The role of receptors in the cross-species spread of coronaviruses infecting humans and pigs.

The pandemic caused by SARS-CoV-2, which has proven capable of infecting over 30 animal species, highlights the critical need for understanding the mechanisms of cross-species transmission and the emergence of novel coronavirus strains. The recent discovery of CCoV-HuPn-2018, a recombinant alphacoronavirus from canines and felines that can infect humans, along with evidence of SARS-CoV-2 infection in pig cells, underscores the potential for coronaviruses to overcome species barriers. This review investigates the origins and cross-species transmission of both human and porcine coronaviruses, with a specific emphasis on the instrumental role receptors play in this process.

Lead induces mouse skin fibroblast apoptosis by disrupting intracellular homeostasis.

Lead (Pb) is a critical industrial and environmental contaminant that can cause pathophysiological changes in several cellular and organ systems and their processes, including cell proliferation, differentiation, apoptosis, and survival. The skin is readily exposed to and damaged by Pb, but the mechanisms through which Pb damages cells are not fully understood. We examined the apoptotic properties of Pb in mouse skin fibroblast (MSF) in vitro. Treatment of fibroblasts with 40, 80, and 160 µM Pb for 24 h revealed morphological alterations, DNA damage, enhanced caspase-3, -8, and -9 activities, and apoptotic cell population. Furthermore, apoptosis was dosage (0-160 µM) and time (12-48 h) dependent. Concentrations of intracellular calcium (Ca2+) and reactive oxygen species were increased, and the mitochondrial membrane potential was decreased in exposed cells. Cell cycle arrest was evident at the G0/G1 phase. The Bax, Fas, caspase-3 and -8, and p53 transcript levels were increased, whereas Bcl-2 gene expression was decreased. Based on our analysis, Pb triggers MSF apoptosis bydisrupting intracellular homeostasis. Our findings enrich the knowledge about the mechanistic function of Pb-induced cytotoxicity on human skin fibroblasts and could potentially guide future Pb health risk assessments.

Corrigendum to: Emergence and evolution of highly pathogenic porcine epidemic diarrhea virus by natural recombination of a low pathogenic vaccine isolate and a highly pathogenic strain in the spike gene.

[This corrects the article DOI: 10.1093/ve/veaa049.].

Expression pattern of interferon-inducible transcriptional genes in neutrophils during bovine tuberculosis infection.

Mycobacterium bovis, the classical causative agent of bovine tuberculosis (BTB), infects animals of agricultural importance and other mammals, including humans. Neutrophils are one of the first lines of defense against all microbes and produce a diverse collection of antimicrobial molecules, which play an important role in the early control of tuberculosis progression. An interferon (IFN)-inducible neutrophil-driven blood transcriptional signature that consisted of both IFN-γ and type I IFN-α/ß signaling has been identified in human tuberculosis, supporting a role for neutrophils in the pathogenesis of tuberculosis disease. However, it is unknown whether bovine neutrophils play a similar role during M. bovis infection. Thus, we assessed the expression levels of ten IFN-inducible transcriptional genes in neutrophils from healthy cattle stimulated by M. bovis and neutrophils isolated from three groups of cattle of different infection status, and in addition, examined the changes in the expression of myeloperoxidase (MPO) and pentraxin-related protein pentraxin-inducible protein (PTX3) genes during bovine tuberculosis infection. Our results demonstrated a specific expression pattern of IFN-inducible transcriptional genes and MPO and PTX3 genes in neutrophils during bovine tuberculosis infection. The observed expression pattern provides a potential diagnostic tool, which may have implications for vaccine and therapeutic development to combat the bovine tuberculosis epidemic.

Using protein misfolding cyclic amplification generates a highly neurotoxic PrP dimer causing neurodegeneration.

Under the "protein-only" hypothesis, prion-based diseases are proposed to result from an infectious agent that is an abnormal isoform of the prion protein in the scrapie form, PrP(Sc). However, since PrP(Sc) is highly insoluble and easily aggregates in vivo, this view appears to be overly simplistic, implying that the presence of PrP(Sc) may indirectly cause neurodegeneration through its intermediate soluble form. We generated a neurotoxic PrP dimer with partial pathogenic characteristics of PrP(Sc) by protein misfolding cyclic amplification in the presence of 1-palmitoyl-2-oleoylphosphatidylglycerol consisting of recombinant hamster PrP (23-231). After intracerebral injection of the PrP dimer, wild-type hamsters developed signs of neurodegeneration. Clinical symptoms, necropsy findings, and histopathological changes were very similar to those of transmissible spongiform encephalopathies. Additional investigation showed that the toxicity is primarily related to cellular apoptosis. All results suggested that we generated a new neurotoxic form of PrP, PrP dimer, which can cause neurodegeneration. Thus, our study introduces a useful model for investigating PrP-linked neurodegenerative mechanisms.

Expression and distribution of laminin receptor precursor/laminin receptor in rabbit tissues.

The 37/67-kDa laminin receptor precursor (LRP)/laminin receptor (LR) is a cell surface receptor for cellular prion proteins and misfolded pathological prions. Previous research has shown that blocking or decreasing LRP/LP levels by anti-LRP/LR antibodies or small interfering RNAs (siRNAs) can prolong the incubation phase of experimental prion infection. This study aimed to investigate potential mechanisms contributing to prion resistance/susceptibility by using the rabbit, a species unsusceptible to prion infection, as a model. We investigated the expression level and distribution of LRP/LR in rabbit tissues by real-time polymerase chain reaction and by immunochemical analysis with a monoclonal anti-67 kDa LR antibody. Our results showed LRP/LR mRNA expression in all the tissues examined. Very low LRP/LR expression levels were observed in central nervous system (CNS) tissues, whereas high expression levels were observed in reproductive and digestive tissues, which differed from the expression patterns that have been reported for prion-susceptible animals. The immunochemical staining results were generally consistent with the mRNA findings, although no LR protein was detected in CNS tissues. Our findings provide a basis for further studies on prion resistance in rabbits and other animal species.