PeerJ Preprints: Immunologyhttps://peerj.com/preprints/index.atom?journal=peerj&subject=5100Immunology articles published in PeerJ PreprintsGene/environment interaction and autoimmune diseasehttps://peerj.com/preprints/279392019-09-052019-09-05Tamia A HarrisShai Bel
Autoimmune diseases are complex illnesses in which the body’s immune system attacks its own healthy tissues. These diseases, which can be fatal, gravely impact the quality of life of those afflicted by them with no cure currently available. The exact etiology of autoimmune diseases is not completely clear. Biomedical research has revealed that both genetic and environmental factors contribute to the development and progression of these diseases. Nevertheless, genetic and environmental factors alone cannot explain a large proportion of cases, leading to the possibility that the two factors interact in driving disease onset. Understanding how genetic and environmental factor influence host physiology in a manner that leads to the development of autoimmune diseases can reveal the mechanisms by which these diseases manifest, and bring us closer to finding a cure for them. In this chapter, we will review the current research of genetic/environmental interactions that contribute to development of autoimmune diseases, with an emphasis on interactions between the host and the multitudes of microbes that inhabit it, the microbiota.
Autoimmune diseases are complex illnesses in which the body’s immune system attacks its own healthy tissues. These diseases, which can be fatal, gravely impact the quality of life of those afflicted by them with no cure currently available. The exact etiology of autoimmune diseases is not completely clear. Biomedical research has revealed that both genetic and environmental factors contribute to the development and progression of these diseases. Nevertheless, genetic and environmental factors alone cannot explain a large proportion of cases, leading to the possibility that the two factors interact in driving disease onset. Understanding how genetic and environmental factor influence host physiology in a manner that leads to the development of autoimmune diseases can reveal the mechanisms by which these diseases manifest, and bring us closer to finding a cure for them. In this chapter, we will review the current research of genetic/environmental interactions that contribute to development of autoimmune diseases, with an emphasis on interactions between the host and the multitudes of microbes that inhabit it, the microbiota.Allogenic stem cell transplant in a patient with classical Kaposi's sarcomahttps://peerj.com/preprints/482019-08-042019-08-04Richard Barchas
A 68 year old male with a history of classical Kaposi's sarcoma (KS) and precursor T-cell acute lymphoblastic leukemia (ALL) received an allogenic stem cell transplant from an unrelated donor to treat his ALL. He developed acute graft-vs.-host-disease (GVHD) which was treated by increasing immunosuppressants. KS, which had been in remission for years, then recurred aggressively. Tapering immunosuppressants to treat the KS was not possible because of GVHD. Chemotherapy could not be used because of its adverse effect on the bone marrow so soon after transplant. The only option was to use antiviral therapy (cidofovir) to lower the level of HHV-8, the virus that is a causal factor in KS. Although HHV-8 levels were significantly reduced, new KS lesions continued to appear. The patient developed acute kidney injury after the third cidofovir infusion and died from renal and respiratory failure soon afterward. Post-mortem revealed extensive internal KS lesions involving multiple organs. Based on the experience with this patient, allogenic transplant using an unrelated donor has been found to be a questionable treatment modality for classical KS patients requiring treatment for another condition such as leukemias and lymphomas. Post-transplant immunosuppression is required to prevent GVHD, and if it occurs, immunosuppression may have to be increased. Aggressive KS developed in this patient under these conditions, and could not be controlled by tapering immunosuppressants. Although the risk of GVHD is lower for an allogenic transplant using a matched sibling instead of an unrelated donor, the risk of both GVHD and aggressive KS both developing may still be unacceptably high.Alternative treatment modalities for these patients might include continuing with chemotherapy and autologous transplant. These avoid GVHD and lower the need for long term immunosuppression, but have a much higher risk of relapse of the underlying malignancy. Still, they could be preferable to an allogenic transplant for such cases.
A 68 year old male with a history of classical Kaposi's sarcoma (KS) and precursor T-cell acute lymphoblastic leukemia (ALL) received an allogenic stem cell transplant from an unrelated donor to treat his ALL. He developed acute graft-vs.-host-disease (GVHD) which was treated by increasing immunosuppressants. KS, which had been in remission for years, then recurred aggressively. Tapering immunosuppressants to treat the KS was not possible because of GVHD. Chemotherapy could not be used because of its adverse effect on the bone marrow so soon after transplant. The only option was to use antiviral therapy (cidofovir) to lower the level of HHV-8, the virus that is a causal factor in KS. Although HHV-8 levels were significantly reduced, new KS lesions continued to appear. The patient developed acute kidney injury after the third cidofovir infusion and died from renal and respiratory failure soon afterward. Post-mortem revealed extensive internal KS lesions involving multiple organs. Based on the experience with this patient, allogenic transplant using an unrelated donor has been found to be a questionable treatment modality for classical KS patients requiring treatment for another condition such as leukemias and lymphomas. Post-transplant immunosuppression is required to prevent GVHD, and if it occurs, immunosuppression may have to be increased. Aggressive KS developed in this patient under these conditions, and could not be controlled by tapering immunosuppressants. Although the risk of GVHD is lower for an allogenic transplant using a matched sibling instead of an unrelated donor, the risk of both GVHD and aggressive KS both developing may still be unacceptably high.Alternative treatment modalities for these patients might include continuing with chemotherapy and autologous transplant. These avoid GVHD and lower the need for long term immunosuppression, but have a much higher risk of relapse of the underlying malignancy. Still, they could be preferable to an allogenic transplant for such cases.Shared TCR epitope cross-reactivity could permit dyads of Foxp3+ regulatory and IL-2-producing T cell precursors to escape thymic purgehttps://peerj.com/preprints/278532019-07-112019-07-11David UsharauliTirumalai Kamala
The thymus-derived Foxp3+ regulatory T cells (Tregs) represent a unique population of CD4+ T cells responsible for maintaining dominant tolerance to auto-antigens, beneficial microbiota and potential irritants such as allergens on the one hand and efficient but balanced defense against pathogens on the other. How Tregs with high-affinity TCRs for thymically expressed epitopes survive thymic deletion or display such broad functionality is presently unclear. We recently introduced a novel framework dubbed SPIRAL (SPecific ImmunoRegulatory ALgorithm) which suggests that antigen cross-reactivity of thymic Treg repertoire could provide a mechanistic basis for its broad functionality. Here we further develop this model to propose how escape of high-affinity Tregs from thymic purge could be achieved in dyads with high-affinity natural IL-2-producing T cells (IL-2p T cells) sharing TCR epitope cross-reactivity. We believe this interpretation could reconcile contradictions related to Treg ontogeny in the thymus and their role in modulating antigen-specific immune responses.
The thymus-derived Foxp3+ regulatory T cells (Tregs) represent a unique population of CD4+ T cells responsible for maintaining dominant tolerance to auto-antigens, beneficial microbiota and potential irritants such as allergens on the one hand and efficient but balanced defense against pathogens on the other. How Tregs with high-affinity TCRs for thymically expressed epitopes survive thymic deletion or display such broad functionality is presently unclear. We recently introduced a novel framework dubbed SPIRAL (SPecific ImmunoRegulatory ALgorithm) which suggests that antigen cross-reactivity of thymic Treg repertoire could provide a mechanistic basis for its broad functionality. Here we further develop this model to propose how escape of high-affinity Tregs from thymic purge could be achieved in dyads with high-affinity natural IL-2-producing T cells (IL-2p T cells) sharing TCR epitope cross-reactivity. We believe this interpretation could reconcile contradictions related to Treg ontogeny in the thymus and their role in modulating antigen-specific immune responses.Integrating the extracellular, intracellular, and intercellular metabolic processes of Escherichia coli through glucose saturation, inhibition of the acetyl-CoA carboxylase subunit accA with asRNA, and through quantifying cell to cell quorum-sensinghttps://peerj.com/preprints/274592019-07-032019-07-03Tatiana HillmanCory Tobin
The study aims to demonstrate the link between bacterial cell metabolism and virulence through integrating the environmental, genetic, and cell to cell signaling molecular processes. Dietary fiber metabolized into glucose, increases the proliferation of intestinal microflora, which augments the outputof the Short Chain Fatty Acids. Bacteria ferment the glucose, from fiber, into Short Chain Fatty Acids, which help regulate many biochemical processes and pathways. Each SCFA maintains colonic pH, promotes cell differentiation, and the apoptosis of colonocytes. To model a high-fiber diet, increasing the synthesis of Acetyl-CoA carboxylase, an enzyme that catabolizes glucose into SCFAs, Escherichia coli was cultured in Luria Broth enhanced with a high to low concentration of glucose. The 15mM, a high concentration of glucose, yielded qPCR products measured, for the target gene accA, which was 4,210ng/µL. The 7.5mM sample produced a concentration equaled to 375 ng/µL, and the 0µM sample measured an accA concentration of 196 ng/µL. The gene accA, 1 of 4 subunits for the Acetyl-CoA Carboxylase enzyme, was suppressed by asRNA, producing a qPCR concentration of 63ng/µL. Antisense RNA for accA reduced the amount of Lux-S, a vital gene needed for propagating quorum-sensing signal molecules. The Lux-S gene, responsible for releasing autoinducer 2 for cell to cell quorum sensing, was reduced by the gene inhibition of accA with asRNA. The increase in Lux-S transcription increases biofilm production for spreading virulence. The further implications of the study propose designing antibiotics that target bacterial cell metabolic processes to block bacterial antibiotic resistance.
The study aims to demonstrate the link between bacterial cell metabolism and virulence through integrating the environmental, genetic, and cell to cell signaling molecular processes. Dietary fiber metabolized into glucose, increases the proliferation of intestinal microflora, which augments the outputof the Short Chain Fatty Acids. Bacteria ferment the glucose, from fiber, into Short Chain Fatty Acids, which help regulate many biochemical processes and pathways. Each SCFA maintains colonic pH, promotes cell differentiation, and the apoptosis of colonocytes. To model a high-fiber diet, increasing the synthesis of Acetyl-CoA carboxylase, an enzyme that catabolizes glucose into SCFAs, Escherichia coli was cultured in Luria Broth enhanced with a high to low concentration of glucose. The 15mM, a high concentration of glucose, yielded qPCR products measured, for the target gene accA, which was 4,210ng/µL. The 7.5mM sample produced a concentration equaled to 375 ng/µL, and the 0µM sample measured an accA concentration of 196 ng/µL. The gene accA, 1 of 4 subunits for the Acetyl-CoA Carboxylase enzyme, was suppressed by asRNA, producing a qPCR concentration of 63ng/µL. Antisense RNA for accA reduced the amount of Lux-S, a vital gene needed for propagating quorum-sensing signal molecules. The Lux-S gene, responsible for releasing autoinducer 2 for cell to cell quorum sensing, was reduced by the gene inhibition of accA with asRNA. The increase in Lux-S transcription increases biofilm production for spreading virulence. The further implications of the study propose designing antibiotics that target bacterial cell metabolic processes to block bacterial antibiotic resistance.CRISPR-Cas9 may restore the balance of hormones affected by the frequency of DNA methylation sites and a decrease of commensal bacteriahttps://peerj.com/preprints/275092019-06-212019-06-21Tatiana Hillman
In this review, it is suggested that there are connections between hormonal changes, the frequency of DNA methylation, and disease. The commensal microbes of the gut may also affect the production of those hormones. Short Chain Fatty Acids, produced from gut microbiota glucose metabolism, like butyrate, propionate, folate, and acetate act as ligands that bind to G-coupled protein receptors. For example, folate from Bifidobacterium donates a methyl for synthesizing S-adenosylmethionine or SAM, which then donates a methyl to the enzymes of DNA methylation, acting as a substrate. The effects of hormones on DNA methylation was reviewed. Increased progesterone can produce breast cancer by lessening DNA methylation allowing progesterone molecules to bind DNA, amplifying gene expression. Through measuring the frequency of DNA methylation perhaps breast cancer can be more readily identified, diagnosed, and treated. The intended purpose for this review is to propose the possibility of applying CRISPR-Cas9 methods to correct and restore the balance of hormones through epigenetic means. In this review, 1) the effects of microbes on hormonal balance, 2) the connection between hormones and DNA Methylation, 3) cancer and DNA methylation, 4) measuring DNA methylation, and 5) applying CRISPR methods will be discussed.
In this review, it is suggested that there are connections between hormonal changes, the frequency of DNA methylation, and disease. The commensal microbes of the gut may also affect the production of those hormones. Short Chain Fatty Acids, produced from gut microbiota glucose metabolism, like butyrate, propionate, folate, and acetate act as ligands that bind to G-coupled protein receptors. For example, folate from Bifidobacterium donates a methyl for synthesizing S-adenosylmethionine or SAM, which then donates a methyl to the enzymes of DNA methylation, acting as a substrate. The effects of hormones on DNA methylation was reviewed. Increased progesterone can produce breast cancer by lessening DNA methylation allowing progesterone molecules to bind DNA, amplifying gene expression. Through measuring the frequency of DNA methylation perhaps breast cancer can be more readily identified, diagnosed, and treated. The intended purpose for this review is to propose the possibility of applying CRISPR-Cas9 methods to correct and restore the balance of hormones through epigenetic means. In this review, 1) the effects of microbes on hormonal balance, 2) the connection between hormones and DNA Methylation, 3) cancer and DNA methylation, 4) measuring DNA methylation, and 5) applying CRISPR methods will be discussed.A review: Possible optimization of Cas9-sgRNA nuclease delivery via ingested lipid nanoparticles bioencapsulated within plant cell-based enfoldinghttps://peerj.com/preprints/277092019-06-072019-06-07Tatiana Hillman
The possibility of gene editing to correct disorders is one of the most impactful therapeutic agents, currently. CRISPR Cas9-sgRNA nucleases can be used to cleave and to delete harmful or pathogenic DNA sequences, which cause genetic disorders. Cas9 nuclease with palindromic repeats can cut and delete a single point mutation or multiple DNA target site sequences. The Cas9, attached to a sgRNA or a guiding RNA, finds and then cleaves the target DNA sequence. The Cas9-sgRNA method of cleavage has corrected DNA mutations that cause cataracts in the eyes, cystic fibrosis, and chronic granulomatous disease. However, there are issues for producing a less strenuous delivery of Cas9-sgRA to target DNA sequences. Delivering Cas-9 nucleases are negatively affected by off-target DNA sites, sgRNA design, off-target cleavage, Cas9 activation, and the method of delivery. This review focuses on oral and ingested delivery methods to effectively guide the transport of Cas9-sgRNA nucleases in vivo. A review of Cas9 delivery will present possible alternatives for nuclease delivery within optimized lipid-nanoparticles, plant, algae, and bacterial-based orally ingested edibles. This review will attempt to provide evidence in support of enhancing the Cas9 delivery through therapeutic bioencapsulated ingestion. In this review, it is suggested that the ingestion of encapsulated edibles carrying the nuclease can more directly target cells within the gastrointestinal tract for blood or lymph circulation.
The possibility of gene editing to correct disorders is one of the most impactful therapeutic agents, currently. CRISPR Cas9-sgRNA nucleases can be used to cleave and to delete harmful or pathogenic DNA sequences, which cause genetic disorders. Cas9 nuclease with palindromic repeats can cut and delete a single point mutation or multiple DNA target site sequences. The Cas9, attached to a sgRNA or a guiding RNA, finds and then cleaves the target DNA sequence. The Cas9-sgRNA method of cleavage has corrected DNA mutations that cause cataracts in the eyes, cystic fibrosis, and chronic granulomatous disease. However, there are issues for producing a less strenuous delivery of Cas9-sgRA to target DNA sequences. Delivering Cas-9 nucleases are negatively affected by off-target DNA sites, sgRNA design, off-target cleavage, Cas9 activation, and the method of delivery. This review focuses on oral and ingested delivery methods to effectively guide the transport of Cas9-sgRNA nucleases in vivo. A review of Cas9 delivery will present possible alternatives for nuclease delivery within optimized lipid-nanoparticles, plant, algae, and bacterial-based orally ingested edibles. This review will attempt to provide evidence in support of enhancing the Cas9 delivery through therapeutic bioencapsulated ingestion. In this review, it is suggested that the ingestion of encapsulated edibles carrying the nuclease can more directly target cells within the gastrointestinal tract for blood or lymph circulation.In silico analyses of CD14 molecule reveals significant evolutionary diversity potentially associated with speciation and variable immune response in mammalshttps://peerj.com/preprints/276682019-05-172019-05-17Olanrewaju B MorenikejiBolaji N Thomas
Cluster differentiation gene (CD14) is a family of monocyte differentiating genes that works in conjunction with lipopolysaccharide binding protein (LBP), forming a complex with TLR4 or LY96 to mediate innate immune response to pathogens. In this paper, we used different computational methods to elucidate the evolution of CD14 gene coding region in 14 mammalian species. Our analyses identified leucine rich repeats (LRRs) as the only significant domain across the CD14 protein of the 14 species, presenting with frequencies ranging from 1-4. Importantly, we found signal peptides located at mutational hotspots demonstrating this gene is conserved across these species. Out of the 10 selected variants analyzed in this study, only 6 were predicted to possess significant deleterious effect. Our predicted protein interactome showed a significant varying protein-protein interaction with CD14 protein across the species. This may be important for drug target and therapeutic manipulation for the treatment of many diseases. We conclude that these results contribute to our understanding of the CD14 molecular evolution, which underlays varying species response to complex disease traits.
Cluster differentiation gene (CD14) is a family of monocyte differentiating genes that works in conjunction with lipopolysaccharide binding protein (LBP), forming a complex with TLR4 or LY96 to mediate innate immune response to pathogens. In this paper, we used different computational methods to elucidate the evolution of CD14 gene coding region in 14 mammalian species. Our analyses identified leucine rich repeats (LRRs) as the only significant domain across the CD14 protein of the 14 species, presenting with frequencies ranging from 1-4. Importantly, we found signal peptides located at mutational hotspots demonstrating this gene is conserved across these species. Out of the 10 selected variants analyzed in this study, only 6 were predicted to possess significant deleterious effect. Our predicted protein interactome showed a significant varying protein-protein interaction with CD14 protein across the species. This may be important for drug target and therapeutic manipulation for the treatment of many diseases. We conclude that these results contribute to our understanding of the CD14 molecular evolution, which underlays varying species response to complex disease traits.Sex Matters in Health and Disease: a review of biological sex differences with an emphasis on gliomahttps://peerj.com/preprints/277162019-05-092019-05-09Susan Christine MasseyPaula WhitmireTatum E DoyleJoseph E IppolitoMaciej M MrugalaLeland S HuPeter CanollAlexander R A AndersonMelissa A WilsonSusan M FitzpatrickMargaret M McCarthyJoshua B RubinKristin R Swanson
Humans are sexually dimorphic, with sex being the most persistent difference among humans over the course of our evolutionary history. Beyond the visible sex differences that can be considered true dimorphisms, there are also sex differences at the molecular and cellular scales. The role of these biological sex differences for human health, while being increasingly recognized, have long been underappreciated and underexplored. Frequently, these differences are only recognized in sex–specific diseases, such as genitourinary diseases and cancers. However, given the evidence for sex differences in the most basic aspects of human biology, including metabolism, cellular composition, and immune activity, these differences could have consequences for the etiology and pathophysiology of a majority of diseases. It is thus essential to consider the extent to which these differences may influence the various mechanisms underlying disease processes, response to treatment, and the maintenance of health in order to better improve patient outcomes. Here we review the evidence for a broad array of biological sex differences in humans and discuss how they may relate to observed sex differences in various diseases, with an emphasis on cancer, specifically glioblastoma. We further propose that mathematical approaches can be useful for exploring the extent to which sex differences affect disease outcomes and accounting for those in the development of therapeutic strategies.
Humans are sexually dimorphic, with sex being the most persistent difference among humans over the course of our evolutionary history. Beyond the visible sex differences that can be considered true dimorphisms, there are also sex differences at the molecular and cellular scales. The role of these biological sex differences for human health, while being increasingly recognized, have long been underappreciated and underexplored. Frequently, these differences are only recognized in sex–specific diseases, such as genitourinary diseases and cancers. However, given the evidence for sex differences in the most basic aspects of human biology, including metabolism, cellular composition, and immune activity, these differences could have consequences for the etiology and pathophysiology of a majority of diseases. It is thus essential to consider the extent to which these differences may influence the various mechanisms underlying disease processes, response to treatment, and the maintenance of health in order to better improve patient outcomes. Here we review the evidence for a broad array of biological sex differences in humans and discuss how they may relate to observed sex differences in various diseases, with an emphasis on cancer, specifically glioblastoma. We further propose that mathematical approaches can be useful for exploring the extent to which sex differences affect disease outcomes and accounting for those in the development of therapeutic strategies.Elaborate mechanism for the synthesis of lipopolysaccharide points to its functional importance in Gram-negative bacteriahttps://peerj.com/preprints/276422019-04-082019-04-08Wenfa Ng
Gram-negative bacteria such as Escherichia coli and Salmonella enterica possess two phospholipid bilayer membranes in the cell envelope. Known as the inner and outer membrane, proteins encased in the outer membrane as well as surface moieties displayed by the membrane play important roles in host-cell recognition, cell-cell interactions and triggering of immune response in host. One such molecule that partakes in triggering immune responses in human is lipopolysaccharides that constitute the outer leaflet of the outer membrane of Gram-negative bacteria. Specifically, recent research has added new details and mechanisms for the elaborate choreographed enzymatic reactions that synthesize lipopolysaccharides. In particular, lipopolysaccharides are synthesized in the inner membrane and transported to the outer membrane through a dedicated protein channel formed by proteins of the same lipopolysaccharide synthesis pathway. In short, significant amount of proteins and cellular resources are expended in the synthesis and transport of lipopolysaccharides which suggests important evolutionary significance and functionality of the molecule. Specifically, evolutionary significance of lipopolysaccharide can be gleaned from the organisation of the pathway that mediate its synthesis, where dedicated channels are constructed from proteins to help the unidirectional transfer of the molecule from the inner to outer membrane. Such dedicated channels are not of high occurrence in cells, which suggests critical functional importance of lipopolysaccharides to Gram-negative bacteria. Perhaps, signalling mechanisms responsible for cell-cell interactions are mediated by lipopolysaccharides, or the molecule might play important roles in cellular recognition between different bacterial species in community assemblage such as biofilm. Collectively, mechanistic studies aimed at understanding the formation of the outer membrane of Gram-negative bacteria has opened our eyes to the elaborate mechanism by which lipopolysaccharides on the outer leaflet of the outer membrane are synthesized. Comprising a synthetic machinery and a dedicated protein channel for transporting the synthesized lipopolysaccharides from the inner to outer membrane, a dedicated pathway of proteins mediates the synthesis of this molecule; thereby, pointing to its functional importance to the bacterial cell. While lipopolysaccharides are known to trigger immune responses in humans, its potential broader role in cell-cell communications such as those important for maintaining organisation and community structure in biofilm communities remain unappreciated. Overall, given the significant amount of energy and cellular resources dedicated to its synthesis, lipopolysaccharides should have broader functional roles and might partake in many as-yet unknown signalling and metabolic activities at the cellular and community level.
Gram-negative bacteria such as Escherichia coli and Salmonella enterica possess two phospholipid bilayer membranes in the cell envelope. Known as the inner and outer membrane, proteins encased in the outer membrane as well as surface moieties displayed by the membrane play important roles in host-cell recognition, cell-cell interactions and triggering of immune response in host. One such molecule that partakes in triggering immune responses in human is lipopolysaccharides that constitute the outer leaflet of the outer membrane of Gram-negative bacteria. Specifically, recent research has added new details and mechanisms for the elaborate choreographed enzymatic reactions that synthesize lipopolysaccharides. In particular, lipopolysaccharides are synthesized in the inner membrane and transported to the outer membrane through a dedicated protein channel formed by proteins of the same lipopolysaccharide synthesis pathway. In short, significant amount of proteins and cellular resources are expended in the synthesis and transport of lipopolysaccharides which suggests important evolutionary significance and functionality of the molecule. Specifically, evolutionary significance of lipopolysaccharide can be gleaned from the organisation of the pathway that mediate its synthesis, where dedicated channels are constructed from proteins to help the unidirectional transfer of the molecule from the inner to outer membrane. Such dedicated channels are not of high occurrence in cells, which suggests critical functional importance of lipopolysaccharides to Gram-negative bacteria. Perhaps, signalling mechanisms responsible for cell-cell interactions are mediated by lipopolysaccharides, or the molecule might play important roles in cellular recognition between different bacterial species in community assemblage such as biofilm. Collectively, mechanistic studies aimed at understanding the formation of the outer membrane of Gram-negative bacteria has opened our eyes to the elaborate mechanism by which lipopolysaccharides on the outer leaflet of the outer membrane are synthesized. Comprising a synthetic machinery and a dedicated protein channel for transporting the synthesized lipopolysaccharides from the inner to outer membrane, a dedicated pathway of proteins mediates the synthesis of this molecule; thereby, pointing to its functional importance to the bacterial cell. While lipopolysaccharides are known to trigger immune responses in humans, its potential broader role in cell-cell communications such as those important for maintaining organisation and community structure in biofilm communities remain unappreciated. Overall, given the significant amount of energy and cellular resources dedicated to its synthesis, lipopolysaccharides should have broader functional roles and might partake in many as-yet unknown signalling and metabolic activities at the cellular and community level.Approach to a highly-virulent emerging viral epidemic: A thought experiment and literature reviewhttps://peerj.com/preprints/275182019-02-052019-02-05Mohamed AmgadYousef A FouadMaha AT Elsebaie
What are the immunological facets of a highly successful viral epidemic, and what are likely successful strategies that can be used to counter its spread? Unlike many challenges in biology and public policy, viral epidemics are unique in that they require swift response, and quick application of existing knowledge to infer the underlying biology of a new pathological agent. This essay contextualizes the experience and findings from the viral immunology literature to respond to a hypothetical (yet likely) emerging viral epidemic. It begins with a review of the causes of some defining features of highly virulent viral epidemics, including causes of mortality, viral virulence, and immune evasion and suppression tactics. We provide an overview of lines of investigation to characterize emerging viral epidemics, including a brief survey of clinical and biological assays for immune surveillance and in-depth interrogation of viral biology. Finally, we provide a broad overview of management and vaccine development response strategies.
What are the immunological facets of a highly successful viral epidemic, and what are likely successful strategies that can be used to counter its spread? Unlike many challenges in biology and public policy, viral epidemics are unique in that they require swift response, and quick application of existing knowledge to infer the underlying biology of a new pathological agent. This essay contextualizes the experience and findings from the viral immunology literature to respond to a hypothetical (yet likely) emerging viral epidemic. It begins with a review of the causes of some defining features of highly virulent viral epidemics, including causes of mortality, viral virulence, and immune evasion and suppression tactics. We provide an overview of lines of investigation to characterize emerging viral epidemics, including a brief survey of clinical and biological assays for immune surveillance and in-depth interrogation of viral biology. Finally, we provide a broad overview of management and vaccine development response strategies.