SEARCH · PubMed Health

Results for “host:pathogen interactions”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 955 records · Page 53Linked to original sources

PubMed2005

Genetic variation in response to an indirect ecological effect.

Indirect ecological effects (IEEs) are widespread and often as strong as the phenotypic effects arising from direct interactions in natural communities. Indirect effects can influence competitive interactions, and are thought to be important selective forces. However, the extent that selection arising from IEEs results in long-term evolutionary change depends on genetic variation underlying the phenotypic response-that is, a genotype-by-IEE interaction. We provide the first data on genetic variation in the response of traits to an IEE, and illustrate how such genetic variation might be detected and analysed. We used a model tri-trophic system to investigate the effect of host plants on two populations of predatory ladybirds through a clonal aphid herbivore. A split-family experimental design allowed us to estimate the effects of aphid host plant on ladybird traits (IEE) and the extent of genetic variation in ladybird predators for response to these effects (genotype-by-indirect environmental effect interaction). We found significant genetic variation in the response of ladybird phenotypes to the indirect effect of host plant of their aphid prey, demonstrating the potential for evolutionary responses to selection arising from the prey host.

Animals↗

PubMed2025

EV-D68 cleaves LARP1 and PABPC1 by 3Cpro to redirect host mRNA translation machinery toward its genomic RNA.

Enterovirus D68 (EV-D68) is an emerging pathogen associated with severe respiratory diseases and neurological complications, such as acute flaccid myelitis. EV-D68 has developed sophisticated mechanisms to hijack host translation machinery, facilitating its replication and impairing host mRNA translation. In this study, we demonstrate that EV-D68 cleaves La-related protein 1 (LARP1) and poly(A)-binding protein cytoplasmic 1 (PABPC1) through its proteases 3Cpro and 2Apro. Our results indicate that overexpressing LARP1 and PABPC1 significantly inhibits EV-D68 replication and reduces the virus-mediated suppression of host translation. While both LARP1 and PABPC1 regulate translation, they exert antiviral effects through distinct mechanisms. We found that LARP1 interacts with the 5'UTR of EV-D68 RNA through its LAM domain, and this interaction is crucial for its antiviral function. LARP1 translation modulation is also influenced by the mTOR and CDK1 signaling pathways. Viral infection inhibits mTOR and CDK1 phosphorylation, which enhances LARP1's binding to viral RNA and inhibits viral translation. To counteract this inhibition, EV-D68 cleaves LARP1 through 3Cpro, thereby promoting efficient viral translation. We also investigated other enteroviruses, such as EV-A71 and CV-A16, which similarly target LARP1 and PABPC1, indicating a conserved mechanism across enteroviruses. Our findings offer new insights into how EV-D68 manipulates host translation and highlight the potential of targeting LARP1 and PABPC1 for antiviral interventions.

Humans↗

PubMed2026

Shining Light on Late Blight.

In this retrospective on my journey in science, I shine light on the ins and outs of the late blight pathogen Phytophthora infestans. While studying plant pathology, I became fascinated by the molecular mechanisms that govern the development of cells and organisms and ended up unraveling intimate plant-microbe interactions. I have been fortunate to work in an inspiring environment and with committed coworkers. I am proud of what we achieved as a team. By digging into the biology of Phytophthora and exploring genomes and pathogenicity mechanisms, we uncovered a treasure trove of novelties and peculiarities that offer ample opportunities for designing pathogen-informed control strategies.

Plant Diseases↗

PubMed2024

Identification of interaction partners of outer inflammatory protein A: Computational and experimental insights into how Helicobacter pylori infects host cells.

Outer membrane proteins (OMPs) play a key role in facilitating the survival of Helicobacter pylori within the gastric tissue by mediating adherence. Among these proteins, Outer inflammatory protein A (OipA) is a critical factor in H. pylori colonization of the host gastric epithelial cell surface. While the role of OipA in H. pylori attachment and its association with clinical outcomes have been established, the structural mechanisms underlying OipA's action in adherence to gastric epithelial cells remain limited. Our study employed experimental and computational approaches to investigate the interaction partners of OipA on the gastric epithelial cell surface. Initially, we conducted a proteomic analysis using a pull-down assay with recombinant OipA and gastric epithelial cell membrane proteins to identify the OipA interactome. This analysis revealed 704 unique proteins that interacted with OipA. We subsequently analyzed 16 of these OipA partners using molecular modeling tools. Among these 16 partners, we highlight three human proteins, namely Hepatocyte growth factor (HGF), Mesenchymal epithelial transition factor receptor (Met), and Adhesion G Protein-Coupled Receptor B1 (AGRB1) that could play a role in H. pylori adherence to the gastric epithelial cell surface with OipA. Collectively, these findings reveal novel host interactions mediated by OipA, suggesting their potential as therapeutic targets for combating H. pylori infection.

Helicobacter pylori↗

PubMed1989

Plant viruses: a tool-box for genetic engineering and crop protection.

Traditionally, plant viruses are viewed as harmful, undesirable pathogens. However, their genomes can provide several useful 'designer functions' or 'sequence modules' with which to tailor future gene vectors for plant or general biotechnology. The majority (77%) of known plant viruses have single-stranded RNA of the messenger (protein coding) sense as their genetic material. Over the past 4 years, improved in vitro transcription systems and the construction of partial or full-length DNA copies of several plant RNA viruses have enhanced our ability to manipulate and study their genomes, particularly in the context of their pathogenic interactions with host plants. Recently, two forms of genetically engineered protection against plant virus infections have been reported. In both, a virus-related 'interfering' molecule was stably introduced into plants via the DNA-transfer mechanism of Agrobacterium tumefaciens. To date, the choice of 'interfering' molecule has been guided by empirical field-observations and each is effective against only a narrow range of closely-related viruses. As yet, we do not fully understand the molecular mechanism(s) responsible for the observed protection. The ability to manipulate the plant-pathogen relationship is a powerful tool to increase our knowledge and improve future strategies for unconventional cropprotection by genetic engineering techniques.

Agriculture↗

PubMed1995

Epidemiology of diarrhoea in two major cities in Saudi Arabia.

The epidemiological pattern of diarrhoeal diseases, causative agents and risk factors of their occurrence in two referral hospitals of Saudi Arabia is presented in this study. Stool specimens from 1726 admitted diarrhoeal cases were examined for parasites, yeast, enteropathogenic bacteria and rotavirus using the ELISA test. 41.3% of cases were due to rotavirus (RVGE) while 53.1% of cases showed no causative pathogens. Mean age of all cases was 20.2 months and RVGE cases showed a steady rise from the neonatal period onward, reaching a peak between 6-14 months. Males accounted for higher percentage of all diarrhoeal cases. Mothers of diarrhoea cases were mostly housewives with low educational level. Bottle fed children showed higher proportion (53.1%) of diarrhoea than other types of feeding suggesting the faeco-oral route of infection and the effect of poor sanitation. A pattern of higher RVGE cases was seen in warmer months in Al-taif and in cooler months in Jeddah. Findings demonstrated the interaction between host, pathogen and environmental factors in the epidemiology of infectious diarrhoeas in developing countries and the areas of possible prevention.

Breast Feeding↗

PubMed2025

Proviral functions of HMGB1 in HAdV-C5 replication compartments.

UNLABELLED: Human adenoviruses (HAdVs) induce significant reorganization of the nuclear environment, leading to the formation of virus-induced subnuclear structures known as replication compartments (RCs). Within these RCs, viral genome replication, gene expression, and modulation of cellular antiviral responses are tightly coordinated, making them valuable models for studying virus-host interactions. In a recent study, we analyzed the protein composition of HAdV type 5 (HAdV-C5) RCs isolated from infected primary cells at different time points during infection using quantitative proteomics. We identified several chromatin modifiers, including the high-mobility group box 1 protein (HMGB1) as components associated with RCs and demonstrated that HMGB1 can be relocalized to RCs from different HAdV species, thereby modulating viral replication in a species-specific manner. In the present work, using click-chemistry and proximity ligation assays, we discovered that HMGB1 localizes to sites of DNA replication within RCs and that its interaction with DBP in RCs is dependent on both DNA replication and RC assembly. HMGB1-knockdown experiments demonstrated that HMGB1 is required for efficient viral gene expression. However, despite its proviral role in viral replication, we found that HMGB1 levels decreased in late stages of infection due to transcriptional downregulation. Furthermore, by overexpressing HMGB1, we showed that this regulation of HMGB1 levels during infection is critical for optimal HAdV-C5 replication. These results highlight the complex regulatory relationship between HMGB1 and HAdV-C5 infection. IMPORTANCE: In an extensive proteomics analysis, we found that HMGB1, an important cellular chromatin protein, was enriched in adenovirus replication compartments. In this study, we aimed to better understand the role of HMGB1 in the infection process of a human DNA virus, HAdV-C5. We tested different virus types, including some with specific gene deletions and mutations. Our results showed that during infection, HMGB1 levels decreased because the virus suppressed its production. Despite this, even at lower levels, HMGB1 still helped the virus replicate by interacting with key viral proteins and DNA at sites where the virus is actively replicating. Overall, our findings highlight how HMGB1 plays a crucial role in facilitating efficient virus replication, making it an important factor in the infection process.

HMGB1 Protein↗

PubMed2025

Pooled PPIseq: Screening the SARS-CoV-2 and human interface with a scalable multiplexed protein-protein interaction assay platform.

Protein-Protein Interactions (PPIs) are a key interface between virus and host, and these interactions are important to both viral reprogramming of the host and to host restriction of viral infection. In particular, viral-host PPI networks can be used to further our understanding of the molecular mechanisms of tissue specificity, host range, and virulence. At higher scales, viral-host PPI screening could also be used to screen for small-molecule antivirals that interfere with essential viral-host interactions, or to explore how the PPI networks between interacting viral and host genomes co-evolve. Current high-throughput PPI assays have screened entire viral-host PPI networks. However, these studies are time consuming, often require specialized equipment, and are difficult to further scale. Here, we develop methods that make larger-scale viral-host PPI screening more accessible. This approach combines the mDHFR split-tag reporter with the iSeq2 interaction-barcoding system to permit massively-multiplexed PPI quantification by simple pooled engineering of barcoded constructs, integration of these constructs into budding yeast, and fitness measurements by pooled cell competitions and barcode-sequencing. We applied this method to screen for PPIs between SARS-CoV-2 proteins and human proteins, screening in triplicate >180,000 ORF-ORF combinations represented by >1,000,000 barcoded lineages. Our results complement previous screens by identifying 74 putative PPIs, including interactions between ORF7A with the taste receptors TAS2R41 and TAS2R7, and between NSP4 with the transmembrane KDELR2 and KDELR3. We show that this PPI screening method is highly scalable, enabling larger studies aimed at generating a broad understanding of how viral effector proteins converge on cellular targets to effect replication.

Humans↗

PubMed2026

A python based automated computational framework to classify and comparative genomics analysis of the global diversity of chili leaf curl virus (ChiLCV) strains to understand virus host interactions.

Chili leaf curl virus (ChiLCV) is a Begomovirus chillicapsici that is one of the most devastating viruses impacted on the production of chili in the world, especially in South Asia. In the present study, we combined high-throughput computational genomics with experimental analysis of global diversity. A workflow was created using automated Python scripts to download, curate and process ChiLCV genomes from public database. About 410 complete ChiLCV genomes download from public databases. Using a phylogenetic approach, these isolates were subdivided into 34 strains, belonging to 10 major clades, showing significant genetic diversity. Geographic analysis revealed that Pakistan (207 isolates) and India (148 isolates) were the main sources of ChiLCV diversity and the remainder of the isolates were from Oman, Bangladesh, Iran, Saudi Arabia and Sri Lanka. Recombination was observed as a major evolutionary force as more than twenty recombination events were detected. Analysis of cis-regulatory elements showed a complex structure of the viral promoter, including multiple binding sites for transcription factors, hormone-response elements, light-responsive elements, and stress-responsive elements, indicating a high number of interactions between viral regulatory elements and host signaling pathways. Pangenome analysis showed the presence of a highly dynamic open pangenome made up of strain-specific orthologous groups (species-specific orthogroups). Experimental inoculation of chili plants was also carried out to assess the biological effects of infection, along with phytochemical, FTIR, HPLC, and qPCR analyses.

Begomovirus↗

PubMed2026

Population heterogeneity in Helicobacter pylori PMSS1 shapes variable mouse infectivity: derivation of the homogeneous reference strain PMSS2.

UNLABELLED: Experimental infection models are widely used to investigate host-microbe interactions, often under the assumption that bacterial populations are genetically uniform. Here, we examined population heterogeneity in the widely used Helicobacter pylori strain PMSS1 and its relationship to variation in mouse infectivity. Single-colony isolates derived from PMSS1 displayed substantial differences in colonization efficiency, indicating that pre-existing variation within the population contributes to infection outcomes. To distinguish the effects of initial population heterogeneity from changes arising during infection, we analyzed PMSS2, a genetically homogeneous reference strain derived from PMSS1 that exhibited consistent infection phenotypes across independently isolated clones. Comparative genomic analysis of isolates recovered from infected mice revealed differences in the extent and patterns of genomic variation between PMSS1- and PMSS2-derived populations. These results demonstrate that variability in infection outcomes can arise from pre-existing heterogeneity within bacterial populations and highlight the importance of considering population composition when interpreting experimental infection studies. IMPORTANCE: Animal infection models are widely used to study how bacterial pathogens cause disease and change during infection. These studies often assume that the bacteria used for infection are genetically uniform. Our study shows that this assumption may not always hold. We found that a commonly used Helicobacter pylori strain contains hidden genetic diversity that leads to large differences in how well bacteria infect mice. By comparing this strain with a genetically uniform derivative, we show how differences present before infection can shape infection outcomes and influence the genetic changes observed during infection. Our findings highlight the importance of considering starting population diversity when interpreting experimental infection studies and are broadly relevant to research on microbial pathogenesis.

Helicobacter pylori↗

PubMed2025

Proximity interactome of alphavirus replicase component nsP3 includes proviral host factors eIF4G and AHNAK.

All positive-strand RNA viruses replicate their genomes in association with modified intracellular membranes, inducing either membrane invaginations termed spherules, or double-membrane vesicles. Alphaviruses encode four non-structural proteins nsP1-nsP4, all of which are essential for RNA replication and spherule formation. To understand the host factors associated with the replication complex, we fused the efficient biotin ligase miniTurbo with Semliki Forest virus (SFV) nsP3, which is located on the cytoplasmic surface of the spherules. We characterized the proximal proteome of nsP3 in three cell lines, including cells unable to form stress granules, and identified >300 host proteins constituting the microenvironment of nsP3. These included all the nsPs, as well as several previously characterized nsP3 binding proteins. However, the majority of the identified interactors had no previously identified roles in alphavirus replication, including 39 of the top 50 interacting proteins. The most prominent biological processes involving the proximal proteins were nucleic acid metabolism, translational regulation, cytoskeletal rearrangement and membrane remodeling. siRNA silencing confirmed six novel proviral factors, USP10, AHNAK, eIF4G1, SH3GL1, XAB2 and ANKRD17, which are associated with distinct cellular functions. All of these except SH3GL1 were also important for the replication of chikungunya virus. We discovered that the small molecule 4E1RCat, which inhibits the interaction between the canonical translation initiation factors eIF4G and eIF4E, exhibits antiviral activity against SFV. Since the same molecule was previously found to inhibit coronaviruses, this suggest the possibility that translation initiation factors could be considered as targets for broadly acting antivirals.

Viral Nonstructural Proteins↗

PubMed2026

A Novel Approach to Engineering Tomato Spotted Wilt Virus Infectious Clones by Disarming Key Nodes in Antiviral Defenses.

Tomato spotted wilt virus (TSWV) is an economically devastating pathogen that rapidly overcomes genetic resistance in major crops. Reverse genetic systems are crucial for investigating plant-virus interactions and resistance-breaking mechanisms, and developing these tools for segmented ambisense RNA viruses remains a crucial challenge. Current TSWV clones rely on extensively modified Asian isolates requiring co-delivery of multiple replication helpers and viral silencing suppressors. Streamlining these systems for regionally significant strains with minimal genetic alterations is essential. Here, we developed the first infectious clone of a U.S. TSWV isolate (PA01). Three binary plasmids contain cDNAs for the antigenomic L and S segments, as well as the genomic M segment, with enhanced GFP replacing NSs on the S segment. Co-delivery of the cucumovirus 2b alone or in combination with tombusvirus P19 or begomovirus AL2 achieved a high proportion of systemically infected Nicotiana benthamiana and Capsicum annuum plants. In N. tabacum, co-delivering the Caenorhabditis elegans cell death suppressor CED-9 or using NahG transgenic plants produced 30 to 33% systemically infected plants. Co-delivery of 2b boosted infection levels in NahG plants to 62%. These data indicate that in addition to the antiviral RNA-silencing machinery, additional host defense pathways influence TSWV rescue and systemic infection from cDNA. [Formula: see text] Copyright © 2026 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Tospovirus↗

PubMed2025

Barley resistance and susceptibility to fungal cell entry involve the interplay of ROP signaling with phosphatidylinositol-monophosphates.

Rho-of-plant small GTPases (ROPs) are regulators of plant polar growth and of plant-pathogen interactions. The barley ROP, RACB, is involved in susceptibility toward infection by the barley powdery mildew fungus Blumeria hordei (Bh) but little is known about the cellular pathways that connect RACB signaling to disease susceptibility. Here we identify novel RACB interaction partners of plant or fungal origin by untargeted co-immunoprecipitation of constitutively active (CA) RACB tagged by green fluorescent protein from Bh-infected barley epidermal layers and subsequent analysis by liquid chromatography-coupled mass spectrometry. Three of the immunoprecipitated proteins, a plant phosphoinositide phosphatase, a plant phosphoinositide phospholipase, and a putative Bh-effector protein, are involved in the barley-Bh-pathosystem and support disease resistance or susceptibility, respectively. RACB and its plant interactors bind to overlapping anionic phospholipid species in vitro, and in the case of RACB, this lipid interaction is mediated by its carboxy-terminal polybasic region (PBR). Fluorescent markers for anionic phospholipids show altered subcellular distribution in barley cells during Bh attack and under expression of a RACB-binding fungal effector. Phosphatidylinositol 4-phosphate, phosphatidylinositol 3,5-bisphosphate, and phosphatidylserine show a distinct enrichment at the haustorial neck region, suggesting a connection to subcellular targeting of RACB at this site. The interplay of ROPs with anionic phospholipids and phospholipid-metabolizing enzymes may thus enable the subcellular enrichment of components pivotal for success or failure of fungal penetration.

Hordeum↗

PubMed2026

The msf gene causes condition-specific shifts in global gene expression in Haemophilus influenzae.

UNLABELLED: Haemophilus influenzae is a diverse human-restricted bacterium that normally colonizes the healthy nasopharynx but also causes common infections. Comparisons of clinical isolate genomes previously identified a gene, msf, that contained Sel1-like repeats that were associated with clinical disease. Mutant analysis had further found that msf improved survival in macrophages and increased systemic infection in an animal model. However, the role of msf in other conditions and its molecular function remain unknown. To identify protein-protein interactions with Msf, a yeast two-hybrid screen against an H. influenzae prey library was conducted, which found potential interactions with lipoprotein exporter protein LolD and an autotransporter adhesin Hap. To identify effects of msf on gene expression, we compared wild-type and mutant strains grown in multiple culture conditions by RNA-seq. The results indicate that msf modulates global gene expression in a condition-dependent manner, exerting an especially strong influence in starved surface-attached biofilm cells. The few consistent changes in mutants' planktonic exponential and stationary phases included decreased expression of two paralogous autotransporter adhesins. By contrast, mutant cells in starved surface-attached biofilms had dramatic changes in expression, including upregulation of protein translation and downregulation of alternative carbon metabolism. However, assays of 24 hour biofilm phenotypes found only subtle gene expression changes. Together, the results point to a speculative model of Msf functioning as an envelope-associated chaperone whose presence affects the relative expression of proteins at the outer membrane. IMPORTANCE: Comparing genomes from different clinical isolates of the same pathogenic bacterial species has identified genes associated with virulence, but many of these are understudied or have no known function. The msf gene was previously implicated as a virulence factor in Haemophilus influenzae, a common cause of mucosal diseases including middle-ear and chronic lung infections. This study finds that the msf gene causes condition-specific changes in gene expression, with especially dramatic changes in starved surface-attached biofilm cells. Along with identification of putative protein-protein interaction partners, the results provide new clues as to the molecular and cellular function of Msf, potentially as an envelope-associated chaperone involved in membrane protein trafficking. Understanding how virulence-associated genes like msf modulate bacterial responses to the environment may help explain why some bacterial strains remain harmless colonizers while others become pathogens.

Haemophilus influenzae↗

PubMed2025

Evolutionary and Functional Analysis of Caspase-8 and ASC Interactions to Drive Lytic Cell Death, PANoptosis.

Caspases are evolutionarily conserved proteins essential for driving cell death in development and host defense. Caspase-8, a key member of the caspase family, is implicated in nonlytic apoptosis, as well as lytic forms of cell death. Recently, caspase-8 has been identified as an integral component of PANoptosomes, multiprotein complexes formed in response to innate immune sensor activation. Several innate immune sensors can nucleate caspase-8-containing PANoptosome complexes to drive inflammatory lytic cell death, PANoptosis. However, how the evolutionarily conserved and diverse functions of caspase-8 drive PANoptosis remains unclear. To address this, we performed evolutionary, sequence, structural, and functional analyses to decode caspase-8's complex-forming abilities and its interaction with the PANoptosome adaptor ASC. Our study distinguished distinct subgroups within the death domain superfamily based on their evolutionary and functional relationships, identified homotypic traits among subfamily members, and captured key events in caspase evolution. We also identified critical residues defining the heterotypic interaction between caspase-8's death effector domain and ASC's pyrin domain, validated through cross-species analyses, dynamic simulations, and in vitro experiments. Overall, our study elucidated recent evolutionary adaptations of caspase-8 that allowed it to interact with ASC, improving our understanding of critical molecular associations in PANoptosome complex formation and the underlying PANoptotic responses in host defense and inflammation. These findings have implications for understanding mammalian immune responses and developing new therapeutic strategies for inflammatory diseases.

Caspase 8↗

PubMed2025

Global siRNA screen identifies human host factors critical for SARS-CoV-2 replication and late stages of infection.

Defining the subset of cellular factors governing SARS-CoV-2 replication can provide critical insights into viral pathogenesis and identify targets for host-directed antiviral therapies. While a number of genetic screens have previously reported SARS-CoV-2 host dependency factors, most of these approaches relied on utilizing pooled genome-scale CRISPR libraries, which are biased toward the discovery of host proteins impacting early stages of viral replication. To identify host factors involved throughout the SARS-CoV-2 infectious cycle, we conducted an arrayed genome-scale siRNA screen. Resulting data were integrated with published functional screens and proteomics data to reveal (i) common pathways that were identified in all OMICs datasets-including regulation of Wnt signaling and gap junctions, (ii) pathways uniquely identified in this screen-including NADH oxidation, or (iii) pathways supported by this screen and proteomics data but not published functional screens-including arachionate production and MAPK signaling. The identified proviral host factors were mapped into the SARS-CoV-2 infectious cycle, including 32 proteins that were determined to impact viral replication and 27 impacting late stages of infection, respectively. Additionally, a subset of proteins was tested across other coronaviruses revealing a subset of proviral factors that were conserved across pandemic SARS-CoV-2, epidemic SARS-CoV-1 and MERS-CoV, and the seasonal coronavirus OC43-CoV. Further studies illuminated a role for the heparan sulfate proteoglycan perlecan in SARS-CoV-2 viral entry and found that inhibition of the non-canonical NF-kB pathway through targeting of BIRC2 restricts SARS-CoV-2 replication both in vitro and in vivo. These studies provide critical insight into the landscape of virus-host interactions driving SARS-CoV-2 replication as well as valuable targets for host-directed antivirals.

Humans↗

PubMed2005

[Relationship among HPV16 infection and Expression of hTERT, p21waf1, Ki67 in cervical intraepithelial neoplasias and squamous cell carcinomas of cervix uteri].

BACKGROUND: To investigate the relationship among human papillomavirus (HPV)16 infection and the expression of telomerase catalytic protein subunit (hTERT), tumor suppressor gene p21waf1, proliferation antigen Ki67 in cervical intraepithelial neoplasias (CIN) and squamous cell carcinomas (SCC) of cervix uteri and their significance. METHODS: Tissue microarray combined with in situ hybridization (ISH) and immunohistochemical staining (EliVision plus method) was used to detect the expression of HPV16 RNA, hTERT, Ki67 and p21waf1 proteins in the cervix uteri specimens from 130 subjects, including normal cervical tissue (n=26), CIN (n=46) and SCC (n=58). RESULTS: (1) The positive rate of HPV16 hybridization signals and expression of hTERT, Ki67 in CINII-III, in situ carcinoma and invasive SCC were all significantly higher than in normal cervical tissue (P < 0.05 for all), and was also higher in SCC than in CIN (P < 0.05 for all). There was a significant difference among CIN I, II and III (P < 0.05 for all). (2) The positive expression of p21waf1 protein only in SCC was significantly lower than in normal cervical tissue (P < 0.05), but there was no significant differences among other groups (all P > 0.05). (3) The positive rate of HPV16 and the expression of Ki67 showed respectively positive being correlated with the expression of hTERT (P < 0.05, r=0.339; P < 0.05, r=0.398); HPV16, hTERT and Ki67 showed respectively negative correlation with the expression of p21waf1 (P < 0.05, r=-0.337; P < 0.05, r=-0.248; P < 0.05, r=-0.446); There was no significant relation between HPV16 and Ki67 (P > 0.05). CONCLUSION: The results suggest that in tissues of CIN and SCC changes in hTERT, p21waf1 and Ki67 expression may be associated with HPV16 infection and they interact with each other, which can influent the progression of CIN and carcinogenesis of SCC. These biomarkers may be analyzed comprehensively to reveal the detailed mechanism by which HPV16 participate in malignant transformation and to provide some informations on the diagnosis of patients with high risk for malignant progression. Tissue microarray is an efficient platform for high-throughput analysis of genes and their expression products in investigations.

Carcinoma, Squamous Cell↗

PubMed2004

Probing Trypanosoma cruzi biology with DNA microarrays.

The application of genome-scale approaches to study Trypanosoma cruzi-host interactions at different stages of the infective process is becoming possible with sequencing and assembly of the T. cruzi genome nearing completion and sequence information available for both human and mouse genomes. Investigators have recently begun to exploit DNA microarray technology to analyze host transcriptional responses to T. cruzi infection and dissect developmental processes in the complex T. cruzi life-cycle. Collectively, information generated from these and future studies will provide valuable insights into the molecular requirements for establishment of T. cruzi infection in the host and highlight the molecular events coinciding with disease progression. While the field is in its infancy, the availability of genomic information and increased accessibility to relatively high-throughput technologies represents a significant advancement toward identification of novel drug targets and vaccine candidates for the treatment and prevention of Chagas' disease.

Animals↗