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Nature Communications May 2024Understanding of infection dynamics is important for public health measures against monkeypox virus (MPXV) infection. Herein, samples from multiple body sites and...
Understanding of infection dynamics is important for public health measures against monkeypox virus (MPXV) infection. Herein, samples from multiple body sites and environmental fomites of 77 acute MPXV infections (HIV co-infection: N = 42) were collected every two to three days and used for detection of MPXV DNA, surface protein specific antibodies and neutralizing titers. Skin lesions show 100% positivity rate of MPXV DNA, followed by rectum (88.16%), saliva (83.78%) and oropharynx (78.95%). Positivity rate of oropharynx decreases rapidly after 7 days post symptom onset (d.p.o), while the rectum and saliva maintain a positivity rate similar to skin lesions. Viral dynamics are similar among skin lesions, saliva and oropharynx, with a peak at about 6 d.p.o. In contrast, viral levels in the rectum peak at the beginning of symptom onset and decrease rapidly thereafter. 52.66% of environmental fomite swabs are positive for MPXV DNA, with highest positivity rate (69.89%) from air-conditioning air outlets. High seropositivity against A29L (100%) and H3L (94.74%) are detected, while a correlation between IgG endpoint titers and neutralizing titers is only found for A29L. Most indexes are similar between HIV and Non-HIV participants, while HIV and rectitis are associated with higher viral loads in rectum.
Topics: Humans; Male; Virus Shedding; Antibodies, Viral; Prospective Studies; Adult; Monkeypox virus; Mpox (monkeypox); Saliva; HIV Infections; Antibodies, Neutralizing; Middle Aged; Longitudinal Studies; DNA, Viral; Oropharynx; Coinfection; Viral Load; Fomites
PubMed: 38802350
DOI: 10.1038/s41467-024-48754-8 -
Viruses May 2024Epidemiologic studies have established that mpox (formerly known as monkeypox) outbreaks worldwide in 2022-2023, due to Clade IIb mpox virus (MPXV), disproportionately... (Review)
Review
Epidemiologic studies have established that mpox (formerly known as monkeypox) outbreaks worldwide in 2022-2023, due to Clade IIb mpox virus (MPXV), disproportionately affected gay, bisexual, and other men who have sex with men. More than 35% and 40% of the mpox cases suffer from co-infection with HIV and sexually transmitted infections (STIs) (e.g., , and herpes simplex virus), respectively. Bacterial superinfection can also occur. Co-infection of MPXV and other infectious agents may enhance disease severity, deteriorate outcomes, elongate the recovery process, and potentially contribute to the morbidity and mortality of the ensuing diseases. However, the interplays between MPXV and HIV, bacteria, other STI pathogens and host cells are poorly studied. There are many open questions regarding the impact of co-infections with HIV, STIs, or bacterial superinfections on the diagnosis and treatment of MPXV infections, including clinical and laboratory-confirmed mpox diagnosis, suboptimal treatment effectiveness, and induction of antiviral drug resistance. In this review article, we will discuss the progress and knowledge gaps in MPXV biology, antiviral therapy, pathogenesis of human MPXV and its co-infection with HIV, STIs, or bacterial superinfections, and the impact of the co-infections on the diagnosis and treatment of mpox disease. This review not only sheds light on the MPXV infection and co-infection of other etiologies but also calls for more research on MPXV life cycles and the molecular mechanisms of pathogenesis of co-infection of MPXV and other infectious agents, as well as research and development of a novel multiplex molecular testing panel for the detection of MPXV and other STI co-infections.
Topics: Humans; Male; Coinfection; HIV Infections; Monkeypox virus; Mpox (monkeypox); Sexually Transmitted Diseases; Superinfection; Female
PubMed: 38793665
DOI: 10.3390/v16050784 -
Viruses May 2024Lumpy skin disease is one of the fast-spreading viral diseases of cattle and buffalo that can potentially cause severe economic impact. Lesotho experienced LSD for the...
Lumpy skin disease is one of the fast-spreading viral diseases of cattle and buffalo that can potentially cause severe economic impact. Lesotho experienced LSD for the first time in 1947 and episodes of outbreaks occurred throughout the decades. In this study, eighteen specimens were collected from LSD-clinically diseased cattle between 2020 and 2022 from Mafeteng, Leribe, Maseru, Berea, and Mohales' Hoek districts of Lesotho. A total of 11 DNA samples were analyzed by PCR and sequencing of the extracellular enveloped virus (EEV) glycoprotein, G-protein-coupled chemokine receptor (GPCR), 30 kDa RNA polymerase subunit (RPO30), and B22R genes. All nucleotide sequences of the above-mentioned genes confirmed that the PCR amplicons of clinical samples are truly LSDV, as they were identical to respective LSDV isolates on the NCBI GenBank. Two of the elevem samples were further characterized by whole-genome sequencing. The analysis, based on both CaPV marker genes and complete genome sequences, revealed that the LSDV isolates from Lesotho cluster with the NW-like LSDVs, which includes the commonly circulating LSDV field isolates from Africa, the Middle East, the Balkans, Turkey, and Eastern Europe.
Topics: Animals; Cattle; Lumpy Skin Disease; Lesotho; Lumpy skin disease virus; Phylogeny; Whole Genome Sequencing; Genome, Viral
PubMed: 38793643
DOI: 10.3390/v16050762 -
Viruses May 2024In 2022, an unprecedented outbreak of mpox raged in several nations. Sequences from the 2022 outbreak reveal a higher nucleotide substitution if compared with the...
In 2022, an unprecedented outbreak of mpox raged in several nations. Sequences from the 2022 outbreak reveal a higher nucleotide substitution if compared with the estimated rate for orthopoxviruses. Recently, intra-lesion SNVs (single nucleotide variants) have been described, and these have been suggested as possible sources of genetic variation. Until now, it has not been clear if the presence of several SNVs could represents the result of local mutagenesis or a possible co-infection. We investigated the significance of SNVs through whole-genome sequencing analysis of four unrelated mpox cases. In addition to the known mutations harboured by the circulating strains of virus (MPXV), 7 novel mutations were identified, including SNVs located in genes that are involved in immune evasion mechanisms and/or viral fitness, six of these appeared to be APOBEC3-driven. Interestingly, three patients exhibited the coexistence of mutated and wild-type alleles for five non-synonymous variants. In addition, two patients, apparently unrelated, showed an analogous pattern for two novel mutations, albeit with divergent frequencies. The coexistence of mixed viral populations, harbouring non-synonymous mutations in patients, supports the hypothesis of possible co-infection. Additional investigations of larger clinical cohorts are essential to validating intra-patient viral genome heterogeneity and determining the possibility of co-presence events of slightly divergent MPXV strains.
Topics: Humans; Genome, Viral; Italy; Disease Outbreaks; Mutation; Whole Genome Sequencing; Male; Orthopoxvirus; Poxviridae Infections; Female; Coinfection; Phylogeny; Polymorphism, Single Nucleotide; Middle Aged; Genetic Variation
PubMed: 38793608
DOI: 10.3390/v16050726 -
Viruses Apr 2024A natural monkeypox virus infection may not induce sufficient neutralizing antibody responses in a subset of healthy individuals. The aim of this study was to evaluate...
A natural monkeypox virus infection may not induce sufficient neutralizing antibody responses in a subset of healthy individuals. The aim of this study was to evaluate monkeypox virus-neutralizing antibodies six months after infection and to assess the virological factors predictive of a poor immunological response. Antibodies were assessed using a plaque reduction neutralization test at six months from mpox infection; mpox cutaneous, oropharyngeal, and anal swabs, semen, and plasma samples were tested during infection. Overall, 95 people were included in the study; all developed detectable antibodies. People who were positive for the monkeypox virus for more days had higher levels of antibodies when considering all tested samples ( = 0.029) and all swabs ( = 0.005). Mpox cycle threshold values were not predictive of antibody titers. This study found that the overall days of monkeypox virus detection in the body, irrespective of the viral loads, were directly correlated with monkeypox virus neutralizing antibodies at six months after infection.
Topics: Antibodies, Neutralizing; Humans; Antibodies, Viral; Monkeypox virus; Male; Mpox (monkeypox); Adult; Female; Middle Aged; Neutralization Tests; Viral Load; Young Adult
PubMed: 38793563
DOI: 10.3390/v16050681 -
Emerging Infectious Diseases Jun 2024The myxoma virus species jump from European rabbits (Oryctolagus cuniculus) to Iberian hares (Lepus granatensis) has raised concerns. We assess the decline suffered by...
The myxoma virus species jump from European rabbits (Oryctolagus cuniculus) to Iberian hares (Lepus granatensis) has raised concerns. We assess the decline suffered by Iberian hare populations on the Iberian Peninsula and discuss the association between the effect of myxomatosis and the average abundance index, which we estimated by using hunting bags.
Topics: Animals; Myxoma virus; Hares; Spain; Rabbits; Myxomatosis, Infectious
PubMed: 38781982
DOI: 10.3201/eid3006.231280 -
Cureus Apr 2024Background The monkeypox virus (MPXV) is classified as a zoonotic virus of the family, resulting from the MPXV strain of the genus. Seaweeds, or marine macroalgae, are...
Background The monkeypox virus (MPXV) is classified as a zoonotic virus of the family, resulting from the MPXV strain of the genus. Seaweeds, or marine macroalgae, are abundant reservoirs of bioactive compounds that demonstrate diverse biological properties, such as antiviral actions. In the field of computational analysis, in silico analysis refers to the use of computer-based methods to study and assess biological systems and processes. To forecast the binding affinity and interaction between the discovered chemical and the target proteins of the MPXV, a molecular docking analysis was conducted. Aim The research aims to conduct an in silico examination of a protein-ligand interaction of a drug produced from seaweed that targets the MPXV. Methodology Protein Data Bank (PDB) and PubChem databases provided MPXV methyltransferase and fucoxanthin ligand compounds. AutoDockTools 1.5.7 calculated the molecular docking using the Lamarckian genetic algorithm. Autogrid created a grid box around target 8B07 active site hotspot residues. Each docked molecule's docking parameters were obtained from 100 docking experiments with a maximum of 2.5 × 10 energy evaluations, a 0.02 mutation rate, and a 0.8 crossover rate. The population comprised 250 randomly selected volunteers. PyMOL was utilized to observe ligand fragment interactions. Results The binding energy of the ligand fucoxanthin was -5.46 kcal/mol. Fucoxanthin interacts with receptor molecules via hydrogen bonding at the amino acid level: Chain A: PHE188 and TYR189; and Chain B: LYS33, GLN37, GLY38, GLY96, ARG97, PHE115, PRO202, and SER203. The higher the negative docking score, the stronger the binding affinity between the receptor and ligand molecules, indicating that bioactive substances are more effective. Conclusion The findings of this study indicate that fucoxanthin, a pharmaceutical derivative generated from seaweed, had antiviral activity against the MPXV. This conclusion was reached based on protein-ligand interactions.
PubMed: 38779278
DOI: 10.7759/cureus.58730 -
PLoS Pathogens May 2024The year 2022 was marked by the mpox outbreak caused by the human monkeypox virus (MPXV), which is approximately 98% identical to the vaccinia virus (VACV) at the...
The year 2022 was marked by the mpox outbreak caused by the human monkeypox virus (MPXV), which is approximately 98% identical to the vaccinia virus (VACV) at the sequence level with regard to the proteins involved in DNA replication. We present the production in the baculovirus-insect cell system of the VACV DNA polymerase holoenzyme, which consists of the E9 polymerase in combination with its co-factor, the A20-D4 heterodimer. This led to the 3.8 Å cryo-electron microscopy (cryo-EM) structure of the DNA-free form of the holoenzyme. The model of the holoenzyme was constructed from high-resolution structures of the components of the complex and the A20 structure predicted by AlphaFold 2. The structures do not change in the context of the holoenzyme compared to the previously determined crystal and NMR structures, but the E9 thumb domain became disordered. The E9-A20-D4 structure shows the same compact arrangement with D4 folded back on E9 as observed for the recently solved MPXV holoenzyme structures in the presence and the absence of bound DNA. A conserved interface between E9 and D4 is formed by a cluster of hydrophobic residues. Small-angle X-ray scattering data show that other, more open conformations of E9-A20-D4 without the E9-D4 contact exist in solution using the flexibility of two hinge regions in A20. Biolayer interferometry (BLI) showed that the E9-D4 interaction is indeed weak and transient in the absence of DNA although it is very important, as it has not been possible to obtain viable viruses carrying mutations of key residues within the E9-D4 interface.
Topics: Vaccinia virus; DNA-Directed DNA Polymerase; Holoenzymes; Cryoelectron Microscopy; Viral Proteins; Animals; Humans; Models, Molecular; Protein Conformation; Crystallography, X-Ray
PubMed: 38768256
DOI: 10.1371/journal.ppat.1011652 -
Emerging Microbes & Infections Dec 2024Men who have sex with men and people living with HIV are disproportionately affected in the 2022 multi-country monkeypox epidemic. The smallpox vaccine can induce... (Observational Study)
Observational Study
Men who have sex with men and people living with HIV are disproportionately affected in the 2022 multi-country monkeypox epidemic. The smallpox vaccine can induce cross-reactive antibodies against the monkeypox virus (MPXV) and reduce the risk of infection. Data on antibodies against MPXV induced by historic smallpox vaccination in people with HIV are scarce. In this observational study, plasma samples were collected from people living with and without HIV in Shenzhen, China. We measured antibodies binding to two representative proteins of vaccinia virus (VACV; A27L and A33R) and homologous proteins of MPXV (A29L and A35R) using an enzyme-linked immunosorbent assay. We compared the levels of these antibodies between people living with and without HIV. Stratified analyses were performed based on the year of birth of 1981 when the smallpox vaccination was stopped in China. Plasma samples from 677 people living with HIV and 746 people without HIV were tested. A consistent pattern was identified among the four antibodies, regardless of HIV status. VACV antigen-reactive and MPXV antigen-reactive antibodies induced by historic smallpox vaccination were detectable in the people born before 1981, and antibody levels reached a nadir during or after 1981. The levels of smallpox vaccine-induced antibodies were comparable between people living with HIV and those without HIV. Our findings suggest that the antibody levels against MPXV decreased in both people living with and without HIV due to the cessation of smallpox vaccination.
Topics: Humans; Antibodies, Viral; Male; Smallpox Vaccine; HIV Infections; Adult; Female; China; Middle Aged; Monkeypox virus; Smallpox; Vaccination; Mpox (monkeypox); Cross Reactions; Young Adult; Enzyme-Linked Immunosorbent Assay; Vaccinia virus
PubMed: 38767199
DOI: 10.1080/22221751.2024.2356153 -
Cureus Apr 2024Monkeypox is a zoonotic disease caused by an enveloped single-stranded DNA virus that belongs to the Poxviridae family. It was first identified in humans in the 1970s....
Monkeypox is a zoonotic disease caused by an enveloped single-stranded DNA virus that belongs to the Poxviridae family. It was first identified in humans in the 1970s. In 2022, a monkeypox outbreak spread extensively outside of endemic countries. Monkeypox infection begins with the prodromal symptoms of fever, myalgia, and lethargy, followed by the development of a characteristic maculopapular rash. In most cases, the illness is self-limiting. However, severe cases can lead to devastating neurological complications, such as encephalitis. Here, we present the case of a 31-year-old male patient with monkeypox who developed encephalomyelitis and exhibited complete neurological recovery upon treatment with pulse steroid and intravenous immunoglobulin.
PubMed: 38765399
DOI: 10.7759/cureus.58479