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Research paper thumbnail of HIV-1 Tat amino acid residues that influence Tat-TAR binding affinity: a scoping review

BMC Infectious Diseases

HIV-1 remains a global health concern and to date, nearly 38 million people are living with HIV. ... more HIV-1 remains a global health concern and to date, nearly 38 million people are living with HIV. The complexity of HIV-1 pathogenesis and its subsequent prevalence is influenced by several factors including the HIV-1 subtype. HIV-1 subtype variation extends to sequence variation in the amino acids of the HIV-1 viral proteins. Of particular interest is the transactivation of transcription (Tat) protein due to its key function in viral transcription. The Tat protein predominantly functions by binding to the transactivation response (TAR) RNA element to activate HIV-1 transcriptional elongation. Subtype-specific Tat protein sequence variation influences Tat-TAR binding affinity. Despite several studies investigating Tat-TAR binding, it is not clear which regions of the Tat protein and/or individual Tat amino acid residues may contribute to TAR binding affinity. We, therefore, conducted a scoping review on studies investigating Tat-TAR binding. We aimed to synthesize the published data ...

Research paper thumbnail of An investigation of a neuro-inflammatory profile of HIV-associated neurocognitive disorders

This manuscript served as the second chapter presenting empirical data and was a follow-up of cha... more This manuscript served as the second chapter presenting empirical data and was a follow-up of chapter 3. Several immune markers were associated with HIVassociated neurocognitive impairment (Chapter 3). The current chapter determined the association of blood immune markers with cortical thickness and surface area measured by MRI. I conducted the laboratory ELISA experiments myself. This study was performed in samples that were obtained from cohorts of Prof. John Joska and Dr. Jonathan Ipser. Together with Ms. Alyssa Amod and Dr. Jonathan Ipser, I conducted the quality control of all MRI data and I generated the output data myself.

Research paper thumbnail of The glycine N-acyltransferases, GLYAT and GLYATL1, contribute to the detoxification of isovaleryl-CoA - an in-silico and in vitro validation

Computational and Structural Biotechnology Journal

Research paper thumbnail of The influence of viral protein R amino acid substitutions on clinical outcomes in people living with HIV : A systematic review

European Journal of Clinical Investigation

Research paper thumbnail of An investigation of the HIV Tat C31S and R57S mutation on peripheral immune marker levels in South African participants: A pilot study

Journal of Medical Virology, 2022

Research paper thumbnail of Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders

Frontiers in Microbiology, 2022

HIV-1 is responsible for a spectrum of neurocognitive deficits defined as HIV-associated neurocog... more HIV-1 is responsible for a spectrum of neurocognitive deficits defined as HIV-associated neurocognitive disorders (HAND). The HIV transactivator of transcription (Tat) protein plays a key role in the neuropathophysiology of HAND. The Tat protein functions by transactivation of viral genes through its interaction with the transactivation response (TAR) RNA element. Subtype-specific Tat protein signatures including C31S, R57S and Q63E present in Tat subtype C has previously been linked to a lowered neuropathophysiology compared to Tat subtype B. In this study, we attempted to understand the molecular mechanism by which Tat subtype-specific variation, particularly, C31S, R57S, and Q63E influence the Tat-TAR interaction. We performed molecular modeling to generate accurate three-dimensional protein structures of the HIV-1 Tat subtypes C and B using the Swiss model webserver. Thereafter, we performed a molecular docking of the TAR RNA element to each of the Tat subtypes B and C protein s...

Research paper thumbnail of Immune Dysregulation Is Associated with Neurodevelopment and Neurocognitive Performance in HIV Pediatric Populations—A Scoping Review

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

Research paper thumbnail of Cerebrospinal fluid immune markers and HIV-associated neurocognitive impairments: A systematic review

Journal of Neuroimmunology

HIV-1 is responsible for the development of a spectrum of cognitive impairments known as HIV-asso... more HIV-1 is responsible for the development of a spectrum of cognitive impairments known as HIV-associated neurocognitive disorder (HAND). In the era of antiretroviral therapy (ART), HAND remains prevalent in people living with HIV (PLWH), despite low or undetectable viral loads. Persistent neuroinflammation likely plays an important role in the contributing biological mechanisms. Multiple cerebrospinal fluid (CSF) immune markers have been studied but it is unclear which markers most consistently correlate with neurocognitive impairment. We therefore conducted a systematic review of studies of the association of CSF immune markers with neurocognitive performance in ART-experienced PLWH. We aimed to synthesize the published data to determine consistent findings and to indicate the most noteworthy CSF markers of HAND. Twenty-nine studies were included, with 20 cross-sectional studies and 9 longitudinal studies. From the group of markers most often assayed, specific monocyte activation (higher levels of Neopterin, sCD163, sCD14) and neuroinflammatory markers (higher levels of IFN-γ, IL-1α, IL-7, IL-8, sTNFR-II and lower levels of IL-6) showed a consistent direction in association with HIV-associated neurocognitive impairment. Furthermore, significant differences exist in CSF immune markers between HIV-positive people with and without neurocognitive impairment, regardless of viral load and nadir/current CD4+ count. These markers may be useful in furthering our understanding of the neuropathology, diagnosis and prognosis of HAND. Studies using prospective designs (i.e. pre- and post-interventions), "multi-modal" methods (e.g. imaging, inflammation and neurocognitive evaluations) and utilizing a combination of the markers most commonly associated with HAND may help delineate the mechanisms of HAND.

Research paper thumbnail of The association of peripheral immune markers with brain cortical thickness and surface area in South African people living with HIV

Research paper thumbnail of Insult to Injury-Potential Contribution of Coronavirus Disease-19 to Neuroinflammation and the Development of HIV-Associated Neurocognitive Disorders

AIDS Research and Human Retroviruses

Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 is responsible for a new coronavirus... more Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 is responsible for a new coronavirus disease known as coronavirus disease-19 (COVID-19). SARS-CoV-2 reports neurotropic properties and may have neurological implications, and this creates another health burden for people living with HIV. As yet, the impact of COVID-19 on (neuro)inflammation and the development of HIV-associated neurocognitive disorders (HAND) is not fully known. Here, we reviewed preliminary evidence that provides clues that COVID-19 may exacerbate inflammatory mechanisms related to the development of HAND.

Research paper thumbnail of Proteomics and metabolomics of HIV‐associated neurocognitive disorders: A systematic review

Journal of Neurochemistry

Research paper thumbnail of Peripheral immune dysregulation in the ART era of HIV-associated neurocognitive impairments: A systematic review

Research paper thumbnail of The Association of Immune Markers with Cognitive Performance in South African HIV-Positive Patients

Journal of Neuroimmune Pharmacology

Research paper thumbnail of Molecular Validation of Putative Antimicrobial Peptides for Improved Human Immunodeficency Virus Diagnostics via HIV Protein P24

Open Forum Infectious Diseases, 2015

Research paper thumbnail of Molecular Validation of Putative Antimicrobial Peptides for Improved Human Immunodeficiency Virus Diagnostics via HIV Protein p24

Journal of AIDS & Clinical Research, 2016

Research paper thumbnail of Signatures of HIV-1 subtype B and C Tat proteins and their effects in the neuropathogenesis of HIV-associated neurocognitive impairments

Research paper thumbnail of HIV-1 Tat amino acid residues that influence Tat-TAR binding affinity: a scoping review

BMC Infectious Diseases

HIV-1 remains a global health concern and to date, nearly 38 million people are living with HIV. ... more HIV-1 remains a global health concern and to date, nearly 38 million people are living with HIV. The complexity of HIV-1 pathogenesis and its subsequent prevalence is influenced by several factors including the HIV-1 subtype. HIV-1 subtype variation extends to sequence variation in the amino acids of the HIV-1 viral proteins. Of particular interest is the transactivation of transcription (Tat) protein due to its key function in viral transcription. The Tat protein predominantly functions by binding to the transactivation response (TAR) RNA element to activate HIV-1 transcriptional elongation. Subtype-specific Tat protein sequence variation influences Tat-TAR binding affinity. Despite several studies investigating Tat-TAR binding, it is not clear which regions of the Tat protein and/or individual Tat amino acid residues may contribute to TAR binding affinity. We, therefore, conducted a scoping review on studies investigating Tat-TAR binding. We aimed to synthesize the published data ...

Research paper thumbnail of An investigation of a neuro-inflammatory profile of HIV-associated neurocognitive disorders

This manuscript served as the second chapter presenting empirical data and was a follow-up of cha... more This manuscript served as the second chapter presenting empirical data and was a follow-up of chapter 3. Several immune markers were associated with HIVassociated neurocognitive impairment (Chapter 3). The current chapter determined the association of blood immune markers with cortical thickness and surface area measured by MRI. I conducted the laboratory ELISA experiments myself. This study was performed in samples that were obtained from cohorts of Prof. John Joska and Dr. Jonathan Ipser. Together with Ms. Alyssa Amod and Dr. Jonathan Ipser, I conducted the quality control of all MRI data and I generated the output data myself.

Research paper thumbnail of The glycine N-acyltransferases, GLYAT and GLYATL1, contribute to the detoxification of isovaleryl-CoA - an in-silico and in vitro validation

Computational and Structural Biotechnology Journal

Research paper thumbnail of The influence of viral protein R amino acid substitutions on clinical outcomes in people living with HIV : A systematic review

European Journal of Clinical Investigation

Research paper thumbnail of An investigation of the HIV Tat C31S and R57S mutation on peripheral immune marker levels in South African participants: A pilot study

Journal of Medical Virology, 2022

Research paper thumbnail of Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders

Frontiers in Microbiology, 2022

HIV-1 is responsible for a spectrum of neurocognitive deficits defined as HIV-associated neurocog... more HIV-1 is responsible for a spectrum of neurocognitive deficits defined as HIV-associated neurocognitive disorders (HAND). The HIV transactivator of transcription (Tat) protein plays a key role in the neuropathophysiology of HAND. The Tat protein functions by transactivation of viral genes through its interaction with the transactivation response (TAR) RNA element. Subtype-specific Tat protein signatures including C31S, R57S and Q63E present in Tat subtype C has previously been linked to a lowered neuropathophysiology compared to Tat subtype B. In this study, we attempted to understand the molecular mechanism by which Tat subtype-specific variation, particularly, C31S, R57S, and Q63E influence the Tat-TAR interaction. We performed molecular modeling to generate accurate three-dimensional protein structures of the HIV-1 Tat subtypes C and B using the Swiss model webserver. Thereafter, we performed a molecular docking of the TAR RNA element to each of the Tat subtypes B and C protein s...

Research paper thumbnail of Immune Dysregulation Is Associated with Neurodevelopment and Neurocognitive Performance in HIV Pediatric Populations—A Scoping Review

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

Research paper thumbnail of Cerebrospinal fluid immune markers and HIV-associated neurocognitive impairments: A systematic review

Journal of Neuroimmunology

HIV-1 is responsible for the development of a spectrum of cognitive impairments known as HIV-asso... more HIV-1 is responsible for the development of a spectrum of cognitive impairments known as HIV-associated neurocognitive disorder (HAND). In the era of antiretroviral therapy (ART), HAND remains prevalent in people living with HIV (PLWH), despite low or undetectable viral loads. Persistent neuroinflammation likely plays an important role in the contributing biological mechanisms. Multiple cerebrospinal fluid (CSF) immune markers have been studied but it is unclear which markers most consistently correlate with neurocognitive impairment. We therefore conducted a systematic review of studies of the association of CSF immune markers with neurocognitive performance in ART-experienced PLWH. We aimed to synthesize the published data to determine consistent findings and to indicate the most noteworthy CSF markers of HAND. Twenty-nine studies were included, with 20 cross-sectional studies and 9 longitudinal studies. From the group of markers most often assayed, specific monocyte activation (higher levels of Neopterin, sCD163, sCD14) and neuroinflammatory markers (higher levels of IFN-γ, IL-1α, IL-7, IL-8, sTNFR-II and lower levels of IL-6) showed a consistent direction in association with HIV-associated neurocognitive impairment. Furthermore, significant differences exist in CSF immune markers between HIV-positive people with and without neurocognitive impairment, regardless of viral load and nadir/current CD4+ count. These markers may be useful in furthering our understanding of the neuropathology, diagnosis and prognosis of HAND. Studies using prospective designs (i.e. pre- and post-interventions), "multi-modal" methods (e.g. imaging, inflammation and neurocognitive evaluations) and utilizing a combination of the markers most commonly associated with HAND may help delineate the mechanisms of HAND.

Research paper thumbnail of The association of peripheral immune markers with brain cortical thickness and surface area in South African people living with HIV

Research paper thumbnail of Insult to Injury-Potential Contribution of Coronavirus Disease-19 to Neuroinflammation and the Development of HIV-Associated Neurocognitive Disorders

AIDS Research and Human Retroviruses

Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 is responsible for a new coronavirus... more Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 is responsible for a new coronavirus disease known as coronavirus disease-19 (COVID-19). SARS-CoV-2 reports neurotropic properties and may have neurological implications, and this creates another health burden for people living with HIV. As yet, the impact of COVID-19 on (neuro)inflammation and the development of HIV-associated neurocognitive disorders (HAND) is not fully known. Here, we reviewed preliminary evidence that provides clues that COVID-19 may exacerbate inflammatory mechanisms related to the development of HAND.

Research paper thumbnail of Proteomics and metabolomics of HIV‐associated neurocognitive disorders: A systematic review

Journal of Neurochemistry

Research paper thumbnail of Peripheral immune dysregulation in the ART era of HIV-associated neurocognitive impairments: A systematic review

Research paper thumbnail of The Association of Immune Markers with Cognitive Performance in South African HIV-Positive Patients

Journal of Neuroimmune Pharmacology

Research paper thumbnail of Molecular Validation of Putative Antimicrobial Peptides for Improved Human Immunodeficency Virus Diagnostics via HIV Protein P24

Open Forum Infectious Diseases, 2015

Research paper thumbnail of Molecular Validation of Putative Antimicrobial Peptides for Improved Human Immunodeficiency Virus Diagnostics via HIV Protein p24

Journal of AIDS & Clinical Research, 2016

Research paper thumbnail of Signatures of HIV-1 subtype B and C Tat proteins and their effects in the neuropathogenesis of HIV-associated neurocognitive impairments