In this study, we employed short- and long-read sequencing technologies to delineate the transcriptional architecture of the human monkeypox virus and to identify key regulatory elements that govern its gene expression. Specifically, we conducted a transcriptomic analysis to annotate the transcription start sites (TSSs) and transcription end sites (TESs) of the virus by utilizing Cap Analysis of gene expression sequencing on the Illumina platform and direct RNA sequencing on the Oxford Nanopore technology device. Our investigations uncovered significant complexity in the use of alternative TSSs and TESs in viral genes. In this research, we also detected the promoter elements and poly(A) signals associated with the viral genes. Additionally, we identified novel genes in both the left and right variable regions of the viral genome.IMPORTANCEGenerally, gaining insight into how the transcription of a virus is regulated offers insights into the key mechanisms that control its life cycle. The recent outbreak of the human monkeypox virus has underscored the necessity of understanding the basic biology of its causative agent. Our results are pivotal for constructing a comprehensive transcriptomic atlas of the human monkeypox virus, providing valuable resources for future studies.
- MeSH
- genom virový MeSH
- lidé MeSH
- počátek transkripce * MeSH
- promotorové oblasti (genetika) MeSH
- RNA virová genetika MeSH
- sekvenční analýza RNA * metody MeSH
- stanovení celkové genové exprese MeSH
- transkriptom * MeSH
- virus opičích neštovic genetika MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The current monkeypox virus (MPXV) strain differs from the strain arising in 2018 by 50+ single nucleotide polymorphisms (SNPs) and is mutating much faster than expected. The cytidine deaminase apolipoprotein B messenger RNA editing enzyme, catalytic subunit B (APOBEC3) was hypothesized to be driving this increased mutation. APOBEC has recently been identified to preferentially mutate cruciform DNA secondary structures formed by inverted repeats (IRs). IRs were recently identified as hot spots for mutation in severe acute respiratory syndrome coronavirus 2, and we aimed to identify whether IRs were also hot spots for mutation within MPXV genomes. We found that MPXV genomes were replete with IR sequences. Of the 50+ SNPs identified in the 2022 outbreak strain, 63.9% of these were found to have arisen within IR regions in the 2018 reference strain (MT903344.1). Notably, IR sequences found in the 2018 reference strain were significantly lost over time, with an average of 32.5% of these sequences being conserved in the 2022 MPXV genomes. This evidence was highly indicative that mutations were arising within IRs. This data provides further support to the hypothesis that APOBEC may be driving MPXV mutation and highlights the necessity for greater surveillance of IRs of MPXV genomes to detect new mutations.
- MeSH
- COVID-19 * MeSH
- lidé MeSH
- mutace MeSH
- SARS-CoV-2 MeSH
- virus opičích neštovic * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Monkeypox, or mpox, is a disease that has recently resurfaced and spread across the globe. Despite the availability of an FDA-approved vaccine (JYNNEOS) and an effective drug (tecovirimat), concerns remain over the possible recurrence of a viral pandemic. Like any other virus, mpox virus must overcome the immune system to replicate. Viruses have evolved various strategies to overcome both innate and adaptive immunity. Poxviruses possess an unusual nuclease, poxin, which cleaves 2'-3'-cGAMP, a cyclic dinucleotide, which is an important second messenger in the cGAS-STING signaling pathway. Here, we present the crystal structure of mpox poxin. The structure reveals a conserved, predominantly β-sheet fold and highlights the high conservation of the cGAMP binding site and of the catalytic residues His17, Tyr138, and Lys142. This research suggests that poxin inhibitors could be effective against multiple poxviruses.
- MeSH
- lidé MeSH
- opičí neštovice * MeSH
- Poxviridae * MeSH
- racionální návrh léčiv MeSH
- signální transdukce MeSH
- virus opičích neštovic MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Monkeypox is a disease with pandemic potential. It is caused by the monkeypox virus (MPXV), a double-stranded DNA virus from the Poxviridae family, that replicates in the cytoplasm and must encode for its own RNA processing machinery including the capping machinery. Here, we present crystal structures of its 2'-O-RNA methyltransferase (MTase) VP39 in complex with the pan-MTase inhibitor sinefungin and a series of inhibitors that were discovered based on it. A comparison of this 2'-O-RNA MTase with enzymes from unrelated single-stranded RNA viruses (SARS-CoV-2 and Zika) reveals a conserved sinefungin binding mode, implicating that a single inhibitor could be used against unrelated viral families. Indeed, several of our inhibitors such as TO507 also inhibit the coronaviral nsp14 MTase.
- MeSH
- COVID-19 * MeSH
- infekce virem zika * MeSH
- lidé MeSH
- methyltransferasy metabolismus MeSH
- RNA virová genetika MeSH
- RNA MeSH
- SARS-CoV-2 genetika MeSH
- virové nestrukturální proteiny chemie MeSH
- virus opičích neštovic genetika metabolismus MeSH
- virus zika * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Following the report of a non-travel-associated cluster of monkeypox cases by the United Kingdom in May 2022, 41 countries across the WHO European Region have reported 21,098 cases and two deaths by 23 August 2022. Nowcasting suggests a plateauing in case notifications. Most cases (97%) are MSM, with atypical rash-illness presentation. Spread is mainly through close contact during sexual activities. Few cases are reported among women and children. Targeted interventions of at-risk groups are needed to stop further transmission.
Herein, we present our findings of an early appearance of the Monkeypox virus in Prague, Czech Republic. A retrospective analysis of biological samples, carried out on the 28th of April, revealed a previously unrecognized case of Monkeypox virus (MPxV) infection. Subsequent data analysis confirmed that the virus strain belongs to the ongoing outbreak. Combined with clinical and epidemiological investigations, we extended the roots of the current outbreak at least back to 16th of April, 2022.
- MeSH
- epidemický výskyt choroby MeSH
- lidé MeSH
- opičí neštovice * epidemiologie MeSH
- retrospektivní studie MeSH
- virus opičích neštovic MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: There is a high frequency of monkeypox (MPOX) and sexually transmitted infections (STIs) in men who have sex with men (MSM). AIM: To identify the sexual behavior of MSM during the MPOX infection period. METHODS: We conducted an observational study of cases and controls were carried out. RESULTS: A total of 171 participants were considered, two heterosexual male controls (MSW) were included for each case of MSM with a consecutive selection of people who attended the STI prevention and control center from January to July 2022. The results revealed that the mean number of sexual partners reported in the last year was higher in cases (4.2) compared to controls 1.9 (p < 0.05). The related conditions for MSM to acquire some type of STI were sexual intercourse under the influence of alcohol (OR 2.42; 95% CI: 1.11-3.96), forgetting to use a protection method (condom) (OR 3.16; 95%: 1.73-7.48) and sexual intercourse with casual couples (OR 1.4; 95% CI: 1.01-2.16). CONCLUSION: Our findings demonstrated a link between the sexual behavior of men who have sex with men and the high prevalence of sexually transmitted infections during the human monkeypox virus outbreak.
- MeSH
- HIV infekce * epidemiologie prevence a kontrola MeSH
- homosexualita mužská MeSH
- koitus MeSH
- lidé MeSH
- opičí neštovice * MeSH
- sexuálně přenosné nemoci * epidemiologie prevence a kontrola MeSH
- sexuální a genderové menšiny * MeSH
- sexuální chování MeSH
- virus opičích neštovic MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- MeSH
- epidemie prevence a kontrola statistika a číselné údaje MeSH
- lidé MeSH
- opičí neštovice * diagnóza epidemiologie přenos prevence a kontrola MeSH
- přenos infekční nemoci prevence a kontrola statistika a číselné údaje MeSH
- vakcinace metody MeSH
- virus opičích neštovic MeSH
- zdroje nemoci MeSH
- Check Tag
- lidé MeSH
