-
Viruses Oct 2022Bovine viral diarrhea virus (BVDV) is one of the most hazardous viruses, which causes huge economic losses in the cattle industry around the world. In recent years,... (Review)
Review
Bovine viral diarrhea virus (BVDV) is one of the most hazardous viruses, which causes huge economic losses in the cattle industry around the world. In recent years, there has been a continuous increase in the diversity of pestivirus worldwide. As a member of the genus in the family, BVDV has a wide range of host animals including cattle, goat, sheep, pig, camel and other cloven-hoofed animals, and it has multi-tissue tropism as well. The recognition of their permissive cells by viruses via interaction with the cellular receptors is a prerequisite for successful infection. So far, little is known about the cellular receptors essential for BVDV entry and their detailed functions during BVDV infection. Thus, discovery of the cellular receptors involved in the entry of BVDV and other pestiviruses is significant for development of the novel intervention. The viral envelope glycoprotein E and E2 are crucial determinants of the cellular tropism of BVDV. The cellular proteins bound with E and E2 potentially participate in BVDV entry, and their abundance might determine the cellular tropism of BVDV. Here, we summarize current knowledge regarding the cellular molecules have been described for BVDV entry, such as, complement regulatory protein 46 (CD46), heparan sulfate (HS), the low-density lipoprotein (LDL) receptor, and a disintegrin and metalloproteinase 17 (ADAM17). Furthermore, we focus on their implications of the recently identified cellular receptors for pestiviruses in BVDV life cycle. This knowledge provides a theoretical basis for BVDV prevention and treatment by targeting the cellular receptors essential for BVDV infection.
Topics: Cattle; Animals; Swine; Sheep; Viral Envelope Proteins; Disintegrins; Diarrhea Viruses, Bovine Viral; Diarrhea Virus 1, Bovine Viral; Pestivirus; Receptors, Cell Surface; Heparitin Sulfate; Lipoproteins, LDL; Metalloproteases; Tropism
PubMed: 36298858
DOI: 10.3390/v14102302 -
Molecular Therapy : the Journal of the... Dec 2022AAV vectors are promising delivery tools for human gene therapy. However, broad tissue tropism and pre-existing immunity against natural serotypes limit their clinical...
AAV vectors are promising delivery tools for human gene therapy. However, broad tissue tropism and pre-existing immunity against natural serotypes limit their clinical use. We identified two AAV capsid variants, AAV2-THGTPAD and AAV2-NLPGSGD, by in vivo AAV2 peptide display library screening in a murine model of pressure overload-induced cardiac hypertrophy. Both variants showed significantly improved efficacy in in vivo cardiomyocyte transduction compared with the parental serotype AAV2 as indicated by a higher number of AAV vector episomes in the nucleus and significant improved transduction efficiency. Both variants also outcompeted the reference serotype AAV9 regarding cardiomyocyte tropism, reaching comparable cardiac transduction efficiencies accompanied with liver de-targeting and decreased transduction efficiency of non-cardiac cells. Capsid modification influenced immunogenicity as sera of mice treated with AAV2-THGTPAD and AAV2-NLPGSGD demonstrated a poor neutralization capacity for the parental serotype and the novel variants. In a therapeutic setting, using the long non-coding RNA H19 in low vector dose conditions, novel AAV variants mediated superior anti-hypertrophic effects and revealed a further improved target-to-noise ratio, i.e., cardiomyocyte tropism. In conclusion, AAV2-THGTPAD and AAV2-NLPGSGD are promising novel tools for cardiac-directed gene therapy outperforming AAV9 regarding the specificity and therapeutic efficiency of in vivo cardiomyocyte transduction.
Topics: Animals; Humans; Mice; RNA, Long Noncoding; Myocytes, Cardiac; Tropism; Capsid
PubMed: 35810332
DOI: 10.1016/j.ymthe.2022.07.003 -
Viruses Jul 2022Human papillomaviruses (HPV) are small non-enveloped DNA tumor viruses established as the primary etiological agent for the development of cervical cancer. Decades of... (Review)
Review
Human papillomaviruses (HPV) are small non-enveloped DNA tumor viruses established as the primary etiological agent for the development of cervical cancer. Decades of research have elucidated HPV's primary attachment factor to be heparan sulfate proteoglycans (HSPG). Importantly, wounding and exposure of the epithelial basement membrane was found to be pivotal for efficient attachment and infection of HPV in vivo. Sulfation patterns on HSPG's become modified at the site of wounds as they serve an important role promoting tissue healing, cell proliferation and neovascularization and it is these modifications recognized by HPV. Analogous HSPG modification patterns can be found on tumor cells as they too require the aforementioned processes to grow and metastasize. Although targeting tumor associated HSPG is not a novel concept, the use of HPV to target and treat tumors has only been realized in recent years. The work herein describes how decades of basic HPV research has culminated in the rational design of an HPV-based virus-like infrared light activated dye conjugate for the treatment of choroidal melanoma.
Topics: Alphapapillomavirus; Heparan Sulfate Proteoglycans; Heparitin Sulfate; Humans; Papillomaviridae; Papillomavirus Infections; Tropism; Uveal Neoplasms
PubMed: 36016277
DOI: 10.3390/v14081656 -
Current Opinion in Plant Biology Feb 2018While fast plant movements are spectacular but rare, almost all plants exhibit relatively slow, growth-mediated tropic movements that are key to their survival in the... (Review)
Review
While fast plant movements are spectacular but rare, almost all plants exhibit relatively slow, growth-mediated tropic movements that are key to their survival in the natural world. In this brief review, we discuss recent insights into the molecular mechanisms underlying phototropism, gravitropism, hydrotropism, and autostraightening. Careful molecular genetic and physiological studies have helped confirm the importance of lateral auxin gradients in gravitropic and phototropic responses. However, auxin signaling does not explain all tropisms: recent work has shown that abscisic acid signaling mediates root hydrotropism and has implicated mechanosensing in autostraightening, the organ straightening process recently modeled as a proprioceptive response. The interactions between distinct tropic signaling pathways and other internal and external sensory processes are also now being untangled.
Topics: Gravitropism; Light; Phototropism; Plant Development; Plant Physiological Phenomena; Plant Roots; Plants; Signal Transduction; Tropism
PubMed: 29107827
DOI: 10.1016/j.pbi.2017.10.003 -
European Journal of Medical Research Dec 2021Vertebral rotation and facet tropism are very common in various lumbar degenerative diseases. Facet tropism means the presence of asymmetric angles on both sides of the...
BACKGROUND
Vertebral rotation and facet tropism are very common in various lumbar degenerative diseases. Facet tropism means the presence of asymmetric angles on both sides of the facet joints. Studies have shown that facet tropism contributes to lumbar degenerative disease, and also inevitably leads to the asymmetry of movement and the imbalance of force, which may be possible to rotate the vertebral body. The aim of this study was to explore the correlation between lumbar vertebral rotation and facet tropism in patients with lumbar degenerative diseases.
METHODS
A total of 198 patients with lumbar degenerative diseases from 2018 to 2019 were enrolled. Five hundred and seventy vertebral rotation angles and 1140 facet angles were measured. The vertebral bodies are divided into non-rotation group (Group A) and rotation group (Group B) with the vertebral rotation angle of 3° as the boundary. The information including gender, age, BMI (body mass index), bone mineral density, history of smoking, drinking, hypertension, diabetes, diagnosis, segment distribution, and degree of facet degeneration were also counted. Using inter-class correlation coefficients (ICC) to test the reliability of measurement results. Univariate and multivariate logistic regression analysis were used to analyze the relationship between vertebral rotation and facet tropism.
RESULTS
The consistency of the ICC within the groups of the observers is above 0.8, with good agreement. The results of univariate analysis showed that facet tropism was significantly different between group A and group B (OR (odds ratio) = 3.30, 95% CI = 2.03-5.35, P < 0.0001). Other significant factors were included as adjustment variables into the multivariate regression model. Three models were analyzed separately (Model 1: non-adjusted. Model 2: adjust for age; facet degeneration; Model 3: adjust for age; disease distribution; segment distribution; facet degeneration). The results showed that after adjusting the confounders, the correlation between facet tropism and vertebral rotation did not change (Model 1: OR = 3.30, 95% CI = 2.03-5.35, P < 0.0001; Model 2: adjusted OR = 2.87, 95% CI = 1.66-4.97, P = 0.0002, Model 3: adjusted OR = 2.84, 95% CI = 1.56-5.17, P = 0.0006).
CONCLUSION
Current research demonstrates that there is an association between vertebral rotation and facet tropism, suggesting that vertebral rotation may also have a certain degree of correlation with lumbar degenerative diseases.
Topics: Body Mass Index; Female; Follow-Up Studies; Humans; Intervertebral Disc Degeneration; Lumbar Vertebrae; Male; Middle Aged; Retrospective Studies; Tomography, X-Ray Computed; Tropism
PubMed: 34930499
DOI: 10.1186/s40001-021-00622-7 -
American Journal of Botany Jan 2013While water shortage remains the single-most important factor influencing world agriculture, there are very few studies on how plants grow in response to water... (Review)
Review
While water shortage remains the single-most important factor influencing world agriculture, there are very few studies on how plants grow in response to water potential, i.e., hydrotropism. Terrestrial plant roots dwell in the soil, and their ability to grow and explore underground requires many sensors for stimuli such as gravity, humidity gradients, light, mechanical stimulations, temperature, and oxygen. To date, extremely limited information is available on the components of such sensors; however, all of these stimuli are sensed in the root cap. Directional growth of roots is controlled by gravity, which is fixed in direction and intensity. However, other environmental factors, such as water potential gradients, which fluctuate in time, space, direction, and intensity, can act as a signal for modifying the direction of root growth accordingly. Hydrotropism may help roots to obtain water from the soil and at the same time may participate in the establishment of the root system. Current genetic analysis of hydrotropism in Arabidopsis has offered new players, mainly AHR1, NHR1, MIZ1, and MIZ2, which seem to modulate how root caps sense and choose to respond hydrotropically as opposed to other tropic responses. Here we review the mechanism(s) by which these genes and the plant hormones abscisic acid and cytokinins coordinate hydrotropism to counteract the tropic responses to gravitational field, light or touch stimuli. The biological consequence of hydrotropism is also discussed in relation to water stress avoidance.
Topics: Arabidopsis; Models, Biological; Plant Roots; Tropism; Water
PubMed: 23258371
DOI: 10.3732/ajb.1200306 -
Molecular Oral Microbiology Dec 2022A detailed understanding of where bacteria localize is necessary to advance microbial ecology and microbiome-based therapeutics. The site-specialist hypothesis predicts...
A detailed understanding of where bacteria localize is necessary to advance microbial ecology and microbiome-based therapeutics. The site-specialist hypothesis predicts that most microbes in the human oral cavity have a primary habitat type within the mouth where they are most abundant. We asked whether this hypothesis accurately describes the distribution of the members of the genus Streptococcus, a clinically relevant taxon that dominates most oral sites. Prior analysis of 16S rRNA gene sequencing data indicated that some oral Streptococcus clades are site-specialists while others may be generalists. However, within complex microbial populations composed of numerous closely related species and strains, such as the oral streptococci, genome-scale analysis is necessary to provide the resolution to discriminate closely related taxa with distinct functional roles. Here, we assess whether individual species within this genus are specialists using publicly available genomic sequence data that provide species-level resolution. We chose a set of high-quality representative genomes for human oral Streptococcus species. Onto these genomes, we mapped shotgun metagenomic sequencing reads from supragingival plaque, tongue dorsum, and other sites in the oral cavity. We found that every abundant Streptococcus species in the healthy human oral cavity showed strong site-tropism and that even closely related species such as S. mitis, S. oralis, and S. infantis specialized in different sites. These findings indicate that closely related bacteria can have distinct habitat distributions in the absence of dispersal limitation and under similar environmental conditions and immune regimes. Substantial overlap between the core genes of these three species suggests that site-specialization is determined by subtle differences in genomic content.
Topics: Humans; RNA, Ribosomal, 16S; Streptococcus; Microbiota; Metagenome; Bacteria; Mouth; Tropism; Phylogeny
PubMed: 36073311
DOI: 10.1111/omi.12387 -
Viruses Jan 2022Oncolytic herpes simplex virus (oHSV) is a highly promising treatment for solid tumors. Intense research and development efforts have led to first-in-class approval for... (Review)
Review
Oncolytic herpes simplex virus (oHSV) is a highly promising treatment for solid tumors. Intense research and development efforts have led to first-in-class approval for an oHSV for melanoma, but barriers to this promising therapy still exist that limit efficacy. The process of infection, replication and transmission of oHSV in solid tumors is key to obtaining a good lytic destruction of infected cancer cells to kill tumor cells and release tumor antigens that can prime anti-tumor efficacy. Intracellular tumor cell signaling and tumor stromal cells present multiple barriers that resist oHSV activity. Here, we provide a review focused on oncolytic HSV and the essential viral genes that allow for virus replication and spread in order to gain insight into how manipulation of these pathways can be exploited to potentiate oHSV infection and replication among tumor cells.
Topics: Animals; Cell Line, Tumor; Herpes Simplex; Herpesvirus 1, Human; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Tropism; Virus Replication
PubMed: 35062322
DOI: 10.3390/v14010118 -
Nature Metabolism Mar 2022Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae. Severe acute respiratory...
Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart and kidney. Whether it also directly affects the liver has been debated. Here we provide clinical, histopathological, molecular and bioinformatic evidence for the hepatic tropism of SARS-CoV-2. We find that liver injury, indicated by a high frequency of abnormal liver function tests, is a common clinical feature of COVID-19 in two independent cohorts of patients with COVID-19 requiring hospitalization. Using autopsy samples obtained from a third patient cohort, we provide multiple levels of evidence for SARS-CoV-2 liver tropism, including viral RNA detection in 69% of autopsy liver specimens, and successful isolation of infectious SARS-CoV-2 from liver tissue postmortem. Furthermore, we identify transcription-, proteomic- and transcription factor-based activity profiles in hepatic autopsy samples, revealing similarities to the signatures associated with multiple other viral infections of the human liver. Together, we provide a comprehensive multimodal analysis of SARS-CoV-2 liver tropism, which increases our understanding of the molecular consequences of severe COVID-19 and could be useful for the identification of organ-specific pharmacological targets.
Topics: COVID-19; Humans; Liver; Proteomics; SARS-CoV-2; Tropism
PubMed: 35347318
DOI: 10.1038/s42255-022-00552-6 -
Comparative Medicine Dec 2021Murine astrovirus 2 (MuAstV2) is a novel murine astrovirus recently identified in laboratory and wild mice. MuAstV2 readily transmits between immunocompetent mice yet...
Murine astrovirus 2 (MuAstV2) is a novel murine astrovirus recently identified in laboratory and wild mice. MuAstV2 readily transmits between immunocompetent mice yet fails to transmit to highly immunocompromised mouse strains-a unique characteristic when contrasted with other murine viruses including other astroviruses. We characterized the viral shedding kinetics and tissue tropism of MuAstV2 in immunocompetent C57BL/6NCrl mice and evaluated the apparent resistance of highly immunocompromised NOD- /NjuCrl mice to MuAstV2 after oral inoculation. Temporal patterns of viral shedding were determined by serially measuring fecal viral RNA. Tissue tropism and viral load were characterized and quantified by using in-situ hybridization (ISH) targeting viral RNA. Cellular tropism was characterized by evaluating fluorescent colocalization of viral ISH with various immunohistochemical markers. We found a rapid increase of fecal viral RNA in B6 mice, which peaked at 5 d after inoculation (dpi) followed by cessation of shedding by 168 dpi. The small intestine had the highest percentage of hybridization (3.09% of tissue area) of all tissues in which hybridization occurred at 5 dpi. The thymus displayed the next highest degree of hybridization (2.3%) at 7 dpi, indicating extraintestinal viral spread. MuAstV2 RNA hybridization was found to colocalize with only 3 of the markers evaluated: CD3 (T cells), Iba1 (macrophages), and cytokeratin (enterocytes). A higher percentage of CD3 cells and Iba1 cells hybridized with MuAstV2 as compared with cytokeratin at 2 dpi (CD3, 59%; Iba1, 46%; cytokeratin, 6%) and 35 dpi (CD3, 14%; Iba1, 55%; cytokeratin, 3%). Neither fecal viral RNA nor viral hybridization was noted in NCG mice at the time points examined. In addition, mice of mixed genetic background were inoculated, and only those with a functioning gene shed MuAstV2. Results from this study suggest that infection of, or interaction with, the immune system is required for infection by or replication of MuAstV2.
Topics: Animals; Astroviridae; Biology; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Tropism
PubMed: 34794533
DOI: 10.30802/AALAS-CM-21-000039