Tara Hurst | University of Oxford (original) (raw)

Papers by Tara Hurst

Pathogens, Mar 2, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Cancers, Dec 4, 2019

Somatic alterations to the genomes of solid tumours, which in some cases represent actionable dri... more Somatic alterations to the genomes of solid tumours, which in some cases represent actionable drivers, provide diagnostic and prognostic insight into these complex diseases. Spatial and longitudinal tracking of somatic genomic alterations (SGAs) in patient tumours has emerged as a new avenue of investigation, not only as a disease monitoring strategy, but also to improve our understanding of heterogeneity and clonal evolution from diagnosis through disease progression. Furthermore, analysis of circulating-free DNA (cfDNA) in the so-called "liquid biopsy" has emerged as a non-invasive method to identify genomic information to inform targeted therapy and may also capture the heterogeneity of the primary and metastatic tumours. Considering the potential of cfDNA analysis as a translational laboratory tool in clinical practice, establishing the extent to which cfDNA represents the SGAs of tumours, particularly actionable driver alterations, becomes a matter of importance, warranting standardisation of methods and practices. Here, we assess the utilisation of cfDNA for molecular profiling of SGAs in tumour tissue across a broad range of solid tumours. Moreover, we examine the underlying factors contributing to discordance of detected SGAs between cfDNA and tumour tissue.

PubMed, Sep 5, 2013

The treatment of HIV-1 infected patients with HAART has resulted in long-term suppression of vira... more The treatment of HIV-1 infected patients with HAART has resulted in long-term suppression of viral replication and reduced progression to AIDS. However, the use of HAART has been associated with adverse effects, including metabolic dysregulation and changes in body fat deposition. This syndrome, known as HIV/HAART-associated lipodystrophy syndrome, is characterized by insulin resistance, dyslipidemia, lipodystrophy, and increased visceral adiposity, which contribute to an increased risk of cardiovascular disease amongst these patients. The thiazolidinediones are a class of agonists for the nuclear receptors, the peroxisome proliferator-activated receptor. Since peroxisome proliferator-activated receptor is critically involved in the regulation of insulin sensitivity and lipid metabolism, a number of clinical trials have analyzed whether thiazolidinediones could ameliorate the signs of HIV/HAART-associated lipodystrophy syndrome. Based on these trials, thiazolidinediones appear to up-regulate peroxisome proliferator-activated receptor-dependent genes such as adiponectin, an effect that could have important physiological benefits in the long-term for HIV/HAART-associated lipodystrophy syndrome patients. Critically, many of the studies were of short duration and thus the beneficial effects of thiazolidinediones might have been missed. In addition, the few studies on the thiazolidinedione pioglitazone showed a beneficial effect on limb fat mass that was not associated with a pro-atherogenic lipid profile. Based on these studies, a large-scale clinical trial of pioglitazone use in HIV/HAART-associated lipodystrophy syndrome patients is warranted.

Journal of Virology, Jun 1, 2009

As nonenveloped viruses, the aquareoviruses and orthoreoviruses are unusual in their ability to i... more As nonenveloped viruses, the aquareoviruses and orthoreoviruses are unusual in their ability to induce cell-cell fusion and syncytium formation. While an extraordinary family of fusion-associated small transmembrane (FAST) proteins is responsible for orthoreovirus syncytiogenesis, the basis for aquareovirus-induced syncytiogenesis is unknown. We now report that the S7 genome segment of an Atlantic salmon reovirus is polycistronic and uses a noncanonical CUG translation start codon to produce a 22-kDa integral membrane protein responsible for syncytiogenesis. The aquareovirus p22 protein represents a fourth distinct member of the FAST family with a unique repertoire and arrangement of structural motifs.

Frontiers in Microbiology, Jul 4, 2019

Hurst et al. IFI16 Binds ssDNA Targets abnormal HK2 replication in somatic tissues. The absence o... more Hurst et al. IFI16 Binds ssDNA Targets abnormal HK2 replication in somatic tissues. The absence of this protein in stem cells and a stem cell line could permit these cells to express HERVs which contribute to stem cell identity. Finally, we also comment on potential studies that could support or refute our hypothesis.

Retrovirology, Feb 6, 2016

Background: While antiretroviral therapies have improved life expectancy and reduced viral loads ... more Background: While antiretroviral therapies have improved life expectancy and reduced viral loads in HIV-1-positive individuals, the cessation of treatment results in a rebound of viral replication. This suggests that a reservoir of latently-infected cells remains within these patients, the identity of which is ill-defined and therefore difficult to target therapeutically. Current strategies are aimed at using drugs such as histone deacetylase (HDAC) inhibitors to induce the expression of latent HIV-1 proviruses in order to activate and ultimately eradicate this reservoir of infected cells. One concern with the use of HDAC inhibitors is that they could up-regulate human endogenous retroviruses (HERVs), as well as HIV-1, with potentially pathophysiological consequences. Results: In this study, we analysed the transcription of HERV genes in HIV-1 latency T cell (J-LAT 8.4) and monocyte (U1) models following treatment with the HDAC inhibitors, vorinostat, panobinostat and romidepsin. We examined the expression of HERV-K (HML-2) env and pol, as well as the co-opted genes HERV-W env (syncytin-1), HERV-FRD env (syncytin-2), in these cell lines. Finally, we investigated HERV expression in primary human T cells. Conclusions: We show that HDAC inhibitors did not substantially increase the transcription of the analysed HERV env or pol genes, suggesting that histone acetylation is not crucial for controlling HERV expression in these experimental models and in ex vivo primary human T cells. Importantly, this indicates that unwanted HERV expression does not appear to be a barrier to the use of HDAC inhibitors in HIV-1 cure strategies.

THESIS 8670%%%%Large DNA viruses, like Vaccinia virus (VACV), encode numerous proteins that are n... more THESIS 8670%%%%Large DNA viruses, like Vaccinia virus (VACV), encode numerous proteins that are not essential for viral replication but which modulate the antiviral immune response. A number of VACV immunomodulatory proteins have been found to target different components of the innate immune response, including interleukin-1 receptor/ Toll-like receptor (IL-1R/TLR) signalling pathways. The VACV protein A52 has previously been shown to interact with two members of the IL-1R/TLR signalling pathways, TRAF6 and IRAK2. Further, A52 is a potent inhibitor of IL-IR/TLR-induced NF-kB activation, likely by inhibiting the function of IRAK2. Interestingly, A52 was also found to activate p38 MAP kinase (MARK), enhancing TLR-dependent IL-10 induction. The interaction between A52 and TRAF6 was found to be crucial for A52-induced MARK activation.

Future Virology, Mar 1, 2008

In recent years there has been an avalanche of new data revealing how the innate immune system, u... more In recent years there has been an avalanche of new data revealing how the innate immune system, using pattern recognition receptors, initially senses viruses. This leads to signaling pathways resulting in transcription factor activation, and subsequent induction of cytokines and interferons. Here we show how studying the immune evasion strategies of vaccinia virus, and elucidating the underlying molecular mechanisms of these strategies, has provided some important lessons as to how these pathways operate and how they are subverted by viruses.

Viruses, May 31, 2017

Transposable elements, including endogenous retroviruses (ERVs), comprise almost 45% of the human... more Transposable elements, including endogenous retroviruses (ERVs), comprise almost 45% of the human genome. This could represent a significant pathogenic burden but it is becoming more evident that many of these elements have a positive contribution to make to normal human physiology. In particular, the contributions of human ERVs (HERVs) to gene regulation and the expression of noncoding RNAs has been revealed with the help of new and emerging genomic technologies. HERVs have the common provirus structure of coding open reading frames (ORFs) flanked by two long-terminal repeats (LTRs). However, over the course of evolution and as a consequence of host defence mechanisms, most of the sequences contain INDELs, mutations or have been reduced to single LTRs by recombination. These INDELs and mutations reduce HERV activity. However, there is a trade-off for the host cells in that HERVs can provide beneficial sources of genetic variation but with this benefit comes the risk of pathogenic activity and spread within the genome. For example, the LTRs are of critical importance as they contain promoter sequences and can regulate not only HERV expression but that of human genes. This is true even when the LTRs are located in intergenic regions or are in antisense orientation to the rest of the gene. Uncontrolled, this promoter activity could disrupt normal gene expression or transcript processing (e.g., splicing). Thus, control of HERVs and particularly their LTRs is essential for the cell to manage these elements and this control is achieved at multiple levels, including epigenetic regulations that permit HERV expression in the germline but silence it in most somatic tissues. We will discuss some of the common epigenetic mechanisms and how they affect HERV expression, providing detailed discussions of HERVs in stem cell, placenta and cancer biology.

Frontiers in Oncology, 2022

Frontiers Research Topics, 2019

This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics... more This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac

Vaccines, 2020

The stalk domain of the hemagglutinin has been identified as a target for induction of protective... more The stalk domain of the hemagglutinin has been identified as a target for induction of protective antibody responses due to its high degree of conservation among numerous influenza subtypes and strains. However, current assays to measure stalk-based immunity are not standardized. Hence, harmonization of assay readouts would help to compare experiments conducted in different laboratories and increase confidence in results. Here, serum samples from healthy individuals (n = 110) were screened using a chimeric cH6/1 hemagglutinin enzyme-linked immunosorbent assay (ELISA) that measures stalk-reactive antibodies. We identified samples with moderate to high IgG anti-stalk antibody levels. Likewise, screening of the samples using the mini-hemagglutinin (HA) headless construct #4900 and analysis of the correlation between the two assays confirmed the presence and specificity of anti-stalk antibodies. Additionally, samples were characterized by a cH6/1N5 virus-based neutralization assay, an a...

Pathogens, 2022

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavi... more The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), poses several challenges to clinicians, due to its unpredictable clinical course. The identification of laboratory biomarkers, specific cellular, and molecular mediators of immune response could contribute to the prognosis and management of COVID-19 patients. Of utmost importance is also the detection of differentially expressed genes, which can serve as transcriptomic signatures, providing information valuable to stratify patients into groups, based on the severity of the disease. The role of biomarkers such as IL-6, procalcitonin, neutrophil–lymphocyte ratio, white blood cell counts, etc. has already been highlighted in recently published studies; however, there is a notable amount of new evidence that has not been summarized yet, especially regarding transcriptomic signatures. Hence, in this review, we assess the latest cellular and molecular data and determine the...

Additional file 1. Sequences of primers and Molecular Beacon probes used in qPCRs. All HERV probe... more Additional file 1. Sequences of primers and Molecular Beacon probes used in qPCRs. All HERV probes were labelled with 6-Fam (5') and BHQ1 (3'), while GAPDH probe was labelled with HEX (5') and BHQ1 (3').

THESIS 8670%%%%Large DNA viruses, like Vaccinia virus (VACV), encode numerous proteins that are n... more THESIS 8670%%%%Large DNA viruses, like Vaccinia virus (VACV), encode numerous proteins that are not essential for viral replication but which modulate the antiviral immune response. A number of VACV immunomodulatory proteins have been found to target different components of the innate immune response, including interleukin-1 receptor/ Toll-like receptor (IL-1R/TLR) signalling pathways. The VACV protein A52 has previously been shown to interact with two members of the IL-1R/TLR signalling pathways, TRAF6 and IRAK2. Further, A52 is a potent inhibitor of IL-IR/TLR-induced NF-kB activation, likely by inhibiting the function of IRAK2. Interestingly, A52 was also found to activate p38 MAP kinase (MARK), enhancing TLR-dependent IL-10 induction. The interaction between A52 and TRAF6 was found to be crucial for A52-induced MARK activation.

Frontiers in immunology, 2018

The greatest obstacle to a cure for HIV is the provirus that integrates into the genome of the in... more The greatest obstacle to a cure for HIV is the provirus that integrates into the genome of the infected cell and persists despite antiretroviral therapy. A "shock and kill" approach has been proposed as a strategy for an HIV cure whereby drugs and compounds referred to as latency-reversing agents (LRAs) are used to "shock" the silent provirus into active replication to permit "killing" by virus-induced pathology or immune recognition. The LRA most utilized to date in clinical trials has been the histone deacetylase (HDAC) inhibitor-vorinostat. Potentially, pathological off-target effects of vorinostat may result from the activation of human endogenous retroviruses (HERVs), which share common ancestry with exogenous retroviruses including HIV. To explore the effects of HDAC inhibition on HERV transcription, an unbiased pharmacogenomics approach (total RNA-Seq) was used to evaluate HERV expression following the exposure of primary CD4 T cells to a high do...

Viruses, May 31, 2017

Transposable elements, including endogenous retroviruses (ERVs), comprise almost 45% of the human... more Transposable elements, including endogenous retroviruses (ERVs), comprise almost 45% of the human genome. This could represent a significant pathogenic burden but it is becoming more evident that many of these elements have a positive contribution to make to normal human physiology. In particular, the contributions of human ERVs (HERVs) to gene regulation and the expression of noncoding RNAs has been revealed with the help of new and emerging genomic technologies. HERVs have the common provirus structure of coding open reading frames (ORFs) flanked by two long-terminal repeats (LTRs). However, over the course of evolution and as a consequence of host defence mechanisms, most of the sequences contain INDELs, mutations or have been reduced to single LTRs by recombination. These INDELs and mutations reduce HERV activity. However, there is a trade-off for the host cells in that HERVs can provide beneficial sources of genetic variation but with this benefit comes the risk of pathogenic a...

Pathogens, Mar 2, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Cancers, Dec 4, 2019

Somatic alterations to the genomes of solid tumours, which in some cases represent actionable dri... more Somatic alterations to the genomes of solid tumours, which in some cases represent actionable drivers, provide diagnostic and prognostic insight into these complex diseases. Spatial and longitudinal tracking of somatic genomic alterations (SGAs) in patient tumours has emerged as a new avenue of investigation, not only as a disease monitoring strategy, but also to improve our understanding of heterogeneity and clonal evolution from diagnosis through disease progression. Furthermore, analysis of circulating-free DNA (cfDNA) in the so-called "liquid biopsy" has emerged as a non-invasive method to identify genomic information to inform targeted therapy and may also capture the heterogeneity of the primary and metastatic tumours. Considering the potential of cfDNA analysis as a translational laboratory tool in clinical practice, establishing the extent to which cfDNA represents the SGAs of tumours, particularly actionable driver alterations, becomes a matter of importance, warranting standardisation of methods and practices. Here, we assess the utilisation of cfDNA for molecular profiling of SGAs in tumour tissue across a broad range of solid tumours. Moreover, we examine the underlying factors contributing to discordance of detected SGAs between cfDNA and tumour tissue.

PubMed, Sep 5, 2013

The treatment of HIV-1 infected patients with HAART has resulted in long-term suppression of vira... more The treatment of HIV-1 infected patients with HAART has resulted in long-term suppression of viral replication and reduced progression to AIDS. However, the use of HAART has been associated with adverse effects, including metabolic dysregulation and changes in body fat deposition. This syndrome, known as HIV/HAART-associated lipodystrophy syndrome, is characterized by insulin resistance, dyslipidemia, lipodystrophy, and increased visceral adiposity, which contribute to an increased risk of cardiovascular disease amongst these patients. The thiazolidinediones are a class of agonists for the nuclear receptors, the peroxisome proliferator-activated receptor. Since peroxisome proliferator-activated receptor is critically involved in the regulation of insulin sensitivity and lipid metabolism, a number of clinical trials have analyzed whether thiazolidinediones could ameliorate the signs of HIV/HAART-associated lipodystrophy syndrome. Based on these trials, thiazolidinediones appear to up-regulate peroxisome proliferator-activated receptor-dependent genes such as adiponectin, an effect that could have important physiological benefits in the long-term for HIV/HAART-associated lipodystrophy syndrome patients. Critically, many of the studies were of short duration and thus the beneficial effects of thiazolidinediones might have been missed. In addition, the few studies on the thiazolidinedione pioglitazone showed a beneficial effect on limb fat mass that was not associated with a pro-atherogenic lipid profile. Based on these studies, a large-scale clinical trial of pioglitazone use in HIV/HAART-associated lipodystrophy syndrome patients is warranted.

Journal of Virology, Jun 1, 2009

As nonenveloped viruses, the aquareoviruses and orthoreoviruses are unusual in their ability to i... more As nonenveloped viruses, the aquareoviruses and orthoreoviruses are unusual in their ability to induce cell-cell fusion and syncytium formation. While an extraordinary family of fusion-associated small transmembrane (FAST) proteins is responsible for orthoreovirus syncytiogenesis, the basis for aquareovirus-induced syncytiogenesis is unknown. We now report that the S7 genome segment of an Atlantic salmon reovirus is polycistronic and uses a noncanonical CUG translation start codon to produce a 22-kDa integral membrane protein responsible for syncytiogenesis. The aquareovirus p22 protein represents a fourth distinct member of the FAST family with a unique repertoire and arrangement of structural motifs.

Frontiers in Microbiology, Jul 4, 2019

Hurst et al. IFI16 Binds ssDNA Targets abnormal HK2 replication in somatic tissues. The absence o... more Hurst et al. IFI16 Binds ssDNA Targets abnormal HK2 replication in somatic tissues. The absence of this protein in stem cells and a stem cell line could permit these cells to express HERVs which contribute to stem cell identity. Finally, we also comment on potential studies that could support or refute our hypothesis.

Retrovirology, Feb 6, 2016

Background: While antiretroviral therapies have improved life expectancy and reduced viral loads ... more Background: While antiretroviral therapies have improved life expectancy and reduced viral loads in HIV-1-positive individuals, the cessation of treatment results in a rebound of viral replication. This suggests that a reservoir of latently-infected cells remains within these patients, the identity of which is ill-defined and therefore difficult to target therapeutically. Current strategies are aimed at using drugs such as histone deacetylase (HDAC) inhibitors to induce the expression of latent HIV-1 proviruses in order to activate and ultimately eradicate this reservoir of infected cells. One concern with the use of HDAC inhibitors is that they could up-regulate human endogenous retroviruses (HERVs), as well as HIV-1, with potentially pathophysiological consequences. Results: In this study, we analysed the transcription of HERV genes in HIV-1 latency T cell (J-LAT 8.4) and monocyte (U1) models following treatment with the HDAC inhibitors, vorinostat, panobinostat and romidepsin. We examined the expression of HERV-K (HML-2) env and pol, as well as the co-opted genes HERV-W env (syncytin-1), HERV-FRD env (syncytin-2), in these cell lines. Finally, we investigated HERV expression in primary human T cells. Conclusions: We show that HDAC inhibitors did not substantially increase the transcription of the analysed HERV env or pol genes, suggesting that histone acetylation is not crucial for controlling HERV expression in these experimental models and in ex vivo primary human T cells. Importantly, this indicates that unwanted HERV expression does not appear to be a barrier to the use of HDAC inhibitors in HIV-1 cure strategies.

THESIS 8670%%%%Large DNA viruses, like Vaccinia virus (VACV), encode numerous proteins that are n... more THESIS 8670%%%%Large DNA viruses, like Vaccinia virus (VACV), encode numerous proteins that are not essential for viral replication but which modulate the antiviral immune response. A number of VACV immunomodulatory proteins have been found to target different components of the innate immune response, including interleukin-1 receptor/ Toll-like receptor (IL-1R/TLR) signalling pathways. The VACV protein A52 has previously been shown to interact with two members of the IL-1R/TLR signalling pathways, TRAF6 and IRAK2. Further, A52 is a potent inhibitor of IL-IR/TLR-induced NF-kB activation, likely by inhibiting the function of IRAK2. Interestingly, A52 was also found to activate p38 MAP kinase (MARK), enhancing TLR-dependent IL-10 induction. The interaction between A52 and TRAF6 was found to be crucial for A52-induced MARK activation.

Future Virology, Mar 1, 2008

In recent years there has been an avalanche of new data revealing how the innate immune system, u... more In recent years there has been an avalanche of new data revealing how the innate immune system, using pattern recognition receptors, initially senses viruses. This leads to signaling pathways resulting in transcription factor activation, and subsequent induction of cytokines and interferons. Here we show how studying the immune evasion strategies of vaccinia virus, and elucidating the underlying molecular mechanisms of these strategies, has provided some important lessons as to how these pathways operate and how they are subverted by viruses.

Viruses, May 31, 2017

Transposable elements, including endogenous retroviruses (ERVs), comprise almost 45% of the human... more Transposable elements, including endogenous retroviruses (ERVs), comprise almost 45% of the human genome. This could represent a significant pathogenic burden but it is becoming more evident that many of these elements have a positive contribution to make to normal human physiology. In particular, the contributions of human ERVs (HERVs) to gene regulation and the expression of noncoding RNAs has been revealed with the help of new and emerging genomic technologies. HERVs have the common provirus structure of coding open reading frames (ORFs) flanked by two long-terminal repeats (LTRs). However, over the course of evolution and as a consequence of host defence mechanisms, most of the sequences contain INDELs, mutations or have been reduced to single LTRs by recombination. These INDELs and mutations reduce HERV activity. However, there is a trade-off for the host cells in that HERVs can provide beneficial sources of genetic variation but with this benefit comes the risk of pathogenic activity and spread within the genome. For example, the LTRs are of critical importance as they contain promoter sequences and can regulate not only HERV expression but that of human genes. This is true even when the LTRs are located in intergenic regions or are in antisense orientation to the rest of the gene. Uncontrolled, this promoter activity could disrupt normal gene expression or transcript processing (e.g., splicing). Thus, control of HERVs and particularly their LTRs is essential for the cell to manage these elements and this control is achieved at multiple levels, including epigenetic regulations that permit HERV expression in the germline but silence it in most somatic tissues. We will discuss some of the common epigenetic mechanisms and how they affect HERV expression, providing detailed discussions of HERVs in stem cell, placenta and cancer biology.

Frontiers in Oncology, 2022

Frontiers Research Topics, 2019

This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics... more This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac

Vaccines, 2020

The stalk domain of the hemagglutinin has been identified as a target for induction of protective... more The stalk domain of the hemagglutinin has been identified as a target for induction of protective antibody responses due to its high degree of conservation among numerous influenza subtypes and strains. However, current assays to measure stalk-based immunity are not standardized. Hence, harmonization of assay readouts would help to compare experiments conducted in different laboratories and increase confidence in results. Here, serum samples from healthy individuals (n = 110) were screened using a chimeric cH6/1 hemagglutinin enzyme-linked immunosorbent assay (ELISA) that measures stalk-reactive antibodies. We identified samples with moderate to high IgG anti-stalk antibody levels. Likewise, screening of the samples using the mini-hemagglutinin (HA) headless construct #4900 and analysis of the correlation between the two assays confirmed the presence and specificity of anti-stalk antibodies. Additionally, samples were characterized by a cH6/1N5 virus-based neutralization assay, an a...

Pathogens, 2022

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavi... more The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), poses several challenges to clinicians, due to its unpredictable clinical course. The identification of laboratory biomarkers, specific cellular, and molecular mediators of immune response could contribute to the prognosis and management of COVID-19 patients. Of utmost importance is also the detection of differentially expressed genes, which can serve as transcriptomic signatures, providing information valuable to stratify patients into groups, based on the severity of the disease. The role of biomarkers such as IL-6, procalcitonin, neutrophil–lymphocyte ratio, white blood cell counts, etc. has already been highlighted in recently published studies; however, there is a notable amount of new evidence that has not been summarized yet, especially regarding transcriptomic signatures. Hence, in this review, we assess the latest cellular and molecular data and determine the...

Additional file 1. Sequences of primers and Molecular Beacon probes used in qPCRs. All HERV probe... more Additional file 1. Sequences of primers and Molecular Beacon probes used in qPCRs. All HERV probes were labelled with 6-Fam (5') and BHQ1 (3'), while GAPDH probe was labelled with HEX (5') and BHQ1 (3').

THESIS 8670%%%%Large DNA viruses, like Vaccinia virus (VACV), encode numerous proteins that are n... more THESIS 8670%%%%Large DNA viruses, like Vaccinia virus (VACV), encode numerous proteins that are not essential for viral replication but which modulate the antiviral immune response. A number of VACV immunomodulatory proteins have been found to target different components of the innate immune response, including interleukin-1 receptor/ Toll-like receptor (IL-1R/TLR) signalling pathways. The VACV protein A52 has previously been shown to interact with two members of the IL-1R/TLR signalling pathways, TRAF6 and IRAK2. Further, A52 is a potent inhibitor of IL-IR/TLR-induced NF-kB activation, likely by inhibiting the function of IRAK2. Interestingly, A52 was also found to activate p38 MAP kinase (MARK), enhancing TLR-dependent IL-10 induction. The interaction between A52 and TRAF6 was found to be crucial for A52-induced MARK activation.

Frontiers in immunology, 2018

The greatest obstacle to a cure for HIV is the provirus that integrates into the genome of the in... more The greatest obstacle to a cure for HIV is the provirus that integrates into the genome of the infected cell and persists despite antiretroviral therapy. A "shock and kill" approach has been proposed as a strategy for an HIV cure whereby drugs and compounds referred to as latency-reversing agents (LRAs) are used to "shock" the silent provirus into active replication to permit "killing" by virus-induced pathology or immune recognition. The LRA most utilized to date in clinical trials has been the histone deacetylase (HDAC) inhibitor-vorinostat. Potentially, pathological off-target effects of vorinostat may result from the activation of human endogenous retroviruses (HERVs), which share common ancestry with exogenous retroviruses including HIV. To explore the effects of HDAC inhibition on HERV transcription, an unbiased pharmacogenomics approach (total RNA-Seq) was used to evaluate HERV expression following the exposure of primary CD4 T cells to a high do...

Viruses, May 31, 2017

Transposable elements, including endogenous retroviruses (ERVs), comprise almost 45% of the human... more Transposable elements, including endogenous retroviruses (ERVs), comprise almost 45% of the human genome. This could represent a significant pathogenic burden but it is becoming more evident that many of these elements have a positive contribution to make to normal human physiology. In particular, the contributions of human ERVs (HERVs) to gene regulation and the expression of noncoding RNAs has been revealed with the help of new and emerging genomic technologies. HERVs have the common provirus structure of coding open reading frames (ORFs) flanked by two long-terminal repeats (LTRs). However, over the course of evolution and as a consequence of host defence mechanisms, most of the sequences contain INDELs, mutations or have been reduced to single LTRs by recombination. These INDELs and mutations reduce HERV activity. However, there is a trade-off for the host cells in that HERVs can provide beneficial sources of genetic variation but with this benefit comes the risk of pathogenic a...