-
Current Microbiology Mar 2022The recent pandemic which arose from China, is caused by a pathogenic virus named "severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2)". Its rapid... (Review)
Review
The recent pandemic which arose from China, is caused by a pathogenic virus named "severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2)". Its rapid global expansion has inflicted an extreme public health concern. The attachment of receptor-binding domains (RBD) of the spike proteins (S) to the host cell's membrane, with or without the help of other cellular components such as proteases and especially co-receptors, is required for the first stage of its pathogenesis. In addition to humans, angiotensin-converting enzyme 2 (ACE2) is found on a wide range of vertebrate host's cellular surface. SARS-CoV-2 has a broad spectrum of tropism; thus, it can infect a vast range of tissues, organs, and hosts; even though the surface amino acids of the spike protein conflict in the receptor-binding region. Due to the heterogeneous ACE2 distribution and the presence of different domains on the SARS-CoV-2 spike protein for binding, the virus entry into diverse host cell types may depend on the host cells' receptor presentation with or without co-receptors. This review investigates multiple current types of receptor and co-receptor tropisms, with other molecular factors alongside their respective mechanisms, which facilitate the binding and entry of SARS-CoV-2 into the cells, extending the severity of the coronavirus disease 2019 (COVID-19). Understanding the pathogenesis of COVID-19 from this perspective can effectively help prevent this disease and provide more potent treatment strategies, particularly in vulnerable people with various cellular-level susceptibilities.
Topics: COVID-19; Humans; Peptidyl-Dipeptidase A; Probability; Receptors, Virus; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Tropism
PubMed: 35292865
DOI: 10.1007/s00284-022-02807-7 -
Cell Host & Microbe Dec 2023Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike...
Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. Here, we show that the African Rhinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad angiotensin-converting enzyme 2 (ACE2) usage and that receptor-binding domain (RBD) mutations further expand receptor promiscuity and enable human ACE2 utilization. We determine a cryo-EM structure of the PRD-0038 RBD bound to Rhinolophus alcyone ACE2, explaining receptor tropism and highlighting differences with SARS-CoV-1 and SARS-CoV-2. Characterization of PRD-0038 S using cryo-EM and monoclonal antibody reactivity reveals its distinct antigenicity relative to SARS-CoV-2 and identifies PRD-0038 cross-neutralizing antibodies for pandemic preparedness. PRD-0038 S vaccination elicits greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses compared with SARS-CoV-2 S due to broader antigenic targeting, motivating the inclusion of clade 3 antigens in next-generation vaccines for enhanced resilience to viral evolution.
Topics: Animals; Humans; Angiotensin-Converting Enzyme 2; Severe acute respiratory syndrome-related coronavirus; Chiroptera; SARS-CoV-2; Tropism; Spike Glycoprotein, Coronavirus; Antibodies, Viral
PubMed: 37989312
DOI: 10.1016/j.chom.2023.10.018 -
Open Biology May 2019Parasitic diseases, such as sleeping sickness, Chagas disease and malaria, remain a major cause of morbidity and mortality worldwide, but particularly in tropical,... (Review)
Review
Parasitic diseases, such as sleeping sickness, Chagas disease and malaria, remain a major cause of morbidity and mortality worldwide, but particularly in tropical, developing countries. Controlling these diseases requires a better understanding of host-parasite interactions, including a deep appreciation of parasite distribution in the host. The preferred accumulation of parasites in some tissues of the host has been known for many years, but recent technical advances have allowed a more systematic analysis and quantifications of such tissue tropisms. The functional consequences of tissue tropism remain poorly studied, although it has been associated with important aspects of disease, including transmission enhancement, treatment failure, relapse and clinical outcome. Here, we discuss current knowledge of tissue tropism in Trypanosoma infections in mammals, describe potential mechanisms of tissue entry, comparatively discuss relevant findings from other parasitology fields where tissue tropism has been extensively investigated, and reflect on new questions raised by recent discoveries and their potential impact on clinical treatment and disease control strategies.
Topics: Animals; Host-Parasite Interactions; Humans; Organ Specificity; Tissue Distribution; Tropism; Trypanosoma; Trypanosomiasis
PubMed: 31088251
DOI: 10.1098/rsob.190036 -
Virulence Dec 2020
Topics: Female; Fetus; Humans; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Tropism
PubMed: 32363994
DOI: 10.1080/21505594.2020.1759288 -
Frontiers in Bioscience (Landmark... Oct 2021Oncolytic adenovirus has been applied in cancer therapy because of several advantages such as cost-effective production, high transduction efficiency and low toxicity.... (Review)
Review
Oncolytic adenovirus has been applied in cancer therapy because of several advantages such as cost-effective production, high transduction efficiency and low toxicity. Recent efforts have been focused on the modification of oncolytic adenovirus by encoding transgenes within the viral genome to efficiently and selectively replicate within cancer cells, destroy cancerous cells, induce tumor cell apoptosis, and stimulate the recruitment of immune cells to the tumor site. Nevertheless, there are still big challenges for translational research of oncolytic virotherapy in clinical cancer management. Therefore, here we summarize current status on the design and application of oncolytic adenovirus vectors for prostate cancer therapy. In particular, we describe the main receptors associated with the tropism and transduction of oncolytic adenovirus vectors, and propose new directions in future studies for prostate cancer virotherapy.
Topics: Adenoviridae; Cell Line, Tumor; Genetic Vectors; Humans; Male; Oncolytic Virotherapy; Oncolytic Viruses; Prostatic Neoplasms; Tropism
PubMed: 34719211
DOI: 10.52586/4993 -
Cell Reports Mar 2022Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) may alter viral host tropism and affect the activities...
Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) may alter viral host tropism and affect the activities of neutralizing antibodies. Here, we investigated 153 RBD mutants and 11 globally circulating variants of concern (VOCs) and variants of interest (VOIs) (including Omicron) for their antigenic changes and cross-species tropism in cells expressing 18 ACE2 orthologs. Several RBD mutations strengthened viral infectivity in cells expressing ACE2 orthologs of non-human animals, particularly those less susceptible to the ancestral strain. The mutations surrounding amino acids (aas) 439-448 and aa 484 are more likely to cause neutralization resistance. Strikingly, enhanced cross-species infection potential in the mouse and ferret, instead of the neutralization-escape scores of the mutations, account for the positive correlation with the cumulative prevalence of mutations in humans. These findings present insights for potential drivers of circulating SARS-CoV-2 variants and provide informative parameters for tracking and forecasting spreading mutations.
Topics: Animals; COVID-19; Ferrets; Humans; Membrane Glycoproteins; Mice; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Tropism; Viral Envelope Proteins
PubMed: 35303476
DOI: 10.1016/j.celrep.2022.110558 -
Fungal Genetics and Biology : FG & B Sep 2017Fungi, like other organisms, actively sense the environmental light conditions in order to drive adaptive responses, including protective mechanisms against the... (Review)
Review
Fungi, like other organisms, actively sense the environmental light conditions in order to drive adaptive responses, including protective mechanisms against the light-associated stresses, and to regulate development. Ecological niches are characterized by different light regimes, for instance light is absent underground, and light spectra from the sunlight are changed underwater or under the canopy of foliage due to the absorption of distinct wavelengths by bacterial, algal and plant pigments. Considering the fact that fungi have evolved to adapt to their habitats, the complexities of their 'visual' systems may vary significantly. Fungi that are pathogenic on plants experience a special light regime because the host always seeks the optimum light conditions for photosynthesis - and the pathogen has to cope with this environment. When the pathogen lives under the canopy and is indirectly exposed to sunlight, it is confronted with an altered light spectrum enriched for green and far-red light. Botrytis cinerea, the gray mold fungus, is an aggressive plant pathogen mainly infecting the above-ground parts of the plant. As outlined in this review, the Leotiomycete maintains a highly sophisticated light signaling machinery, integrating (near)-UV, blue, green, red and far-red light signals by use of at least eleven potential photoreceptors to trigger a variety of responses, i.e. protection (pigmentation, enzymatic systems), morphogenesis (conidiation, apothecial development), entrainment of a circadian clock, and positive and negative tropism of multicellular (conidiophores, apothecia) and unicellular structures (conidial germ tubes). In that sense, 'looking through the eyes' of this plant pathogen will expand our knowledge of fungal photobiology.
Topics: Botrytis; Circadian Clocks; Cryptochromes; Light; Photoreceptors, Microbial; Phototropism; Plant Components, Aerial; Signal Transduction; Virulence
PubMed: 28648816
DOI: 10.1016/j.fgb.2017.06.002 -
The New Phytologist Sep 2021Characterising the processes that control auxin dynamics is essential to understanding how auxin regulates plant development. Over recent years, several studies have... (Review)
Review
Characterising the processes that control auxin dynamics is essential to understanding how auxin regulates plant development. Over recent years, several studies have investigated auxin diffusion through plasmodesmata, characterising this cell-to-cell diffusion and demonstrating that it affects auxin distributions. Furthermore, studies have shown that plasmodesmatal auxin diffusion affects developmental processes, including phototropism, lateral root emergence and leaf hyponasty. This short Tansley Insight review describes how these studies have contributed to our understanding of auxin dynamics and discusses potential future directions in this area.
Topics: Gene Expression Regulation, Plant; Indoleacetic Acids; Phototropism; Plant Development; Plant Roots; Plasmodesmata
PubMed: 34053083
DOI: 10.1111/nph.17517 -
PLoS Pathogens May 2023Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT...
Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans we show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral ground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple organs in pangolins, with the lungs the major target, and histological expression data revealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome analysis indicated that virus-positive pangolins were likely to have inadequate interferon responses, with relative greater cytokine and chemokine activity in the lung and spleen. Notably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing initial evidence for vertical virus transmission. In sum, our study outlines the biological framework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in humans.
Topics: Animals; Humans; Pangolins; COVID-19; SARS-CoV-2; Virulence; Chiroptera; Phylogeny; RNA, Viral; Tropism
PubMed: 37196026
DOI: 10.1371/journal.ppat.1011384 -
Viruses Mar 2022Although the respiratory tract is the main target of SARS-CoV-2, other tissues and organs are permissive to the infection. In this report, we investigated this...
Although the respiratory tract is the main target of SARS-CoV-2, other tissues and organs are permissive to the infection. In this report, we investigated this wide-spectrum tropism by studying the SARS-CoV-2 genetic intra-host variability in multiple tissues. The virological and histological investigation of multiple specimens from a post-mortem COVID-19 patient was performed. SARS-CoV-2 genome was detected in several tissues, including the lower respiratory system, cardio-vascular biopsies, stomach, pancreas, adrenal gland, mediastinal ganglion and testicles. Subgenomic RNA transcripts were also detected, in favor of an active viral replication, especially in testicles. Ultra-deep sequencing allowed us to highlight several SARS-CoV-2 mutations according to tissue distribution. More specifically, mutations of the spike protein, i.e., V341A (18.3%), E654 (44%) and H655R (30.8%), were detected in the inferior vena cava. SARS-CoV-2 variability can contribute to heterogeneous distributions of viral quasispecies, which may affect the COVID-19 pathogeny.
Topics: COVID-19; Humans; SARS-CoV-2; Tropism; Virus Replication
PubMed: 35336922
DOI: 10.3390/v14030515