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Herpesviruses utilize various host factors to establish latent infection, survival, and spread disease in the host. These factors include host cellular machinery, host proteins, gene expression, multiple transcription factors, cellular signal pathways, immune cell activation, transcription factors, cytokines, angiogenesis, invasion, and factors promoting metastasis. The knowledge and understanding of host genes, protein products, and biochemical pathways lead to discovering safe and effective antivirals to prevent viral reactivation and spread infection. Here, we focus on the contribution of pro-inflammatory, anti-inflammatory, and resolution lipid metabolites of the arachidonic acid (AA) pathway in the lifecycle of herpesvirus infections. We discuss how various herpesviruses utilize these lipid pathways to their advantage and how we target them to combat herpesvirus infection. We also summarize recent development in anti-herpesvirus therapeutics and new strategies proposed or under clinical trials. These anti-herpesvirus therapeutics include inhibitors blocking viral life cycle events, engineered anticancer agents, epigenome influencing factors, immunomodulators, and therapeutic compounds from natural extracts.

Shiga toxin is the major virulence factor of enterohemorrhagic Escherichia coli (EHEC), and the gene encoding it is carried within the genome of Shiga toxin-converting phages (Stx phages). Numerous Stx phages have been sequenced to gain a better understanding of their contribution to the virulence potential of EHEC. The Stx phages are classified into the lambdoid phage family based on similarities in lifestyle, gene arrangement, and nucleotide sequence to the lambda phages. This study explores the replication regions of non-lambdoid Stx phages that completely lack the O and P genes encoding the proteins involved in initiating replication in the lambdoid phage genome. Instead, they carry sequences encoding replication proteins that have not been described earlier, here referred to as eru genes (after EHEC phage replication unit genes). This study identified three different types of Eru-phages, where the Eru1-type is carried by the highly pathogenic EHEC strains that caused the Norwegian O103:H25 outbreak in 2006 and the O104:H4 strain that caused the large outbreak in Europe in 2011. We show that Eru1-phages exhibit a less stable lysogenic state than the classical lambdoid Stx phages. As production of phage particles is accompanied by production of Stx toxin, the Eru1-phage could be associated with a high-virulence phenotype of the host EHEC strain. This finding emphasizes the importance of classifying Stx phages according to their replication regions in addition to their Stx-type and could be used to develop a novel strategy to identify highly virulent EHEC strains for improved risk assessment and management.

Herpesviruses utilize various host factors to establish latent infection, survival, and spread disease in the host. These factors include host cellular machinery, host proteins, gene expression, multiple transcription factors, cellular signal pathways, immune cell activation, transcription factors, cytokines, angiogenesis, invasion, and factors promoting metastasis. The knowledge and understanding of host genes, protein products, and biochemical pathways lead to discovering safe and effective antivirals to prevent viral reactivation and spread infection. Here, we focus on the contribution of pro-inflammatory, anti-inflammatory, and resolution lipid metabolites of the arachidonic acid (AA) pathway in the lifecycle of herpesvirus infections. We discuss how various herpesviruses utilize these lipid pathways to their advantage and how we target them to combat herpesvirus infection. We also summarize recent development in anti-herpesvirus therapeutics and new strategies proposed or under clinical trials. These anti-herpesvirus therapeutics include inhibitors blocking viral life cycle events, engineered anticancer agents, epigenome influencing factors, immunomodulators, and therapeutic compounds from natural extracts. [ABSTRACT FROM AUTHOR]

Shiga toxin is the major virulence factor of enterohemorrhagic Escherichia coli (EHEC), and the gene encoding it is carried within the genome of Shiga toxin-converting phages (Stx phages). Numerous Stx phages have been sequenced to gain a better understanding of their contribution to the virulence potential of EHEC. The Stx phages are classified into the lambdoid phage family based on similarities in lifestyle, gene arrangement, and nucleotide sequence to the lambda phages. This study explores the replication regions of non-lambdoid Stx phages that completely lack the O and P genes encoding the proteins involved in initiating replication in the lambdoid phage genome. Instead, they carry sequences encoding replication proteins that have not been described earlier, here referred to as eru genes (after E HEC phage r eplication u nit genes). This study identified three different types of Eru-phages, where the Eru1-type is carried by the highly pathogenic EHEC strains that caused the Norwegian O103:H25 outbreak in 2006 and the O104:H4 strain that caused the large outbreak in Europe in 2011. We show that Eru1-phages exhibit a less stable lysogenic state than the classical lambdoid Stx phages. As production of phage particles is accompanied by production of Stx toxin, the Eru1-phage could be associated with a high-virulence phenotype of the host EHEC strain. This finding emphasizes the importance of classifying Stx phages according to their replication regions in addition to their Stx-type and could be used to develop a novel strategy to identify highly virulent EHEC strains for improved risk assessment and management. [ABSTRACT FROM AUTHOR]

Salmonella biofilm prevention and control is of great importance. This study, investigated the use of the isolated phage KM16 belonging to the family Myoviridae in the order Caudovirales. The phage genome size was 170,126 bp. Almost all phages were adsorbed to the host within 20 min. KM16 had a latent period of 70 min followed by a rise period of 40 min. Phage KM16 had the ability to lytically infect 10 out of the 12 clinical strains of S. paratyphi tested. Phylogenetic analysis indicated that the S. paratyphi 16S rRNA, crispr 1 and fimA genes correlated with the lytic spectrum of phage KM16. The lytic spectrum of phage KM16 correlated with Salmonella pili (fimA), and Salmonella pili were the recognition site for phage adsorption to the host. Phage KM16 (MOI = 0.1) had a better anti-biofilm effect than kanamycin sulfate (10 ug ml−1) in high-concentration Salmonella cultures. [ABSTRACT FROM AUTHOR]

1. The objective of this study was to investigate the potential immunomodulatory effects of yeast (Saccharomyces cerevisiae) and yeast-derived products treated with a cell wall lytic enzyme mixture on the gene expression of toll-like receptors and cytokines of chicken B cell line (DT 40) stimulated with lipopolysaccharide. 2. The effect of brewer's yeast (Y), yeast cell wall (YCW), distilled dried grains with solubles (DDGS) and a processed yeast + nucleotide-rich product (PY/N) treated with a yeast cell wall lytic enzyme (E) was assessed using a chicken B cells and LPS challenge model. 3. Relative gene expression of toll-like receptors (TLRs) and cytokines was investigated. Treatment of cells with Y, YCW, YCW + E and PY/N upregulated the expression of TLR2b following LPS challenge. Gene expression of TLR4 was downregulated in E, YCW and YCW + E treatments compared to control, while adding DDGS and PY/N upregulated the expression of TLR4 either before or after enzyme treatment. Following LPS challenge, expression of IL-4 and IL-10 was upregulated in cells treated with YCW and PY/N, both pre and post enzyme incubation. Adding YCW and PY/N to the cells challenged with LPS upregulated the expression of IFN-γ and IL-12 before and after enzyme treatment. Treatment of cells with YCW, DDGS and PY/N increased the expression of IL-6 prior to LPS challenge. 4. In conclusion, the results suggested that yeast-derived products affected immunomodulatory activities by changing the expression of cytokines involved in the innate immune response. [ABSTRACT FROM AUTHOR]

Lytic lesions in adult spine are a common manifestation of aggressive disease such as primary bone tumor, metastasis, myeloma, or infectious pathology. Xanthoma arising in the spine with purely intraosseous component is an extremely rare occurrence with only six cases reported in the adult population, none in the cervical region. We report the first case of primary xanthoma of the cervical spine in a 50-year-old male solely confined to osseous compartment. The imaging mimics of lytic lesion with expansile mass in adult spine are reiterated. [ABSTRACT FROM AUTHOR]

Background neonatal sepsis is considered as one of the main causes of morbidity and mortality in preterm and full-term neonates. It is a clinical disorder caused by bacterial infections of blood stream. Enterobacteriaceae group (including Klebsiella Pneumonia and Escherichia coli) is a gramnegative (G-ve) bacteria which is one of the most serious causative organisms of neonatal sepsis. Klebsiella Pneumonia and Escherichia coli phages are bacterial viruses that infect bacteria and pursue in two possible ways: lytic and lysogenic life cycle. The risk of neonatal sepsis increase with multi drug resistant organisms which make the treatment of their infections difficult. Therefore, antibiotics and phage combinations are possible choices to solve this problem. Aims of the study: this study aims to evaluate the antibacterial activity of bacteriophages alone and in combination with certain antibiotics against most common Enterobacteriaceae that cause neonatal sepsis and to obtain desired antibacterial combinations for the treatment of most common Enterobacteriaceae in neonatal sepsis with synergistic effects. Materials and Methods: thirty isolated bacterial cultures from blood samples of neonates with sepsis were collected from the laboratories of Al- Kadimia pediatric hospital and Central teaching hospital of pediatric from December 2019 to March 2020. They were identified using morphological characteristics, Api20E test and by Vitek2 compact system. Fourteen isolates among them (46.67%) were Klebsiella Pneumonia and eleven isolates (36.67%) were Esherichia Coli. Results: The bacterial profile of the collected isolates was found as follows: Klebsiella Pneumonia (46.67%), E.Coli(36.67%), Enterobacter(13.33%) and Serratia (3.33%). The percentages of resistance to the tested antibiotics were as follows: of Klebsiella Pneumonia isolates amikacin14.28%, aztreonam, cefepime and ceftazidime 71.43% for each, ciprofloxacin 7.14%, piperacillin/tazobactam, gentamicin, tobramycin, imipenem and meropenem 21.43% for each, minocycline 0%, piperacillin 78.57%, ticarcillin 100%, ticarcillin/clavulanic acid 50%, and trimethoprimsulfamethoxazole 28.57%. For Escherichia Coli isolates amikacin 0%, aztreonam, ticarcillin, piperacillin, cefepime and ceftazidime 72.73% for each, piperacillin/tazobactam, ticarcillin/clavulanic acid, ciprofloxacin and trimethoprim-sulfamethoxazole 27.27% for each, gentamicin, tobramycin and minocycline 9.09% for each, imipenem and meropenem 18.18%. (64.29%) of Klebsiella Pneumonia isolates and (45.45%) of E.Coli were MDR. Antibiotic-antibiotic combinations of piperacillin/tazobactam or ceftazidime with amikacin for isolate 11, piperacillin/tazobactam or amikacin with ceftazidime for isolate 12 were resulted in synergistic effects. Also, antibioticantibiotic combinations of piperacillin/tazobactam or ceftazidime with amikacin for isolates 4 and 6 resulted in synergistic effects. Combinations of phage with each of 1/4and 1/2 MIC piperacillin/tazobactam or ceftazidime for tested isolates (4and6 which were E.Coli and Klebsiella Pneumoia respectively) and phage with 1/4 and 1/2 MIC amikacin for E.Coli isolate 4 showed synergistic effects to the antibiotics. Conclusions: all combinations of piperacillin/tazobactam, ceftazidime with amikacin and phage-antibiotic combinations with piperacillin/tazobactam, ceftazidime or amikacin showed highly synergistic effects against resistant and MDR Klebsiella Pneumonia and E.Coli strains that cause neonatal sepsis. [ABSTRACT FROM AUTHOR]

Foodborne Shiga toxin-producing Escherichia coli (STEC) cause severe diarrhea and hemolytic uremic syndrome (HUS) in humans. However, traditional methods for STEC sterilization are difficult to apply to fresh food. To control the pathogen, phage infecting E. coli O157:H7 were isolated and characterized. The isolated phage vB_EcoM-ECP26 had an icosahedral head and a contractile tail, and was classified as belonging to the Myoviridae family. The phage showed a broad host range against STEC and exhibited a large burst size of 1914 PFU/cell. The phage was highly stable at high temperatures (65 °C) and wide ranges of pH (4–10). The genome of vB_EcoM-ECP26 consists of 136,993 nucleotides, 214 open reading frames, and does not contain lysogenicity-related genes. Phylogenetic analysis showed that vB_EcoM-ECP26 is a V5-like species. STEC O157 growth was inhibited by vB_EcoM-ECP26 for 8 h. Furthermore, this phage not only significantly decreased the STEC population (p < 0.05), but also persisted in fresh lettuce at 4 °C for 5 days. Therefore, these results reveal that the novel lytic phage vB_EcoM-ECP26 could be a useful agent for the control of foodborne STEC. [ABSTRACT FROM AUTHOR]

Microbiomes feature complex interactions between diverse bacteria and bacteriophages. Synthetic microbiomes offer a powerful way to study these interactions; however, a major challenge is obtaining a representative bacteriophage population during the bacterial isolation process. We demonstrate that colony isolation reliably excludes virulent viruses from sample sources with low virion-to-bacteria ratios such as feces, creating "virulent virus-free" controls. When the virulent dsDNA virome is reintroduced to a 73-strain synthetic gut microbiome in a bioreactor model of the human colon, virulent viruses target susceptible strains without significantly altering community structure or metabolism. In addition, we detected signals of prophage induction that associate with virulent predation. Overall, our findings indicate that dilution-based isolation methods generate synthetic gut microbiomes that are heavily depleted, if not devoid, of virulent viruses and that such viruses, if reintroduced, have a targeted effect on community assembly, metabolism, and prophage replication. [Display omitted] • A mathematical model accurately predicts frequencies of infected colonies • Colonies isolated from feces are heavily depleted in virulent viruses • Reintroducing virulent viruses impacts susceptible microbes and their prophages • Virulent viruses minimally impact structure and metabolism of a 73-strain community Wilde et al. show that colony isolation reliably removes virulent viruses from gut bacteria, creating "virus-free" communities. By reintroducing the virulent virome to a complex bacterial community, Wilde et al. show that virulent viruses have a highly specific impact on community members and their prophages. [ABSTRACT FROM AUTHOR]

Various species of Alexandrium can produce a number of bioactive compounds, e.g., paralytic shellfish toxins (PSTs), spirolides, gymnodimines, goniodomins, and also uncharacterised bioactive extracellular compounds (BECs). The latter metabolites are released into the environment and affect a large range of organisms (from protists to fishes and mammalian cell lines). These compounds mediate allelochemical interactions, have anti-grazing and anti-parasitic activities, and have a potentially strong structuring role for the dynamic of Alexandrium blooms. In many studies evaluating the effects of Alexandrium on marine organisms, only the classical toxins were reported and the involvement of BECs was not considered. A lack of information on the presence/absence of BECs in experimental strains is likely the cause of contrasting results in the literature that render impossible a distinction between PSTs and BECs effects. We review the knowledge on Alexandrium BEC, (i.e., producing species, target cells, physiological effects, detection methods and molecular candidates). Overall, we highlight the need to identify the nature of Alexandrium BECs and urge further research on the chemical interactions according to their ecological importance in the planktonic chemical warfare and due to their potential collateral damage to a wide range of organisms.

The interaction between gut bacterial and viral microbiota is thought to be important in human health. While fluctuations in female genital tract (FGT) bacterial microbiota similarly determine sexual health, little is known about the presence, persistence, and function of vaginal bacteriophages. We conducted shotgun metagenome sequencing of cervicovaginal samples from South African adolescents collected longitudinally, who received no antibiotics. We annotated viral reads and circular bacteriophages, identified CRISPR loci and putative prophages, and assessed their diversity, persistence, and associations with bacterial microbiota composition. Siphoviridae was the most prevalent bacteriophage family, followed by Myoviridae, Podoviridae, Herelleviridae, and Inoviridae. Full-length siphoviruses targeting bacterial vaginosis (BV)-associated bacteria were identified, suggesting their presence in vivo. CRISPR loci and prophage-like elements were common, and genomic analysis suggested higher diversity among Gardnerella than Lactobacillus prophages. We found that some prophages were highly persistent within participants, and identical prophages were present in cervicovaginal secretions of multiple participants, suggesting that prophages, and thus bacterial strains, are shared between adolescents. The number of CRISPR loci and prophages were associated with vaginal microbiota stability and absence of BV. Our analysis suggests that (pro)phages are common in the FGT and vaginal bacteria and (pro)phages may interact.

Introduction . Acinetobacter baumannii is a critical priority pathogen for novel antimicrobials (World Health Organization) because of the rise in nosocomial infections and its ability to evolve resistance to last resort antibiotics. A. baumannii is thus a priority target for phage therapeutics. Two strains of a novel, virulent bacteriophage (LemonAid and Tonic) able to infect carbapenem-resistant A. baumannii (strain NCTC 13420), were isolated from environmental water samples collected through a citizen science programme. Gap statement. Phage-host coevolution can lead to emergence of host resistance, with a concomitant reduction in the virulence of host bacteria; a potential benefit to phage therapy applications. Methodology. In vitro and in vivo assays, genomics and microscopy techniques were used to characterize the phages; determine mechanisms and impact of phage resistance on host virulence, and the efficacy of the phages against A. baumannii . Results. A. baumannii developed resistance to both viruses, LemonAid and Tonic. Resistance came at a cost to virulence, with the resistant variants causing significantly reduced mortality in a Galleria mellonella larval in vivo model. A replicated 8 bp insertion increased in frequency (~40 % higher frequency than in the wild-type) within phage-resistant A. baumannii mutants, putatively resulting in early truncation of a protein of unknown function. Evidence from comparative genomics and an adsorption assay suggests this protein acts as a novel phage receptor site in A. baumannii . We find no evidence linking resistance to changes in capsule structure, a known virulence factor. LemonAid efficiently suppressed growth of A. baumanni in vitro across a wide range of titres. However, in vivo , while survival of A. baumannii infected larvae significantly increased with both remedial and prophylactic treatment with LemonAid (10 7 p.f.u. ml -1 ), the effect was weak and not sufficient to save larvae from morbidity and mortality. Conclusion. While LemonAid and Tonic did not prove effective as a treatment in a Galleria larvae model, there is potential to harness their ability to attenuate virulence in drug-resistant A. baumannii .

The diagnosis of a large solitary lytic skull vault lesion in adults is a challenge due to variable aggressiveness and overlapping features. The purpose of this article is to demonstrate the use of an imaging approach to narrow the differential diagnosis when a large solitary lytic skull vault lesion is encountered. The initial imaging assessment using computed tomography (CT) is invaluable in determining lesion aggressiveness based on bony margins and skull tables involvement. Further assessment with magnetic resonance (MR) imaging including diffusion weighted imaging (DWI) aids in soft tissue characterization. We present cases of large solitary lytic skull vault lesions in adults, emphasizing on salient and atypical imaging features, with pathological correlation for better understanding of the disease processes that underlie the imaging features. • Evaluation of solitary lytic skull vault lesion using a CT diagnostic algorithm is discussed. • The utility of MRI with DWI aids in characterization of the soft tissue component. • Imaging correlation with pathological features improves understanding of the disease processes. [ABSTRACT FROM AUTHOR]

Mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cellular metabolism. In nutrient-rich environments, mTORC1 kinase activity stimulates protein synthesis to meet cellular anabolic demands. Under nutrient-poor conditions or under stress, mTORC1 is rapidly inhibited, global protein synthesis is arrested, and a cellular catabolic process known as autophagy is activated. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes multiple proteins that stimulate mTORC1 activity or subvert autophagy, but precise roles for mTORC1 in different stages of KSHV infection remain incompletely understood. Here, we report that during latent and lytic stages of KSHV infection, chemical inhibition of mTORC1 caused eukaryotic initiation factor 4F (eIF4F) disassembly and diminished global protein synthesis, which indicated that mTORC1-mediated control of translation initiation was largely intact. We observed that mTORC1 was required for synthesis of the replication and transcription activator (RTA) lytic switch protein and reactivation from latency, but once early lytic gene expression had begun, mTORC1 was not required for genome replication, late gene expression, or the release of infectious progeny. Moreover, mTORC1 control of autophagy was dysregulated during lytic replication, whereby chemical inhibition of mTORC1 prevented ULK1 phosphorylation but did not affect autophagosome formation or rates of autophagic flux. Together, these findings suggest that mTORC1 is dispensable for viral protein synthesis and viral control of autophagy during lytic infection and that KSHV undermines mTORC1- dependent cellular processes during the lytic cycle to ensure efficient viral replication. [ABSTRACT FROM AUTHOR]

The diagnosis of bloodstream infection requires the optimum combination of media in an automated blood culture system for maximum recovery of pathogens with the earliest time to detection. In a previous work, we showed that for patients admitted to the Emergency Department of our hospital, the combination of BACTEC lytic anaerobic and BACTEC aerobic vials was more efficient than BACTEC anaerobic and BACTEC aerobic vial. In this study, we extended the work including a broader patient population, representative of all hospital. A total of 8629 cultures were collected during the pre-lytic phase, from 01 July 2013 to 30 June 2014 and 7940 cultures during the post-lytic phase, ranged from 01 July 2015 to 30 June 2016. The number of positive blood cultures was higher during the post-lytic phase (19.74%) than in the pre-lytic phase (17.52%), particularly for Escherichia coli, Staphylococcus spp., Enterococcus spp., and anaerobes. We also observed a significant decreased of the time to detection, with the mean and median in the post-lytic phase of 17.68 and 13.05 h compared with 19.49 and 14.47 h in the pre-lytic phase. Whereas the time to detection was the same for organisms recovered in the aerobic Plus bottles for both time periods, time to detection for the anaerobic lytic bottles was significantly faster than with the anaerobic Plus bottles. This study carried out on a long time observation reported that a simple modification of composition of blood culture set could lead to better results in bloodstream infection detection. [ABSTRACT FROM AUTHOR]

Viruses are the most abundant microorganisms in marine environments and viral infections can be either lytic (virulent) or lysogenic (temperate phage) within the host cell. The aim of this study was to quantify viral dynamics (abundance and infection) in the coastal Red Sea, a narrow oligotrophic basin with high surface water temperatures (22–32 °C degrees), high salinity (37.5–41) and continuous high insolation, thus making it a stable and relatively unexplored environment. We quantified viral and environmental changes in the Red Sea (two years) and the occurrence of lysogenic bacteria (induced by mitomycin C) on the second year. Water temperatures ranged from 24.0 to 32.5 °C, and total viral and bacterial abundances ranged from 1.5 to 8.7 × 106 viruses mL−1 and 1.9 to 3.2 × 105 bacteria mL−1, respectively. On average, 12.24% ± 4.8 (SE) of the prophage bacteria could be induced by mitomycin C, with the highest percentage of 55.8% observed in January 2018 when bacterial abundances were low; whereas no induction was measurable in spring when bacterial abundances were highest. Thus, despite the fact that the Red Sea might be perceived as stable, warm and saline, relatively modest changes in seasonal conditions were associated with large swings in the prevalence of lysogeny.

The goal of this study was to isolate and characterize phages that might be used in transport and treatment of potential E.coli pathogen in water sources. E.coli KP005067 was especially targeted because this is the dominant strain obtained from the sewage canal. The abundance of phage and its host directly from the sewage water was analysed using Epifluorescence Microscopy. The morphological characterization of the bacteriophages was studied using transmission electronic microscopy (TEM) and the genomic studies using Agarose Gel Electrophoresis. Studies on phage growth curve and its survival rate with respect to UV irradiation was also carried out. Almost 64% of the phages produced large, clear plaques indicating lytic activity. Phages had long noncontractile tail and icosahedral capsid head and therefore belonged to the Siphoviridae. Their estimated genome sizes was about 31 kb. One-step growth kinetics of the phage showed the latent period 15 min, rise period 20 min, and the average burst size 35 phage particles/infected cell. Also a clear downward trend in lytic activity was observed in phage groups exposed to longer than 30 minutes of UV. The characterization of the phages will be helpful in its future application as microbial tracers and bio-disinfectants in water sources.

Herpesviruses usurp host cell protein synthesis machinery to convert viral mRNAs into proteins, and the endoplasmic reticulum (ER) to ensure the proper folding, post-translational modification and trafficking of secreted and transmembrane viral proteins. Overloading the ER folding capacity activates the unfolded protein response (UPR), whereby sensor proteins, ATF6, PERK and IRE1, initiate a stress-mitigating transcription program that accelerates the catabolism of misfolded proteins, while increasing the ER folding capacity. Kaposi’s sarcoma-associated herpesvirus (KSHV) can be reactivated from latency through the chemical induction of ER stress, which causes an accumulation of the XBP1s transcription factor that transactivates the viral RTA lytic switch gene. The presence of XBP1s-responsive elements in the RTA promoter suggests that KSHV evolved a mechanism to respond to ER stress. Here, we report that ATF6, PERK and IRE1 were activated upon reactivation from latency and were required for efficient KSHV lytic replication. The genetic or pharmacologic inhibitions of each UPR sensor reduced virion production. Despite UPR sensor activation during KSHV lytic replication, downstream UPR transcriptional responses were restricted: (1) ATF6 was cleaved to activate the ATF6(N) transcription factor but ATF6(N)-responsive genes were not transcribed; (2) PERK phosphorylated eIF2, but ATF4 did not accumulate; (3) IRE1 caused XBP1–mRNA splicing, but the XBP1s protein did not accumulate and the XBP1s-responsive genes were not transcribed. The complementation of XBP1s deficiency during KSHV lytic replication inhibited virion production in a dose-dependent manner in epithelial cells. Taken together, these findings indicate that, while XBP1s plays an important role in reactivation from latency, it can inhibit virus replication at a later step, which the virus overcomes by preventing its synthesis. These findings suggest that KSHV hijacks UPR sensors to promote efficient viral replication while sustaining ER stress.

When phage infect their bacterial hosts, they may either lyse the cell and generate a burst of new phage, or lysogenize the bacterium, incorporating the phage genome into it. Phage lysis/lysogeny strategies are assumed to be highly optimized, with the optimal tradeoff depending on environmental conditions. However, in nature, phage of radically different lysis/lysogeny strategies coexist in the same environment, preying on the same bacteria. How can phage preying on the same bacteria coexist if one is more optimal than the other? Here, we address this conundrum within a modeling framework, simulating the population dynamics of communities of phage and their lysogens. We find that coexistence between phage of different lysis/lysogeny strategies is a natural outcome of chaotic population dynamics that arise within sufficiently diverse communities, which ensure no phage is able to absolutely dominate its competitors. Our results further suggest a bet-hedging mechanism at the level of the phage pan-genome, wherein obligate lytic (virulent) strains typically outcompete temperate strains, but also more readily fluctuate to extinction within a local community., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Since Salmonella Enteritidis is one of the major foodborne pathogens, on-site applicable rapid detection methods have been required for its control. The purpose of this study was to isolate and purify S. Enteritidis-specific phage (KFS-SE2 phage) from an eel farm and to investigate its feasibility as a novel, efficient, and reliable bio-receptor for its employment. KFS-SE2 phage was successfully isolated at a high concentration of (2.31 ± 0.43) × 1011 PFU/ml, and consisted of an icosahedral head of 65.44 ± 10.08 nm with a non-contractile tail of 135.21 ± 12.41 nm. The morphological and phylogenetic analysis confirmed that it belongs to the Pis4avirus genus in the family of Siphoviridae. KFS-SE2 genome consisted of 48,608 bp with 45.7% of GC content. Genome analysis represented KFS-SE2 to have distinctive characteristics as a novel phage. Comparative analysis of KFS-SE2 phage with closely related strains confirmed its novelty by the presence of unique proteins. KFS-SE2 phage exhibited excellent specificity to S. Enteritidis and was stable under the temperature range of 4 to 50°C and pH of 3 to 11 (P < 0.05). The latent time was determined to be 20 min. Overall, a new lytic KFS-SE2 phage was successfully isolated from the environment at a high concentration and the excellent feasibility of KFS-SE2 phage was demonstrated as a new bio-receptor for S. Enteritidis detection. [ABSTRACT FROM AUTHOR]

Bacteriophages (phages/viruses) need host bacteria to replicate and propagate. Primarily, a bacteriophage contains a head/capsid to encapsidate the genetic material. Some phages contain tails. Phages encode endolysins to hydrolyze bacterial cell wall. The two main classes of phages are lytic or virulent and lysogenic or temperate. In comparison with antibiotics, to deal with bacterial infections, phage therapy is thought to be more effective. In 1921, the use of phages against bacterial infections was first demonstrated. Later on, in humans, phage therapy was used to treat skin infections caused by Pseudomonas species. Furthermore, phages were successfully employed against infections in animals – calves, lambs, and pigs infected with Escherichia coli. In agriculture, for instance, phages have successfully been used e.g., Apple blossom infection, caused by Erwinia amylovora, was effectively catered with the use of bacteriophages. Bacteriophages were also used to control E. coli, Salmonella, Listeria, and Campylobacter contamination in food. Comparatively, phage display is a recently discovered technology, whereby, bacteriophages play a significant role. This review is an effort to collect almost recent and relevant information regarding applications and complications associated with the use of bacteriophages. [ABSTRACT FROM AUTHOR]

Awareness of risk factors associated with impending fracture and its radiologic appearance allows early diagnosis, supports prophylactic surgical treatment, and prevents the multiple complications of a pathologic fracture. Because the femur is the most common long bone affected by metastatic bone lesions, we address this clinically relevant site in this review. The key to early detection of risky bone lesions is familiarity with the possible clinical presentation, biomechanical effects of the anatomical site (femoral head and neck, intertrochanteric zone, proximal diaphysis), and the lesion types (lytic, blastic, or mixed). Awareness of the possible treatment strategies depending on the characteristics just listed allows high-quality targeted reporting. [ABSTRACT FROM AUTHOR]

Abstract: A 20‐month‐old female spayed Staffordshire Terrier (22.3 kg) presented to the Orthopedic Surgery Service at North Carolina State University Veterinary Teaching Hospital for evaluation of a 6‐week history of toe‐touching to nonweight‐bearing lameness in the right hind limb. Radiographs of the right stifle revealed a multiloculated lytic lesion of the distal femur, with a large open lytic zone centrally, numerous osseous septations peripherally, and focal areas of cortical thinning and loss. An aspirate of the right distal femoral lesion yielded mildly cloudy serosanguineous fluid. Cytologic examination of the fluid revealed a pleomorphic population of discrete cells that exhibited marked anisocytosis and anisokaryosis and a variable nuclear‐to‐cytoplasmic (N:C) ratio, which were interpreted as probable neoplastic cells, with few macrophages, and evidence of hemorrhage. Given the clinical signs of pain, lesion size, and concern for malignant neoplasia, amputation of the right hind limb was performed. Histologically, the lesion had undulating walls 1‐3 mm thick with a continuous outer layer of dense fibrous tissue and an inner layer composed of reactive cancellous bone with no cortical compacta remaining. Remnants of thin fibrous or fibro‐osseous septa projected from the bony wall into the cyst lumen. The final histologic diagnosis was a benign multiloculated solitary (unicameral) bone cyst of the distal right femur. Based on the histopathologic findings, it was speculated that the cells identified on cytology were a mixture of developing osteoclasts, osteoblasts, endothelial, and stromal cells. This is the first report describing the cytologic examination of a solitary bone cyst in veterinary medicine. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) productive replication in vitro is most often studied in fibroblasts. In vivo, fibroblasts amplify viral titers, but transmission and pathogenesis require the infection of other cell types, most notably epithelial cells. In vitro, the study of HCMV infection of epithelial cells has been almost exclusively restricted to ocular epithelial cells. Here we present oral epithelial cells with relevance for viral interhost transmission as an in vitro model system to study HCMV infection. We discovered that HCMV productively replicates in normal oral keratinocytes (NOKs) and telomerase-immortalized gingival cells (hGETs). Our work introduces oral epithelial cells for the study of HCMV productive infection, drug screening, and vaccine development. [ABSTRACT FROM AUTHOR]

Background: Cribriform lysis has been considered a contraindication for topical treatment of sinonasal aspergillosis (SNA) because of concerns about drug extravasation with resultant neurologic signs or death. Objective/Hypothesis: To describe dogs with SNA and cribriform plate lysis treated with topical antifungal medications. Our hypothesis was that the conventional dogma that topical therapy should be avoided in these cases is incorrect. Animals: Nine client‐owned dogs with SNA and lysis of the cribriform plate, lysis of the floor of a frontal sinus or both detected by computed tomography (CT). Methods: A retrospective review of medical records was performed. Dogs that met inclusion criteria (ie, SNA confirmed by at least 1 laboratory test, braincase affected on CT, and topical treatment applied) were included. Size of lesions, ancillary diagnostic test results, topical therapy, and adjuvant PO treatments were recorded. Outcome was determined by phone calls. Results: Four dogs were alive at the time of the manuscript submission with follow‐up ranging from 188 to 684 days without neurological signs observed. All dogs were discharged without major complication 1‐7 days postoperatively. One dog that had presented with a history of seizures experienced seizure activity 2 months after treatment. Conclusions and Clinical Importance: Topical therapy did not result in complications in these dogs in which lytic regions as large as 16 × 22 mm2 were noted. Sinonasal aspergillosis associated lysis of the cribriform plate; lysis of the floor of a frontal sinus or both detected on CT is not necessarily a contraindication to topical therapy. [ABSTRACT FROM AUTHOR]

In recent years, coral associated viruses could play primal role in protecting coral health, yet their ecological traits are poorly investigated. In this study, the abundance and life cycles (lysogeny and lytic) of viruses associated with contrasted coral health states (healthy and bleached) were studied and compared. In addition, the density of bacteria and Symbiodium were also be determined by epifluorescence microscopy. The results showed that viral abundance increased 1.2 times and bacterial abundance decreased 0.6 times in healthy corals compared to bleached ones. The number of Symbiodinium significantly reduced 5.6 times in bleached corals compared to healthy corals. One of the most important results in this study was the coexistence of the both lysogenic and lytic viruses in healthy coral. The fraction of lysogenic bacteria was 2 times higher in healthy corals than in bleached ones. Healthy corals carried 3.5-fold more viral production than the diseased ones. Overall, the results showed that, in healthy state, corals might be a favorable environment for viral infection, promoting the development of both temperate and virulent phages. This coexistence might be crucial for coral viability through the complex links with their coral-associated bacterial hosts. [ABSTRACT FROM AUTHOR]

Objectives: To compare the concordance between fine-needle aspiration and core biopsies for osseous lesions by lesion imaging appearance and CT attenuation.Materials and methods: Retrospective review of 215 FNAs of osseous lesions performed in conjunction with core biopsy at our institution over a 6-year period (2011-2016). FNAs were interpreted independently of core biopsies. We assessed if FNA in conjunction with core biopsy increased diagnostic accuracy compared to core biopsy alone. We also calculated the concordance between FNA and core biopsy by lesion appearance, lesion CT attenuation, lesion histology, lesion location and FNA needle gauge size.Results: Core biopsy alone provided the diagnosis in 207/215 cases (96.3%), however, the FNA provided the diagnosis in the remaining 8/215 cases (3.7%) where the core biopsy was non-diagnostic. There were 154 (71.6%) lytic lesions, 21 (9.8%) blastic lesions, 25 (11.6%) mixed lytic and blastic lesions and 15 (7.0%) lesions that were neither lytic nor blastic. The concordance between FNA and core biopsy for lytic osseous lesions (136/154 cases, 88.3%) was statistically significantly higher than that for blastic osseous lesions (13/21 cases, 61.9%) [P = 4.2 × 10−3; 95% CI (0.02, 0.50)]. The concordance between FNA and core biopsy was higher for low-attenuation- (110/126) than high-attenuation (58/77) lesions (P = 0.028). The concordance between FNA and core biopsy was also higher for metastases (102/119 cases, 85.7%) than non-metastases (78/96, 81.3%) [P = 0.487; 95% CI (− 0.15, 0.065)]. There was no difference in the rate of concordance between FNA and core biopsy by lesion location or FNA needle gauge size (P > 0.05).Conclusion: FNA with core biopsy increases diagnostic rate compared to core biopsy alone or FNA alone. The concordance between FNA and core biopsy is higher for lytic lesions than for blastic lesions; and higher for low-attenuation lesions than for high-attenuation lesions. [ABSTRACT FROM AUTHOR]

Viruses in aquatic environments play a key role in microbial population dynamics and nutrient cycling. In particular, bacteria of the phylum Bacteriodetes are known to participate in recycling algal blooms. Studies of phage−host interactions involving this phylum are hence important to understand the processes shaping bacterial and viral communities in the ocean as well as nutrient cycling. In this study, we isolated and sequenced three strains of flavobacteria—LMO6, LMO9, LMO8—and 38 virulent phages infecting them. These phages represent 15 species, occupying three novel genera. Additionally, one temperate phage was induced from LMO6 and was found to be competent at infecting LMO9. Functions could be predicted for a limited number of phage genes, mainly representing roles in DNA replication and virus particle formation. No metabolic genes were detected. While the phages isolated on LMO8 could infect all three bacterial strains, the LMO6 and LMO9 phages could not infect LMO8. Of the phages isolated on LMO9, several showed a host-derived reduced efficiency of plating on LMO6, potentially due to differences in DNA methyltransferase genes. Overall, these phage−host systems contribute novel genetic information to our sequence databases and present valuable tools for the study of both virulent and temperate phages.

In this paper, we consider the evolutionary competition between budding and lytic viral release strategies, using a delay differential equation model with distributed delay. When antibody is not established, the dynamics of competition depends on the respective basic reproductive ratios of the two viruses. If the basic reproductive ratio of budding virus is greater than that of lytic virus and one, budding virus can survive. When antibody is established for both strains but the neutralization capacities are the same for both strains, consequence of the competition also depends only on the basic reproductive ratios of the budding and lytic viruses. Using two concrete forms of the viral production functions, we are also able to conclude that budding virus will outcompete if the rates of viral production, death rates of infected cells and neutralizing capacities of the antibodies are the same for budding and lytic viruses. In this case, budding strategy would have an evolutionary advantage. However, if the antibody neutralization capacity for the budding virus is larger than that for the lytic virus, the lytic virus can outcompete the budding virus provided that its reproductive ratio is very high. An explicit threshold is derived.

As the "kidneys of the Earth", wetlands play important roles as biodiversity reservoirs, in water purification, and in flood control. In this study, 2 lytic cold-active bacteriophages, named VW-6S and VW-6B, infecting Pseudomonas fluorescens W-6 cells from the Napahai plateau wetland in China were isolated and characterized. Electron microscopy showed that both VW-6S and VW-6B had an icosahedral head (66.7 and 61.1 nm, respectively) and a long tail (8.3 nm width x 233.3 nm length and 11.1 nm width x 166.7 nm length, respectively). The bacteriophages VW-6S and VW-6B were classified as Siphoviridae and had an approximate genome size of 30-40 kb. The latent and burst periods of VW-6S were 60 and 30 min, whereas those of VW-6B were 30 and 30 min, respectively. The optimal pH values for the bacteriophages VW-6S and VW-6B were 8.0 and 10.0, respectively, and their activity decreased rapidly at temperatures higher than 60 °C. These cold-active bacteriophages provide good materials for further study of cold-adaptation mechanisms and interaction with the host P. fluorescens. [ABSTRACT FROM AUTHOR]

Cell death is a fundamental biological phenomenon that is essential for the survival and development of an organism. Emerging evidence also indicates that cell death contributes to immune defense against infectious diseases. Pyroptosis is a form of inflammatory programmed cell death pathway activated by human and mouse caspase-1, human caspase-4 and caspase-5, or mouse caspase-11. These inflammatory caspases are used by the host to control bacterial, viral, fungal, or protozoan pathogens. Pyroptosis requires cleavage and activation of the pore-forming effector protein gasdermin D by inflammatory caspases. Physical rupture of the cell causes release of the pro-inflammatory cytokines IL-1β and IL-18, alarmins and endogenous danger-associated molecular patterns, signifying the inflammatory potential of pyroptosis. Here, we describe the central role of inflammatory caspases and pyroptosis in mediating immunity to infection and clearance of pathogens. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) was first discovered in 1964, and was the first known human tumor virus now shown to be associated with a vast number of human diseases. Numerous studies have been conducted to understand infection, propagation and transformation in various cell types linked to human diseases. However, a comprehensive lens through which virus infection, reactivation and transformation of infected host cells can be visualized is yet to be formally established and will need much further investigation. Several human cell types infected by EBV have been linked to associated diseases. However, whether these are a direct result of EBV infection or indirectly due to contributions by additional infectious agents will need to be fully investigated. Therefore, a thorough examination of infection, reactivation and cell transformation induced by EBV will provide a more detailed view of its contributions that drive pathogenesis. This undoubtedly expand our knowledge of the biology of EBV infection and the signaling activities of targeted cellular factors dysregulated on infection. Furthermore, these insights may lead to identification of therapeutic targets and agents for clinical interventions. Here we review the spectrum of EBV-associated diseases, the role of the encoded latent antigens, and the switch to latency or lytic replication which occurs in EBV infected cells. Furthermore, we describe the cellular processes and critical factors which contribute to cell transformation. We also describe the fate of B-cells and epithelial cells after EBV infection and the expected consequences which contribute to establishment of viral-associated pathologies.

A lytic bacteriophage PHB01 specific for Pasteurella multocida type D was isolated from the sewage water collected from a pig farm. This phage had the typical morphology of the family Podoviridae, order Caudovirales, presenting an isometric polyhedral head and a short noncontractile tail. PHB01 was able to infect most of the non-toxigenic P. multocida type D strains tested, but not toxigenic type D strains and those belonging to other capsular types. Phage PHB01, the first lytic phage specific for P. multocida type D sequenced thus far, presents a 37,287-bp double-stranded DNA genome with a 223-bp terminal redundancy. The PHB01 genome showed the highest homology with that of PHB02, a lytic phage specific for P. multocida type A. Phylogenetic analysis showed that PHB01 and PHB02 were composed of a genus that was close to the T7-virus genus. In vivo tests using mouse models showed that the administration of PHB01 was safe to the mice and had a good effect on treating the mice infected with different P. multocida type D strains including virulent strain HN05. These findings suggest that PHB01 has a potential use in therapy against infections caused by P. multocida type D.

Giant cell reparative granulomas (GCRG) often affect the bones of the hands and the feet. Treatment of this lesion depends on the exact location and amount of localized bony destruction. Ours is the first case report to discuss the nuances of treating this lesion in the thumb distal phalanx. A 19-year-old male presented with lytic, destructive expansion of his left thumb distal phalanx; imaging was suggestive of an aneurysmal bone cyst. Open biopsy was interpreted as giant cell reparative granuloma. Curettage and bone grafting resulted in complete healing of the distal phalanx with an excellent range of motion and interphalangeal joint stability. GCRG is a rare, benign entity typically presenting as a lytic bone lesion. Despite the initial massive bony destruction, this lesion nevertheless healed with curettage and bone grafting with maintained flexor pollicis longus and extensor pollicis longus function, permitting excellent active motion postoperatively., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Arvind et al.)

The goal of this study was to isolate and characterize phages that might be used in transport and treatment of potential E.coli pathogen in water sources. E.coli KP005067 was especially targeted because this is the dominant strain obtained from the sewage canal. The abundance of phage and its host directly from the sewage water was analysed using Epifluorescence Microscopy. The morphological characterization of the bacteriophages was studied using transmission electronic microscopy (TEM) and the genomic studies using Agarose Gel Electrophoresis. Studies on phage growth curve and its survival rate with respect to UV irradiation was also carried out. Almost 64% of the phages produced large, clear plaques indicating lytic activity. Phages had long noncontractile tail and icosahedral capsid head and therefore belonged to the Siphoviridae. Their estimated genome sizes was about 31 kb. One-step growth kinetics of the phage showed the latent period 15 min, rise period 20 min, and the average burst size 35 phage particles/infected cell. Also a clear downward trend in lytic activity was observed in phage groups exposed to longer than 30 minutes of UV. The characterization of the phages will be helpful in its future application as microbial tracers and bio-disinfectants in water sources. [ABSTRACT FROM AUTHOR]

Wetlands are often called the 'kidneys of the Earth' and contribute substantially to environmental improvement. Pseudomonas fluorescens is a major contaminant of milk products and causes the spoilage of refrigerated foods and fresh poultry. In this study, we isolated and characterized a lytic cold-active bacteriophage named VSW-3 together with P. fluorescens SW-3 cells from the Napahai wetland in China. Electron microscopy showed that VSW-3 had an icosahedral head (56 nm) and a tapering tail (20 nm × 12 nm) and a genome size of approximate 40 kb. On the basis of the top-scoring hits in the BLASTP analysis, VSW-3 showed a high degree of module similarity to the Pseudomonas phages Andromeda and Bf7. The latent and burst periods were 45 and 20 min, respectively, with an average burst size of 90 phage particles per infected cell. The pH and thermal stability of VSW-3 were also explored. The optimal pH was found to be 7.0 and the activity decreased rapidly when the temperature exceeded 60 °C. VSW-3 is a cold-active bacteriophage, hence, it is important to research its ability to prevent product contamination caused by P. fluorescens and to characterize its relationship with its host P. fluorescens in the future. [ABSTRACT FROM AUTHOR]

Soil and plant samples from black rot infected fields were processed to isolate wild type Xanthomonas campestris pv. campestris (Xcc) bacteriophages by overlay agar method. Various Xcc strains were employed as indicator hosts. The aim of this study was to isolate and purify potential bacteriophages for their ability to lyse plant pathogenic strains of Xcc in vitro. Bacteriophages were purified and selected for further characterization based on their ability to produce clear lysis on plaque assay. Seventeen strains of pathogenic Xcc were tested for sensitivity to 31 phages isolated during the study. Lysis was graded subjectively as per standard. A virulent phage Xcc9SH3 isolated from soil sample from Lucknow was found to lyse all tested strains of Xcc in vitro. Characterization of Xcc9SH3 was done based on plaque morphology, phage titre, organic solvent sensitivity, effect of temperature and transmission electron microscopy. The size of long noncontractile tail of the phage was 100 nm in length and 10 nm in width with 20 nm diameter of head. The isometric head of the phage predicted to belong to Siphoviridae (dsDNA viruses) family of bacteriophages. These phages may be useful tool in specific and efficient detection and control of Xcc causing black rot disease in cole crops. [ABSTRACT FROM AUTHOR]

ABSTRACT Clostridium difficile has emerged as a major cause of infectious diarrhea in hospitalized patients, with increasing mortality rate and annual healthcare costs exceeding $3 billion. Since C. difficile infections are associated with the use of antibiotics, there is an urgent need to develop treatments that can inactivate the bacterium selectively without affecting commensal microflora. Lytic enzymes from bacteria and bacteriophages show promise as highly selective and effective antimicrobial agents. These enzymes often have a modular structure, consisting of a catalytic domain and a binding domain. In the current work, using consensus catalytic domain and cell-wall binding domain sequences as probes, we analyzed in silico the genome of C. difficile, as well as phages infecting C. difficile. We identified two genes encoding cell lytic enzymes with possible activity against C. difficile. We cloned the genes in a suitable expression vector, expressed and purified the protein products, and tested enzyme activity in vitro. These newly identified enzymes were found to be active against C. difficile cells in a dose-dependent manner. We achieved a more than 4-log reduction in the number of viable bacteria within 5 h of application. Moreover, we found that the enzymes were active against a wide range of C. difficile clinical isolates. We also characterized the biocatalytic mechanism by identifying the specific bonds cleaved by these enzymes within the cell wall peptidoglycan. These results suggest a new approach to combating the growing healthcare problem associated with C. difficile infections. Biotechnol. Bioeng. 2016;113: 2568-2576. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The performance of 3 blood culture bottles (BACTEC Plus Aerobic/F, Plus Anaerobic/F, and Anaerobic Lytic/F) were analyzed with clinical specimens collected from 688 Emergency Department patients. A total of 270 strains belonging to 33 species were identified, with E. coli and S. aureus as the most frequently detected. Overall recovery rate (RR) of bacteria and yeast was equivalent in the Plus Aerobic/F vials (208 of 270 isolates; 77.0%) and Anaerobic Lytic/F vials (206 isolates; 76.3%) and significantly better than in the Plus Anaerobic/F vials (189 isolates; 70.0%). Median time to detection (TTD) was earliest with the Anaerobic Lytic/F vials (12.0 h) compared with the Plus Aerobic/F (14.6 h) and Plus Anaerobic/F vials (15.4 h). Positivity rate (PR) was similar for Anaerobic Lytic/F vials (76.9%) and Plus Aerobic/F vials (76.5%), but better if compared with Plus Anaerobic/F vials (69.4%). The PR and TTD for the combination of Plus Aerobic/F with Anaerobic Lytic/F (94.5% and 12.3 h, respectively) was significantly better than with Plus Aerobic/F with Plus Anaerobic/F (87.8% and 14.1 h). [ABSTRACT FROM AUTHOR]

Epstein--Barr virus (EBV) was first discovered in 1964, and was the first known human tumor virus now shown to be associated with a vast number of human diseases. Numerous studies have been conducted to understand infection, propagation, and transformation in various cell types linked to human diseases. However, a comprehensive lens through which virus infection, reactivation and transformation of infected host cells can be visualized is yet to be formally established and will need much further investigation. Several human cell types infected by EBV have been linked to associated diseases. However, whether these are a direct result of EBV infection or indirectly due to contributions by additional infectious agents will need to be fully investigated. Therefore, a thorough examination of infection, reactivation, and cell transformation induced by EBV will provide a more detailed view of its contributions that drive pathogenesis. This undoubtedly expand our knowledge of the biology of EBV infection and the signaling activities of targeted cellular factors dysregulated on infection. Furthermore, these insights may lead to identification of therapeutic targets and agents for clinical interventions. Here, we review the spectrum of EBV-associated diseases, the role of the encoded latent antigens, and the switch to latency or lytic replication which occurs in EBV infected cells. Furthermore, we describe the cellular processes and critical factors which contribute to cell transformation. We also describe the fate of B-cells and epithelial cells after EBV infection and the expected consequences which contribute to establishment of viral-associated pathologies. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus and human papillomaviruses are human tumor viruses that infect and replicate in upper aerodigestive tract epithelia and cause head and neck cancers. The productive phases of both viruses are tied to stratified epithelia highlighting the possibility that these viruses may affect each other's life cycles. Our lab has established an in vitro model system to test the effects of EBV and HPV co-infection in stratified squamous oral epithelial cells. Our results indicate that HPV increases maintenance of the EBV genome in the co-infected cells and promotes lytic reactivation of EBV in upper layers of stratified epithelium. Expression of the HPV oncogenes E6 and E7 were found to be necessary and sufficient to account for HPV-mediated lytic reactivation of EBV. Our findings indicate that HPV increases the capacity of epithelial cells to support the EBV life cycle, which could in turn increase EBV-mediated pathogenesis in the oral cavity. [ABSTRACT FROM AUTHOR]

Intraosseous nerve sheath tumors are very rare tumors accounting for lesser than 0.2% of primary bone tumors. We present an 18-year-old female who presented with left facial paresis for the last 1 year. Magnetic resonance imaging (MRI) demonstrated expansile, multiseptated, enhancing bony lesion in the left petrous apex. There was also abnormal enhancement of the 7-8th nerve complex within the internal auditory canal. Tumor was excised by subtemporal extradural approach. The lesion was diagnosed as intraosseous neurothekeoma on histopathology. This is an extremely rare tumor and its MRI appearance in this location is being described for the first time in literature.