses multiple favorable features for use as a therapeutic agent. …

Integumentary System

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Combination strategies of gut microbiota in cancer therapy through metabolic reprogramming and immune remodeling.

Over the past decade, there has been a qualitative improvement in the understanding of gut microbiota in cancer development and treatment. Gut microbiota regulates metabolic reprogramming that occurs in the competition between tumor cells and immune cells for essential nutrients in the tumor microenvironment (TME). Besides, gut microbiota dysbiosis is one of the key factors leading to the formation of aging environment, which has many similarities with the TME. Accumulating research findings have demonstrated that gut microbiota enhances the efficacy of cancer therapies by activating the immun

Recent Advances in Cancer Vaccines: Challenges, Achievements, and Futuristic Prospects.

Cancer is a chronic disease, and it can be lethal due to limited therapeutic options. The conventional treatment options for cancer have numerous challenges, such as a low blood circulation time as well as poor solubility of anticancer drugs. Therapeutic cancer vaccines emerged to try to improve anticancer drugs' efficiency and to deliver them to the target site. Cancer vaccines are considered a viable therapeutic technique for most solid tumors. Vaccines boost antitumor immunity by delivering tumor antigens, nucleic acids, entire cells, and peptides. Cancer vaccines are designed to induce lon

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… Hepatitis virus C, HBV, Alphaviruses, Adenoviruses, and viruses from the Orthopoxvirus genera, as well as the extracts of Vaccinia virus, and even the members of the Avipoxvirus genera, such as the Fowlpox and Canarypox, are perhaps the most prevalent viruses used for the development and progression …

Respiratory and Thoracic Medicine

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The investigation of oncolytic viruses in the field of cancer therapy.

Oncolytic viruses (OVs) have emerged as a potential strategy for tumor treatment due to their ability to selectively replicate in tumor cells, induce apoptosis, and stimulate immune responses. However, the therapeutic efficacy of single OVs is limited by the complexity and immunosuppressive nature of the tumor microenvironment (TME). To overcome these challenges, engineering OVs has become an important research direction. This review focuses on engineering methods and multi-modal combination therapies for OVs aimed at addressing delivery barriers, viral phagocytosis, and antiviral immunity in

Oncolytic virus-based hepatocellular carcinoma treatment: Current status, intravenous delivery strategies, and emerging combination therapeutic solutions.

Current treatments for advanced hepatocellular carcinoma (HCC) have limited success in improving patients' quality of life and prolonging life expectancy. The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies. Recently, there has been increased interest in oncolytic viruses (OVs) as a therapeutic modality for HCC. OVs undergo selective replication in cancerous tissues and kill tumor cells. Strikingly, pexastimogene devacirepvec (Pexa-Vec) was granted an orphan drug status in HCC by the U.S. Food and Drug Administration (FDA) in 2013.

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… Oncolytic vaccinia virus (VV) VV is a member of the orthopoxvirus genus in the family Poxviridae. It is a double-stranded DNA virus with a genome size of ∼190 kb [70] . The biological characteristics of VV are as follows: (a) VV quickly replicates in cancer cells and lyses them. …

The multiple roles of interferon regulatory factor family in health and disease.

Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores the diverse functions of nine mammalian IRF members, each featuring conserved domains essential for interactions with other transcription factors and cofactors. These interactions allow IRFs to modulate a broad spectrum of physiological processes, encompassing host defense, immune response, and cell development. Conversely, their pivotal role in immune regulation implicates them in the pathophysiology of v

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… inflammasome, mediating inflammatory and cell death responses in IAV infection. 271 In addition, IRF1 is required for optimal early activation of IRF3, targeting and augmenting IRF3 phosphorylation, which enhances innate immunity to viral infection. 168 , 322 IRF2 is also identified to inhibit ZIKV and orthopoxvirus …

Oncolytic myxoma virus and engineering strategies for advanced cancer immunotherapy.

In cancer immunotherapy, oncolytic viruses (OVs) offer an alternative approach to kill malignant cells by inducing cancer-specific host immune system activation. Given the ongoing need for safe and effective viral vectors for immunotherapy, non-zoonotic animal viruses have attracted significant interest. Here, we review the oncolytic myxoma virus (MYXV) and emphasize its emerging role in cancer immunotherapy. We critically discuss recent advances in cancer therapy using MYXV, primarily focused on engineered viral modifications. Furthermore, we briefly review alternative delivery strategies for

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… . | predicted | 13 , 15 , 32 M143R | M143R is a homolog of the RING-containing ubiquitin ligase p28 of orthopoxviruses and mediates the formation of polyubiquitin conjugates. … Genes in the terminal regions of orthopoxvirus genomes experience adaptive molecular evolution. BMC Genom. 2011;12:261. doi: 10.1186/1471-2164-12-261. 28. Barry M., Hnatiuk S., Mossman K., Lee S.F., Boshkov L., McFadden G. …