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Article ; Online: The crossroads: divergent roles of virus-specific CD4

van Bockel, David / Kelleher, Anthony

2023 Volume 101, Issue 6, Page(s) 525–534

Abstract: Despite the widespread availability of effective prophylactic vaccines to prevent human papillomavirus (HPV) infection, HPV remains a major health burden. For health care systems in countries with the capacity for vaccine roll out, incomplete strategies ... ...

Abstract	Despite the widespread availability of effective prophylactic vaccines to prevent human papillomavirus (HPV) infection, HPV remains a major health burden. For health care systems in countries with the capacity for vaccine roll out, incomplete strategies result in citizens with naturally occurring infection, who are at an a posteriori risk of HPV-driven disease. Genital HPV infection is the most common sexually transmitted virus globally. Those classified as high-risk HPV strains are more likely to generate persistent disease. Within this group, HPV16 and 18 are the most prevalent and likely to induce persistent high-grade squamous intraepithelial neoplasia; neoplasia is a large step toward cancerous growth known as a squamous cell carcinoma which contribute to all cervical, 70% of oropharyngeal, 78% of vaginal and 88% of anal cancers. This review will illuminate the relevance of CD4
MeSH term(s)	Female ; Humans ; Papillomavirus Infections/prevention & control ; Human Papillomavirus Viruses ; Papillomavirus Vaccines ; T-Lymphocytes ; CD4-Positive T-Lymphocytes
Chemical Substances	Papillomavirus Vaccines
Language	English
Publishing date	2023-05-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1111/imcb.12650
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Article ; Online: Navigating the complexity of chronic HIV-1 associated immune dysregulation.

Boyd, Mollie Aa / van Bockel, David / Munier, Cynthia Mee Ling / Kelleher, Anthony D

Current opinion in immunology

2022 Volume 76, Page(s) 102186

Abstract: Despite successful viral suppression with antiretroviral therapy, chronic HIV-1 infection is associated with ongoing immune dysfunction. Investigation of the complex immune response in treated and untreated individuals with chronic HIV-1 infection is ... ...

Abstract	Despite successful viral suppression with antiretroviral therapy, chronic HIV-1 infection is associated with ongoing immune dysfunction. Investigation of the complex immune response in treated and untreated individuals with chronic HIV-1 infection is warranted. Immune alterations such as monocyte phenotype and Th-17/Treg ratios often persist years after the reduction in viraemia and predispose many individuals to long-term comorbidities such as cardiovascular disease or cancer. Furthermore, while there has been extensive research on the latent reservoir of treated patients with chronic HIV-1, which prevents the discontinuation of treatment, the mechanism behind this remains elusive and needs further investigation. In this review, we assist in navigating the recent research on these groups of individuals and provide a basis for further investigation.
MeSH term(s)	CD4-Positive T-Lymphocytes ; HIV Infections/drug therapy ; HIV-1 ; Humans ; Monocytes
Language	English
Publishing date	2022-05-11
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2022.102186
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Article ; Online: Parallel analysis of multiple human memory CD4

Cook, Laura / Zaunders, John / Seddiki, Nabila / van Bockel, David / Kelleher, Anthony D / Munier, C Mee Ling

Immunology and cell biology

2022 Volume 101, Issue 2, Page(s) 171–178

Abstract: Activation induced marker (AIM) assays are being used increasingly to measure antigen-specific T-cell responses, but this activation can alter cell lineage defining phenotypic markers. We aimed to extend the utility of AIM assays to enable pre-activation ...

Abstract	Activation induced marker (AIM) assays are being used increasingly to measure antigen-specific T-cell responses, but this activation can alter cell lineage defining phenotypic markers. We aimed to extend the utility of AIM assays to enable pre-activation defined cell populations to be tracked and quantified within T-cell memory responses. We sorted three ex vivo CD4
MeSH term(s)	Humans ; T-Lymphocytes, Regulatory ; Coloring Agents/metabolism ; T-Lymphocyte Subsets ; CD4-Positive T-Lymphocytes ; Antigens/metabolism ; Cell Proliferation ; Forkhead Transcription Factors/metabolism
Chemical Substances	Coloring Agents ; Antigens ; Forkhead Transcription Factors
Language	English
Publishing date	2022-11-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1111/imcb.12606
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Article ; Online: Biomarkers of treatment success in fully sensitive pulmonary tuberculosis patients: a multicenter longitudinal study.

Nikolayevskyy, Vladyslav / Balabanova, Yanina / Kontsevaya, Irina / Ignatyeva, Olga / Skenders, Girts / Vasiliauskiene, Edita / Bockel, David van / Drobniewski, Francis

Biomarkers in medicine

2020 Volume 14, Issue 15, Page(s) 1439–1452

Abstract: Aim: ...

Abstract	Aim:
MeSH term(s)	Adult ; Antitubercular Agents/therapeutic use ; Biomarkers, Pharmacological/blood ; Cohort Studies ; Cytokines/blood ; Female ; Humans ; Intracellular Signaling Peptides and Proteins/analysis ; Intracellular Signaling Peptides and Proteins/blood ; Longitudinal Studies ; Lymphocyte Antigen 96/analysis ; Lymphocyte Antigen 96/blood ; Male ; Middle Aged ; Mycobacterium tuberculosis/pathogenicity ; Treatment Outcome ; Tuberculosis/drug therapy ; Tuberculosis, Pulmonary/blood ; Tuberculosis, Pulmonary/drug therapy ; Tuberculosis, Pulmonary/immunology
Chemical Substances	Antitubercular Agents ; Biomarkers, Pharmacological ; Cytokines ; Intracellular Signaling Peptides and Proteins ; LY96 protein, human ; Lymphocyte Antigen 96 ; TOLLIP protein, human
Language	English
Publishing date	2020-11-03
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2481014-9
ISSN	1752-0371 ; 1752-0363
ISSN (online)	1752-0371
ISSN	1752-0363
DOI	10.2217/bmm-2020-0246
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Article: Innate and Adaptive Immunity in Long-Term Non-Progression in HIV Disease.

Zaunders, John / van Bockel, David

Frontiers in immunology

2013 Volume 4, Page(s) 95

Abstract: Long-term non-progressors (LTNP) were identified after 10-15 years of the epidemic, and have been the subject of intense investigation ever since. In a small minority of cases, infection with nef/3'LTR deleted attenuated viral strains allowed control ... ...

Abstract	Long-term non-progressors (LTNP) were identified after 10-15 years of the epidemic, and have been the subject of intense investigation ever since. In a small minority of cases, infection with nef/3'LTR deleted attenuated viral strains allowed control over viral replication. A common feature of LTNP is the readily detected proliferation of CD4 T-cells in vitro, in response to p24. In some cases, the responding CD4 T-cells have cytotoxic effector function and may target conserved p24 epitopes, similar to the CD8 T-cells described below. LTNP may also carry much lower HIV DNA burden in key CD4 subsets, presumably resulting from lower viral replication during primary infection. Some studies, but not others, suggest that LTNP have CD4 T-cells that are relatively resistant to HIV infection in vitro. One possible mechanism may involve up-regulation of the cell cycle regulator p21/waf in CD4 T-cells from LTNP. Delayed progression in Caucasian LTNP is also partly associated with heterozygosity of the Δ32 CCR5 allele, probably through decreased expression of CCR5 co-receptor on CD4 T-cells. However, in approximately half of Caucasian LTNP, two host genotypes, namely HLA-B57 and HLA-B27, are associated with viral control. Immunodominant CD8 T-cells from these individuals target epitopes in p24 that are highly conserved, and escape mutations have significant fitness costs to the virus. Furthermore, recent studies have suggested that these CD8 T-cells from LTNP, but not from HLA-B27 or HLA-B57 progressors, can cross-react with intermediate escape mutations, preventing full escape via compensatory mutations. Humoral immunity appears to play little part in LTNP subjects, since broadly neutralizing antibodies are rare, even amongst slow progressors. Recent genome-wide comparisons between LTNP and progressors have confirmed the HLA-B57, HLA-B27, and delta32 CCR5 allelic associations, plus indicated a role for HLA-C/KIR interactions, but have not revealed any new genotypes so far. Nevertheless, it is hoped that studying the mechanisms of intracellular restriction factors, such as the recently identified SAMHD1, will lead to a better understanding of non-progression.
Language	English
Publishing date	2013-04-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2013.00095
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Article: Cytotoxic CD4 T Cells-Friend or Foe during Viral Infection?

Juno, Jennifer A / van Bockel, David / Kent, Stephen J / Kelleher, Anthony D / Zaunders, John J / Munier, C Mee Ling

Frontiers in immunology

2017 Volume 8, Page(s) 19

Abstract: CD4 T cells with cytotoxic function were once thought to be an artifact due to long- ... ...

Abstract	CD4 T cells with cytotoxic function were once thought to be an artifact due to long-term
Language	English
Publishing date	2017
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2017.00019
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Article: Circulating gluten-specific, but not CMV-specific, CD39

Cook, Laura / Munier, C Mee Ling / Seddiki, Nabila / Hardy, Melinda Y / Anderson, Robert P / Zaunders, John / Tye-Din, Jason A / Kelleher, Anthony D / van Bockel, David

Clinical & translational immunology

2020 Volume 9, Issue 1, Page(s) e1096

Abstract: Objectives: Understanding the T cell receptor (TCR) repertoire of regulatory CD4: Methods: We used the OX40 assay to isolate antigen-specific Tregs by induced surface co-expression of CD25, OX40 and CD39. RACE PCR amplification and Sanger sequencing ... ...

Abstract	Objectives: Understanding the T cell receptor (TCR) repertoire of regulatory CD4 Methods: We used the OX40 assay to isolate antigen-specific Tregs by induced surface co-expression of CD25, OX40 and CD39. RACE PCR amplification and Sanger sequencing of the TCR β chain were used to analyse repertoire diversity. Results: We found that, following oral gluten challenge, circulating gluten-specific CD39 Discussion: These data indicate that a biased TCR repertoire is not inherent to CD39 Conclusion: This is the first assessment of the TCR repertoire within circulating human Tregs specific for foreign antigen. These data enhance our understanding of antigen-specific CD4
Language	English
Publishing date	2020-01-12
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2694482-0
ISSN	2050-0068
ISSN	2050-0068
DOI	10.1002/cti2.1096
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Evaluation of Commercially Available Viral Transport Medium (VTM) for SARS-CoV-2 Inactivation and Use in Point-of-Care (POC) Testing.

van Bockel, David / Munier, C Mee Ling / Turville, Stuart / Badman, Steven G / Walker, Gregory / Stella, Alberto Ospina / Aggarwal, Anupriya / Yeang, Malinna / Condylios, Anna / Kelleher, Anthony D / Applegate, Tanya L / Vallely, Andrew / Whiley, David / Rawlinson, William / Cunningham, Phillip / Kaldor, John / Guy, Rebecca

Viruses

2020 Volume 12, Issue 11

Abstract: Critical to facilitating SARS-CoV-2 point-of-care (POC) testing is assurance that viruses present in specimens are inactivated onsite prior to processing. Here, we conducted experiments to determine the virucidal activity of commercially available Viral ... ...

Abstract	Critical to facilitating SARS-CoV-2 point-of-care (POC) testing is assurance that viruses present in specimens are inactivated onsite prior to processing. Here, we conducted experiments to determine the virucidal activity of commercially available Viral Transport Mediums (VTMs) to inactivate SARS-CoV-2. Independent testing methods for viral inactivation testing were applied, including a previously described World Health Organization (WHO) protocol, in addition to a buffer exchange method where the virus is physically separated from the VTM post exposure. The latter method enables sensitive detection of viral viability at higher viral titre when incubated with VTM. We demonstrate that VTM formulations, Primestore
MeSH term(s)	Betacoronavirus/isolation & purification ; COVID-19 Testing ; Clinical Laboratory Techniques ; Coronavirus Infections/diagnosis ; Culture Media/analysis ; Culture Media/pharmacology ; Humans ; Point-of-Care Testing/standards ; SARS-CoV-2 ; Specimen Handling/methods ; Specimen Handling/standards ; Viral Load/drug effects ; Virus Inactivation/drug effects
Chemical Substances	Culture Media
Keywords	covid19
Language	English
Publishing date	2020-10-23
Publishing country	Switzerland
Document type	Evaluation Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12111208
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: HIV-1 DNA Is Maintained in Antigen-Specific CD4+ T Cell Subsets in Patients on Long-Term Antiretroviral Therapy Regardless of Recurrent Antigen Exposure.

Hey-Nguyen, William J / Bailey, Michelle / Xu, Yin / Suzuki, Kazuo / Van Bockel, David / Finlayson, Robert / Leigh Brown, Andrew / Carr, Andrew / Cooper, David A / Kelleher, Anthony D / Koelsch, Kersten K / Zaunders, John J

AIDS research and human retroviruses

2018 Volume 35, Issue 1, Page(s) 112–120

Abstract: Memory CD4+ T cells (mCD4s) containing integrated HIV DNA are considered the main barrier to a cure for HIV infection. Here, we analyzed HIV DNA reservoirs in antigen-specific subsets of mCDs to delineate the mechanisms by which HIV reservoirs persist ... ...

Abstract	Memory CD4+ T cells (mCD4s) containing integrated HIV DNA are considered the main barrier to a cure for HIV infection. Here, we analyzed HIV DNA reservoirs in antigen-specific subsets of mCDs to delineate the mechanisms by which HIV reservoirs persist during antiretroviral therapy (ART). HIV Gag, cytomegalovirus (CMV), and tetanus toxoid (TT)-specific mCD4s were isolated from peripheral blood samples obtained from 11 individual subjects, 2-11 years after commencing ART. Antigen-specific mCD4s were identified by the sensitive OX40 assay and purified by cell sorting. Total HIV DNA levels were quantified by real-time PCR, and clonal viral sequences generated from mCD4 subsets and pre-ART plasma samples. Quantitative results and sequence analysis were restricted to five and three study participants, respectively, which was likely due to the low frequency of the antigen-specific mCD4s and relatively low HIV DNA proviral loads. Median HIV Gag-, CMV-, and TT-specific mCD4s were 0.61%, 2.46%, and 0.78% of total mCD4s, and they contained a median of 2.50, 2.38, and 2.55 log
MeSH term(s)	Adult ; Anti-Retroviral Agents/therapeutic use ; CD4-Positive T-Lymphocytes/virology ; DNA, Viral/analysis ; Female ; HIV Infections/drug therapy ; HIV Infections/virology ; HIV-1/genetics ; Humans ; Male ; Middle Aged ; Real-Time Polymerase Chain Reaction ; T-Lymphocyte Subsets/virology ; Viral Load
Chemical Substances	Anti-Retroviral Agents ; DNA, Viral
Language	English
Publishing date	2018-12-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639130-8
ISSN	1931-8405 ; 0889-2229
ISSN (online)	1931-8405
ISSN	0889-2229
DOI	10.1089/AID.2018.0235
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Article: Evaluation of Commercially Available Viral Transport Medium (VTM) for SARS-CoV-2 Inactivation and Use in Point-of-Care (POC) Testing

van Bockel, David / Munier, C. Mee Ling / Turville, Stuart / Badman, Steven G / Walker, Gregory / Stella, Alberto Ospina / Aggarwal, Anupriya / Yeang, Malinna / Condylios, Anna / Kelleher, Anthony D / Applegate, Tanya L / Vallely, Andrew / Whiley, David / Rawlinson, William / Cunningham, Phillip / Kaldor, John / Guy, Rebecca

Viruses. 2020 Oct. 23, v. 12, no. 11

2020

Abstract	Critical to facilitating SARS-CoV-2 point-of-care (POC) testing is assurance that viruses present in specimens are inactivated onsite prior to processing. Here, we conducted experiments to determine the virucidal activity of commercially available Viral Transport Mediums (VTMs) to inactivate SARS-CoV-2. Independent testing methods for viral inactivation testing were applied, including a previously described World Health Organization (WHO) protocol, in addition to a buffer exchange method where the virus is physically separated from the VTM post exposure. The latter method enables sensitive detection of viral viability at higher viral titre when incubated with VTM. We demonstrate that VTM formulations, Primestore® Molecular Transport Medium (MTM) and COPAN eNAT™ completely inactivate high-titre SARS-CoV-2 virus (>1 × 10⁷ copies/mL) and are compatible with POC processing. Furthermore, full viral inactivation was rapidly achieved in as little as 2 min of VTM exposure. We conclude that adding certain VTM formulations as a first step post specimen collection will render SARS-CoV-2 non-infectious for transport, or for further in-field POC molecular testing using rapid turnaround GeneXpert platforms or equivalent.
Keywords	Severe acute respiratory syndrome coronavirus 2 ; antiviral properties ; point-of-care systems ; viability ; viral load ; viruses
Language	English
Dates of publication	2020-1023
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v12111208
Database	NAL-Catalogue (AGRICOLA)

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