Host Tissue Tropism Research Articles

A Comprehensive Review of COVID-19 Transmission and Vaccine Development: Past, Present, and Future Prospects

Corona virusis a large group of viruses that cause respiratory and gastrointestinal illnesses. Originating in Wuhan, China, in December 2019, the 2019-novel Corona virus pandemic has spread around the globe and raised concerns. Due to the large number of individuals affected worldwide, the illness has rendered isolated areas uninhabitable, forcing residents to stay inside their homes in an effort to contain its spread. The 2019 corona virus, the severe acute respiratory syndrome corona virus, and the first human pandemic of the twenty-first century have identical human cellular receptors. Nevertheless, compared to the severe acute respiratory syndrome corona virus, the 2019-novel corona virus is more powerful, highly infectious, and changeable. The spike glycoprotein is the best place to create a 2019 corona virus vaccine. Where would be best to develop a vaccine against the 2019 novel Numerous mechanisms, including receptor binding, membrane fusion via conformational changes, viral internalization, host tissue tropism, and spike deactivation due to antibody-induced instability, depend on the spike glycoprotein known as corona virus. After the first breakout in December 2019, everyone in the world felt momentarily comforted when the death ratio began to decline around the end of 2020. People believed that the summer was one of the best seasons to combat illness and prevent its spread. However, in recent months, a global outcry over new 2019 Corona virus infection variations has garnered attention, putting people's lives, regardless of age or community, at risk. Scholars must concentrate on the findings and advancements. In addition, we have worked to increase awareness of the need for the creation of an international virtual community in order to enable smooth communication across all parts of the world and support mankind in the case of a category 5 coronavirus outbreak.

Description, life cycle, and development of the myxozoan Myxobolus rasmusseni n. sp. in fathead minnows, Pimephales promelas: A possible emerging pathogen in southern Alberta, Canada

Morphological, gene sequence, host tissue tropism, and life cycle characteristics were utilized to describe the myxozoan, Myxobolus rasmusseni n. sp. from fathead minnow, Pimephales promelas, collected from reservoirs in southern Alberta. Results from serial histological sections of whole heads showed that myxospores were contained within irregular-shaped and sized coelozoic capsules (=plasmodia). Clusters of membrane-bound, myxospore-filled plasmodia filled the head cavities of juvenile fathead minnows, leading to the development of large, white, disfiguring lesions in mid to late summer. Bilateral exopthalmia (pop-eye disease) was a common outcome of M. rasmusseni n. sp. development. BLASTn search of a 1974 bp sequence of the 18S rDNA gene isolated from myxospores indicated that M. rasmusseni n. sp. was distinct from other coelozoic and histozoic Myxobolus spp. cataloged in GenBank. 18S rDNA gene sequences from triactinomyxon spores released from the oligochaete Tubifex were 100% identical to sequences from myxospores collected from syntopic fathead minnows. Results from a longitudinal survey of the 2020 cohort of fathead minnows showed that young-of-the-year are exposed at 1–5 mo and that 60–90% of these had developed myxospore-filled lesions approximately one year later. Data regarding potential sources and timing of M. rasmusseni n. sp. emergence in fathead minnow populations are needed.

Co-infecting Haemoproteus species (Haemosporida, Apicomplexa) show different host tissue tropism during exo-erythrocytic development in Fringilla coelebs (Fringillidae)

Avian haemosporidians of the genera Plasmodium, Haemoproteus, and Leucocytozoon are common blood parasites in wild birds all over the world. Despite their importance as pathogens potentially compromising host fitness and health, little is known about the exo-erythrocytic development of these parasites, particularly during co-infections which predominate in wildlife. This study aimed to address this issue using Haemoproteus parasites of Fringilla coelebs, a common bird species of the Western Palearctic and host to a variety of haemosporidian parasite lineages. Blood and tissue samples of 20 F. coelebs, positive for haemosporidians by blood film microscopy, were analysed by PCR and sequencing to determine cytochrome b lineages of the parasites. Tissue sections were examined for exo-erythrocytic stages by histology and in situ hybridization applying genus-, species-, and lineage-specific probes which target the 18S rRNA of the parasites. In addition, laser microdissection of tissue stages was performed to identify parasite lineages. Combined molecular results of PCR, laser microdissection, and in situ hybridization showed a high rate of co-infections, with Haemoproteus lineages dominating. Exo-erythrocytic meronts of five Haemoproteus spp. were described for the first known time, including Haemoproteus magnus hCCF6, Haemoproteus fringillae hCCF3, Haemoproteus majoris hCCF5, Haemoproteus sp. hROFI1, and Haemoproteus sp. hCCF2. Merogonic stages were observed in the vascular system, presenting a formerly unknown mode of exo-erythrocytic development in Haemoproteus parasites. Meronts and megalomeronts of these species were distinct regarding their morphology and organ distribution, indicating species-specific patterns of merogony and different host tissue tropism. New pathological aspects of haemoproteosis were reported. Furthermore, phylogenetic analysis of Haemoproteus spp. with regard to their exo-erythrocytic stages points towards separation of non-megalomeront-forming species from megalomeront-forming species, calling for further studies on exo-erythrocytic development of haemosporidian parasites to explore the phylogenetic character of this trait.

Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV).

The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools. The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server. Antigenicity was predicted by NetCTL 1.2 and validated by IEDB Analysis Resource server. The structural divergence was determined by using SuperPose Version 1.0 based on cryo-EM structure of the SARS coronavirus spike glycoprotein. Our data suggests that 2019-nCoV is newly spilled coronavirus into humans in China is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV. Addition of a novel glycosylation sites were observed in 2019-nCoV. In addition, antigenic analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. In spite of the variation in S protein amino acid composition, we found no significant difference in their structures. Collectively, for the first time our results exhibit the emergence of human 2019-nCoV is closely related to predecessor SARS-CoV and provide the evidence that 2019-nCoV uses various novel glycosylation sites as SARS-CoV and may have a potential to become pandemic owing its antigenic discrepancy. Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV.

Myxobolus linzhiensis n. sp. (Myxozoa: Myxobolidae) from the gill filament of Schizothorax oconnori Lloyd (Cyprinidae: Schizothoracinae) in Tibet, China: morphological and molecular characterization.

In this report, a new myxosporean species, Myxobolus linzhiensis n. sp. (Cnidaria: Myxozoa: Bivalvulida), was described from the endemic cyprinid Schizothorax oconnori inhabiting the Yarlung Tsangpo River in the Tibetan plateau, China. The whitish ellipsoidal plasmodia of M. linzhiensis n. sp. grew under the epithelium of gill filaments, 1.7-mm long and 0.4-mm wide, and were found in the 3 of 8 examined S. oconnori (37.5%). Mature spores appeared suborbicular in frontal view, fusiform shaped in lateral view with tapering anterior, measuring 11.4±0.7 (10.1-13.0) μm in length, 10.6±0.4 (10.0-11.3) μm in width, and 6.6±0.3 (6.2-7.0) μm in thickness. Two equal polar capsules were pyriform with an apophysis at its top end, measuring 5.7±0.5 (4.8-6.7) μm in length, 3.8±0.2 (3.2-4.2) μm in width, and polar filaments coiled 4 turns. Spore valves were symmetrical, and sutural ridge was straight and thin, running near the middle of the valves. Although Myxobolus linzhiensis n. sp. showed similar morphological characteristics with Myxobolus chushi Dar Kaur & Chishti 2017 from Schizothorax niger, Myxobolus kienweiensis Ma, 1976 from Schizothorax davidi, the new myxosporean was distinguished with them in spore shape, polar filament, and host-tissue tropism. Homology search by BLAST in GenBank indicated that the obtained 18S rDNA sequence of M. linzhiensis n. sp. (KY965935) did not match any available myxozoan sequence, most similar to Henneguya zikaweiensis, and showing less than 93% sequence similarity. Phylogenetical analyses demonstrated that M. linzhiensis n. sp. was firmly clustered in the clade consisting of myxosporeans Thelohanellus, Myxobolus, Henneguya from Asian cyprinids. This study is the first report on myxosporean parasitizing in endemic fish in the Tibetan Plateau, China.

Evolution of Newcastle Disease Virus Quasispecies Diversity and Enhanced Virulence after Passage through Chicken Air Sacs.

It has been reported that lentogenic Newcastle disease virus (NDV) isolates have the potential to become velogenic after their transmission and circulation in chickens, but the underlying mechanism is unclear. In this study, a highly velogenic NDV variant, JS10-A10, was generated from the duck-origin lentogenic isolate JS10 through 10 consecutive passages in chicken air sacs. The velogenic properties of this selected variant were determined using mean death time (MDT) assays, intracerebral pathogenicity index (ICPI), the intravenous pathogenicity index (IVPI), histopathology, and the analysis of host tissue tropism. In contrast, JS10 remained lentogenic after 20 serial passages in chicken eggs (JS10-E20). The JS10, JS10-A10, and JS10-E20 genomes were sequenced and found to be nearly identical, suggesting that both JS10-A10 and JS10-E20 were directly generated from JS10. To investigate the mechanism for virulence enhancement, the partial genome covering the F0 cleavage site of JS10 and its variants were analyzed using ultradeep pyrosequencing (UDPS) and the proportions of virulence-related genomes in the quasispecies were calculated. Velogenic NDV genomes accumulated as a function of JS10 passaging through chicken air sacs. Our data suggest that lentogenic NDV strains circulating among poultry might be a risk factor to future potential velogenic NDV outbreaks in chickens. An avirulent isolate, JS10, was passaged through chicken air sacs and embryos, and the pathogenicity of the variants was assessed. A virulent variant, JS10-A10, was generated from consecutive passage in air sacs. We developed a deep-sequencing approach to detect low-frequency viral variants across the NDV genome. We observed that virulence enhancement of JS10 was due to the selective accumulation of velogenic quasispecies and the concomitant disappearance of lentogenic quasispecies. Our results suggest that because it is difficult to avoid contact between natural waterfowl reservoirs and sensitive poultry operations, circulating lentogenic NDV strains may represent a potential reservoir for emergent velogenic NDV strains that could cause outbreaks in chickens.

The Role of Sialyl Glycan Recognition in Host Tissue Tropism of the Avian Parasite Eimeria tenella

Eimeria spp. are a highly successful group of intracellular protozoan parasites that develop within intestinal epithelial cells of poultry, causing coccidiosis. As a result of resistance against anticoccidial drugs and the expense of manufacturing live vaccines, it is necessary to understand the relationship between Eimeria and its host more deeply, with a view to developing recombinant vaccines. Eimeria possesses a family of microneme lectins (MICs) that contain microneme adhesive repeat regions (MARR). We show that the major MARR protein from Eimeria tenella, EtMIC3, is deployed at the parasite-host interface during the early stages of invasion. EtMIC3 consists of seven tandem MAR1-type domains, which possess a high specificity for sialylated glycans as shown by cell-based assays and carbohydrate microarray analyses. The restricted tissue staining pattern observed for EtMIC3 in the chicken caecal epithelium indicates that EtMIC3 contributes to guiding the parasite to the site of invasion in the chicken gut. The microarray analyses also reveal a lack of recognition of glycan sequences terminating in the N-glycolyl form of sialic acid by EtMIC3. Thus the parasite is well adapted to the avian host which lacks N-glycolyl neuraminic acid. We provide new structural insight into the MAR1 family of domains and reveal the atomic resolution basis for the sialic acid-based carbohydrate recognition. Finally, a preliminary chicken immunization trial provides evidence that recombinant EtMIC3 protein and EtMIC3 DNA are effective vaccine candidates.

Campylobacter jejuni Host Tissue Tropism: A Consequence of Its Low-Carb Lifestyle?

Mechanisms underlying virulence properties of Campylobacter jejuni have historically been difficult to identify. In this issue of Cell Host & Microbe, Hofreuter et al. (2008) show that C. jejuni's ability to metabolize glutamine, glutathione, and asparagine affects its ability to colonize specific host tissues. These findings reflect the emerging theme of bacterial physiology directly impacting pathogenesis.

Yersinia enterocolitica isolates of differing biotypes from humans and animals are adherent, invasive and persist in macrophages, but differ in cytokine secretion profiles in vitro

Previous epidemiological studies have demonstrated a potential link between the serotypes of Yersinia enterocolitica recovered from cattle, sheep and pigs and those isolated from human disease cases. Further studies utilizing amplified fragment length polymorphisms have shown a relationship at the genetic level between strains of biotypes 3 and 4 from humans and livestock, and also suggested that some biotype 1A isolates, classically defined as non-pathogenic, are closely related to biotype 3 and 4 isolates. This study sought to understand further the pathogenic potential of Y. enterocolitica isolates from livestock in Great Britain. A range of surrogate in vitro models, such as invasion of epithelial tissue cultures, survival in cultured macrophages and cytokine secretion response, was employed to assess the pathogenicity of 88 strains. The results suggested that all isolates examined were capable of adhering to and invading epithelial cells and of surviving within macrophages. However, the inflammatory response of the infected macrophages differed with the infecting Y. enterocolitica subtype, with the response to pathogenic biotype 3 and 4 isolates different to that observed with biotype 1A isolates, and with the biotype 3 O : 5,27 isolates recovered exclusively from animals. Infections of porcine tissue also suggested the possibility of host-tissue tropism within Y. enterocolitica subtypes.

Host cell tropism underlies species restriction of human and bovine Cryptosporidium parvum genotypes.

It has been recognized recently that human cryptosporidiosis is usually caused by Cryptosporidium parvum genotype I ("human" C. parvum), which is not found in animals. Compared to C. parvum genotype II, little is known of the biology of invasion of the human-restricted C. parvum genotype I. The aims of the present study were (i) to explore and compare with genotype II the pathogenesis of C. parvum genotype I infection by using an established in vitro model of infection and (ii) to examine the possibility that host-specific cell tropism determines species restriction among C. parvum genotypes by using a novel ex vivo small intestinal primary cell model of infection. Oocysts of C. parvum genotypes I and II were used to infect HCT-8 cells and primary intestinal epithelial cells in vitro. Primary cells were harvested from human endoscopic small-bowel biopsies and from bovine duodenum postmortem. C. parvum genotype I infected HCT-8 cells with lower efficiency than C. parvum genotype II. Actin colocalization at the host parasite interface and reduction in levels of invasion after treatment with microfilament inhibitors (cytochalasin B and cytochalasin D) were observed for both genotypes. C. parvum genotype II invaded primary intestinal epithelial cells, regardless of the species of origin. In contrast, C. parvum genotype I invaded only human small-bowel cells. The pathogenesis of C. parvum genotype I differs from C. parvum genotype II. C parvum genotype I does not enter primary bovine intestinal cells, suggesting that the species restriction of this genotype is due to host tissue tropism of the infecting isolate.

P0561 HOST CELL TROPHISM UNDERLIES SPECIES RESTRICTION OF HUMAN AND BOVINE CRYPTOSPORIDIUM PARVUM GENOTYPES

Introduction: It has been recognised recently that human cryptosporidiosis is usually caused by C. parvum genotype 1 (“human” C. parvum), which is not found in animals. Compared with C. parvum genotype II (cattle C. parvum), little is known of the biology of invasion of human restricted C. parvum genotype I. The aims of this study were (i) to explore and compare with genotype II the pathogenesis of C. parvum genotype I infection using an established in vitro model of infection and (ii) to examine the possibility that host specific cell tropism determines species restriction among C. parvum genotype I and genotype II using a novel ex vivo small intestinal primary cell model of infection. Methods: Oocysts of C. parvum genotype I and genotype II were used to infect HCT-8 cells and primary intestinal epithelial cells in vitro. Primary cells were harvested from human endoscopic small bowel biopsies and from bovine duodenum post mortem. Results: C. parvum genotype I infected HCT-8 cells with lower efficiency than C. parvum genotype II. Actin colocalization at the host parasite interface and reduction in levels of invasion following treatment with microfilament inhibitors (cytochalasin B and cytochalasin D) were observed for both types of C. parvum. Pre-treatment of oocysts with microtubule inhibitors (colchicine and vincristine) reduced the invasion efficiency of genotype II isolates. Primary cells were more efficiently infected than HCT-8 cells by C. parvum genotype I parasites. C. parvum genotype II invaded primary cells, regardless of human or bovine origin. In contrast, C. parvum genotype I invaded only human small bowel cells Conclusion: The pathogenesis of C. parvum genotype I differs from C. parvum genotype II. C. parvum genotype I does not enter primary bovine intestinal cells suggesting that the species restriction of this C. parvum genotype is due to host tissue tropism of the infecting isolate.

Role for a secreted cysteine proteinase in the establishment of host tissue tropism by group A streptococci.

Primary infection of the human host by group A streptococci (GAS) most often involves either the epidermis of the skin or the oropharyngeal mucosa. A humanized in vivo model for impetigo was used to investigate the basis for host tissue tropism among GAS. Disruption of the speB gene (encoding for a secreted cysteine proteinase) led to a loss of virulence for two impetigo-derived strains (M-types 33 and 53), as evidenced by a diminution in tissue damage and a lack of reproductive growth. The level of cysteine proteinase activity in overnight cultures was associated with the extent of gross pathological changes induced by strains displaying varied degrees of virulence in the impetigo model. Moreover, high levels of secreted cysteine proteinase activity correlated with a genetic marker for preferred tissue site of infection at the skin (emm pattern D). The addition of exogenous SpeB to a speB mutant (emm pattern D) or to an avirulent throat-like strain (emm pattern A) led to increased bacterial reproduction at the skin. The data provide both experimental and epidemiological evidence for a critical role of a secreted bacterial protease in promoting host tissue-specific infection.