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Poxviruses are often thought to evolve relatively slowly because they are double-stranded DNA pathogens with proofreading polymerases. However, poxviruses have highly adaptable genomes and can undergo relatively rapid genotypic and phenotypic change, as illustrated by the recent increase in human-to-human transmission of monkeypox virus. Advances in deep sequencing technologies have demonstrated standing nucleotide variation in poxvirus populations, which has been underappreciated. There is also an emerging understanding of the role genomic architectural changes play in shaping poxvirus evolution. These mechanisms include homologous and nonhomologous recombination, gene duplications, gene loss, and the acquisition of new genes through horizontal gene transfer. In this review, we discuss these evolutionary mechanisms and their potential roles for adaption to novel host species and modulating virulence.

Myxoma virus (MYXV) causes localized cutaneous fibromas in its natural hosts, tapeti and brush rabbits; however, in the European rabbit, MYXV causes the lethal disease myxomatosis. Currently, the molecular mechanisms underlying this increased virulence after cross-species transmission are poorly understood. In this study, we investigated the interaction between MYXV M156 and the host protein kinase R (PKR) to determine their crosstalk with the proinflammatory nuclear factor kappa B (NF-κB) pathway. Our results demonstrated that MYXV M156 inhibits brush rabbit PKR (bPKR) more strongly than European rabbit PKR (ePKR). This moderate ePKR inhibition could be improved by hyperactive M156 mutants. We hypothesized that the moderate inhibition of ePKR by M156 might incompletely suppress the signal transduction pathways modulated by PKR, such as the NF-κB pathway. Therefore, we analyzed NF-κB pathway activation with a luciferase-based promoter assay. The moderate inhibition of ePKR resulted in significantly higher NF-κB–dependent reporter activity than complete inhibition of bPKR. We also found a stronger induction of the NF-κB target genes TNFα and IL-6 in ePKR-expressing cells than in bPKR-expressing cells in response to M156 in both transfection and infections assays. Furthermore, a hyperactive M156 mutant did not cause ePKR-dependent NF-κB activation. These observations indicate that M156 is maladapted for ePKR inhibition, only incompletely blocking translation in these hosts, resulting in preferential depletion of short–half-life proteins, such as the NF-κB inhibitor IκBα. We speculate that this functional activation of NF-κB induced by the intermediate inhibition of ePKR by M156 may contribute to the increased virulence of MYXV in European rabbits.

Host pattern recognition receptors (PRRs) sense pathogen-associated molecular patterns (PAMPs), which are molecular signatures shared by different pathogens. Recognition of PAMPs by PRRs initiate innate immune responses via diverse signaling pathways. Over recent decades, advances in our knowledge of innate immune sensing have enhanced our understanding of the host immune response to poxviruses. Multiple PRR families have been implicated in poxvirus detection, mediating the initiation of signaling cascades, activation of transcription factors, and, ultimately, the expression of antiviral effectors. To counteract the host immune defense, poxviruses have evolved a variety of immunomodulators that have diverse strategies to disrupt or circumvent host antiviral responses triggered by PRRs. These interactions influence the outcomes of poxvirus infections. This review focuses on our current knowledge of the roles of PRRs in the recognition of poxviruses, their elicited antiviral effector functions, and how poxviral immunomodulators antagonize PRR-mediated host immune responses.

Prolonged and excessive accumulation of β2-microglobulin (β2m) in the blood can lead to various kidney-related and other diseases. Currently, the most effective method of removing β2m from the blood is hemoperfusion. Although some traditional hemoperfusion adsorbents such as cellulose and polystyrene microspheres have been used for the removal of β2m, their selectivity still needs improvement. Immunosorbents have been developed to address this issue, but high cost and limited application are concerns. TiO2 nanotube arrays (TNTAs) have shown great potential in adsorption-related biomedical applications. In this study, we designed and developed a novel TNTA-based hemoperfusion adsorbent for the removal of β2m, which has demonstrated good biocompatibility, selectivity, and reusability. We investigated the β2m adsorption capacities of TNTAs with different pore sizes. The results indicate that TNTAs with a pore size matching the size of β2m exhibit higher adsorption capacity while also having lower adsorption capacity for albumin, showing the importance of pore size on the selectivity of adsorbents. Additionally, green regeneration of TNTAs is achieved via the photocatalytic activity originating from TiO2. Even after five cycles, the adsorption capacity of TNTAs remained above 70%. Our work demonstrates that inorganic materials with ordered pores are capable to be candidates for hemoperfusion, possessing advantages over traditional organic materials such as high stability, security, and low cost. [ABSTRACT FROM AUTHOR]

To identify the influences of anthropogenic activities on the composition, spatial distribution, sources, and transformation mechanism of sedimentary fulvic acid (FA) fractions from different reaches of an urban river were tracked via excitation-emission matrix (EEM) fluorescence spectroscopy with parallel factor (PARAFAC) analysis and two-dimensional correlation spectroscopy (2D-COS). Sediment samples were collected from Baitapu River (BR) along gradients with human activities (e.g., rural, town, and urban sections) in Shenyang, northeast China, from which FA fractions were extracted and then determined via EEM fluorescence spectroscopy. According to optical indices, the autochthonous sources of sedimentary FA fractions in BR were more significant than the terrestrial sources. Among the sections, the contribution from autochthonous sources decreased in the following order: Rural > Urban > Town. Six components of sedimentary FA fractions were identified via EEM–PARAFAC: C1 comprised tryptophan-like (TRL) compounds; C2 was associated with microbial humic-like (MHL) compounds; C3, C4, and C5 were associated with FA-like (FAL) compounds; and C6 comprised humic acid-like (HAL) compounds. The proportion of sedimentary FA fractions decreased in the following order: MHL + FAL + HAL (humus, 77.37–88.90%) > TRL (protein, 11.10–22.63%) for the three sections, showing that humus dominated. The town section exhibited the highest sedimentary FA fractions (5328.87 ± 1315.82 Raman unit [R.U.]), followed by the urban (4146.49 ± 535.75 R.U.) and rural (2510.56 ± 611.00 R.U.) sections. Three pollution sources were determined via principal component analysis (i.e., the dominant industrial source, domestic wastewater, and agricultural effluent). Additionally, the results from 2D-COS revealed that sedimentary FA fractions tended to stabilize as the protein-like component was transformed into the HAL component. Furthermore, we used the structural equation model to validate the critical environmental variables affecting the FA fraction transformation. The results can elucidate the influences of human activities on the dynamics of sedimentary FA fractions in urban rivers. [ABSTRACT FROM AUTHOR]