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  1. Article: Advancing HIV cure research in low- and middle-income countries requires empowerment of the next generation of scientists.

    Tatoud, Roger / Jones, R Brad / Dong, Krista / Ndung'u, Thumbi / Deeks, Steven / Tiemessen, Caroline T

    Journal of virus eradication

    2024  Volume 10, Issue 1, Page(s) 100364

    Abstract: While low- and middle-income countries (LMICs), especially in Southern and Eastern Africa, bear the largest burden of the HIV globally, investigators working on the front lines in these regions are leading a limited number of research efforts, ... ...

    Abstract While low- and middle-income countries (LMICs), especially in Southern and Eastern Africa, bear the largest burden of the HIV globally, investigators working on the front lines in these regions are leading a limited number of research efforts, particularly related to HIV cure. Conducting HIV cure research in high-burden HIV LIMCs provides an unparalleled opportunity to formulate innovative research strategies, design trials tailored to the local context, evaluate clinical outcomes within key and vulnerable populations, meaningful involvement of stakeholders, and to shape policies in areas where HIV prevention and cure interventions can yield the most significant impact. Further, the high prevalence of infection, with varied HIV strains affecting large diverse populations, creates a unique environment for studies that would not be feasible in any other part of the world. This underscores the critical importance of addressing obstacles to unlock the full potential of research efforts in these regions. In this viewpoint, we identify significant challenges facing early career investigators in LMICs, particularly in Africa, that hinder their full engagement in HIV cure research. Drawing examples from the International AIDS Society's Research-for-Cure Academy, we provide practical recommendations to overcome barriers that include limited access to funding, effective mentors, educational and career development opportunities, coupled with inadequate investment in infrastructure that contribute towards the limited number of investigators from high-burden HIV LIMCs who are spearheading cutting-edge cure research. Addressing these challenges is crucial to empower investigators who possess unique insights and expertise, and who are well positioned to lead HIV cure-related research efforts. We acknowledge and welcome initiatives that promote capacity building and knowledge exchange between early-career investigators in LMICs and their peers and scientific leaders from high-income countries (HICs). Prioritizing investment in global collaboration and partnership will play a pivotal role in empowering the next generation of African scientists and clinicians. To expedite advancements of cure-related strategies that will be effective in high-burden HIV LMICs, we endorse the sustainable expansion of these pivotal initiatives in these regions, to enhance their effectiveness and hasten progress in the pursuit of a global HIV cure.
    Language English
    Publishing date 2024-03-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2868549-0
    ISSN 2055-6659 ; 2055-6640
    ISSN (online) 2055-6659
    ISSN 2055-6640
    DOI 10.1016/j.jve.2024.100364
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Genetic variation of the HIV-1 subtype C transmitted/founder viruses long terminal repeat elements and the impact on transcription activation potential and clinical disease outcomes.

    Madlala, Paradise / Mkhize, Zakithi / Naicker, Shamara / Khathi, Samukelisiwe P / Maikoo, Shreyal / Gopee, Kasmira / Dong, Krista L / Ndung'u, Thumbi

    PLoS pathogens

    2023  Volume 19, Issue 6, Page(s) e1011194

    Abstract: A genetic bottleneck is a hallmark of HIV-1 transmission such that only very few viral strains, termed transmitted/founder (T/F) variants establish infection in a newly infected host. Phenotypic characteristics of these variants may determine the ... ...

    Abstract A genetic bottleneck is a hallmark of HIV-1 transmission such that only very few viral strains, termed transmitted/founder (T/F) variants establish infection in a newly infected host. Phenotypic characteristics of these variants may determine the subsequent course of disease. The HIV-1 5' long terminal repeat (LTR) promoter drives viral gene transcription and is genetically identical to the 3' LTR. We hypothesized that HIV-1 subtype C (HIV-1C) T/F virus LTR genetic variation is a determinant of transcriptional activation potential and clinical disease outcome. The 3'LTR was amplified from plasma samples of 41 study participants acutely infected with HIV-1C (Fiebig stages I and V/VI). Paired longitudinal samples were also available at one year post-infection for 31 of the 41 participants. 3' LTR amplicons were cloned into a pGL3-basic luciferase expression vector, and transfected alone or together with Transactivator of transcription (tat) into Jurkat cells in the absence or presence of cell activators (TNF-α, PMA, Prostratin and SAHA). Inter-patient T/F LTR sequence diversity was 5.7% (Renge: 2-12) with subsequent intrahost viral evolution observed in 48.4% of the participants analyzed at 12 months post-infection. T/F LTR variants exhibited differential basal transcriptional activity, with significantly higher Tat-mediated transcriptional activity compared to basal (p<0.001). Basal and Tat-mediated T/F LTR transcriptional activity showed significant positive correlation with contemporaneous viral loads and negative correlation with CD4 T cell counts (p<0.05) during acute infection respectively. Furthermore, Tat-mediated T/F LTR transcriptional activity significanly correlated positively with viral load set point and viral load; and negatively with CD4 T cell counts at one year post infection (all p<0.05). Lastly, PMA, Prostratin, TNF-α and SAHA cell stimulation resulted in enhanced yet heterologous transcriptional activation of different T/F LTR variants. Our data suggest that T/F LTR variants may influence viral transcriptional activity, disease outcomes and sensitivity to cell activation, with potential implications for therapeutic interventions.
    MeSH term(s) Humans ; Transcriptional Activation ; HIV-1/physiology ; Transcription, Genetic ; tat Gene Products, Human Immunodeficiency Virus/genetics ; Tumor Necrosis Factor-alpha/metabolism ; HIV Long Terminal Repeat/genetics ; Genetic Variation ; HIV Infections/genetics ; Gene Expression Regulation, Viral
    Chemical Substances prostratin (60857-08-1) ; tat Gene Products, Human Immunodeficiency Virus ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2023-06-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011194
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses.

    Luthuli, Bonisile / Gounder, Kamini / Deymier, Martin J / Dong, Krista L / Balazs, Alejandro B / Mann, Jaclyn K / Ndung'u, Thumbi

    Virology

    2023  Volume 583, Page(s) 14–26

    Abstract: The genetic diversity of HIV impedes vaccine development. Identifying the viral properties of transmitted/founder (T/F) variants may provide a common vaccine target. To study the biological nature of T/F viruses, we constructed full-length clones from ... ...

    Abstract The genetic diversity of HIV impedes vaccine development. Identifying the viral properties of transmitted/founder (T/F) variants may provide a common vaccine target. To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. Eighteen full-length T/F clones were generated from 9 women and six chronic infection clones were from 2 individuals. All clones but one were non-recombinant subtype C. Three of the 5 T/F clones and 3 chronic clones tested replicated efficiently in PBMCs and utilised CCR5 coreceptor for cell entry. Transmitted/founder and chronic infection clones displayed heterogenous in vitro replicative capacity and resistance to type I interferon. T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. Our findings suggest MTF transmission may select viruses with compact envelopes.
    MeSH term(s) Humans ; Male ; Female ; HIV-1 ; Persistent Infection ; HIV Infections ; Clone Cells
    Language English
    Publishing date 2023-04-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2023.04.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Early Initiation of Antiretroviral Therapy Preserves the Metabolic Function of CD4+ T Cells in Subtype C Human Immunodeficiency Virus 1 Infection.

    Naidoo, Kewreshini K / Highton, Andrew J / Baiyegunhi, Omolara O / Bhengu, Sindiswa P / Dong, Krista L / Bunders, Madeleine J / Altfeld, Marcus / Ndung'u, Thumbi

    The Journal of infectious diseases

    2023  Volume 229, Issue 3, Page(s) 753–762

    Abstract: Background: Immune dysfunction often persists in people living with human immunodeficiency virus (HIV) who are on antiretroviral therapy (ART), clinically manifesting as HIV-1-associated comorbid conditions. Early ART initiation may reduce incidence of ... ...

    Abstract Background: Immune dysfunction often persists in people living with human immunodeficiency virus (HIV) who are on antiretroviral therapy (ART), clinically manifesting as HIV-1-associated comorbid conditions. Early ART initiation may reduce incidence of HIV-1-associated immune dysfunction and comorbid conditions. Immunometabolism is a critical determinant of functional immunity. We investigated the effect of HIV-1 infection and timing of ART initiation on CD4+ T cell metabolism and function.
    Methods: Longitudinal blood samples from people living with HIV who initiated ART during hyperacute HIV-1 infection (HHI; before peak viremia) or chronic HIV-1 infection (CHI) were assessed for the metabolic and immune functions of CD4+ T cells. Metabolite uptake and mitochondrial mass were measured using fluorescent analogues and MitoTracker Green accumulation, respectively, and were correlated with CD4+ T cell effector functions.
    Results: Initiation of ART during HHI prevented dysregulation of glucose uptake by CD4+ T cells, but glucose uptake was reduced before and after ART initiation in CHI. Glucose uptake positively correlated with interleukin-2 and tumor necrosis factor-α production by CD4+ T cells. CHI was associated with elevated mitochondrial mass in effector memory CD4+ T cells that persisted after ART and correlated with PD-1 expression.
    Conclusions: ART initiation in HHI largely prevented metabolic impairment of CD4+ T cells. ART initiation in CHI was associated with persistently dysregulated immunometabolism of CD4+ T cells, which was associated with impaired cellular functions and exhaustion.
    MeSH term(s) Humans ; CD4-Positive T-Lymphocytes ; HIV-1 ; Anti-Retroviral Agents/therapeutic use ; Anti-Retroviral Agents/pharmacology ; HIV Infections ; Glucose
    Chemical Substances Anti-Retroviral Agents ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2023-10-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiad432
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Centring the health of women across the HIV research continuum.

    Barr, Elizabeth / Marshall, Leslie J / Collins, Lauren F / Godfrey, Catherine / St Vil, Noelle / Stockman, Jamila K / Davey, Dvora L Joseph / Dong, Krista / Temkin, Sarah M / Glenshaw, Mary T / Byrd, Corette / Clayton, Janine A / Goodenow, Maureen M

    The lancet. HIV

    2024  Volume 11, Issue 3, Page(s) e186–e194

    Abstract: Despite tremendous advances in HIV research, women and gender diverse people-particularly women from racial and ethnic groups under-represented in research, transgender women, and young women-remain disproportionately affected by HIV. Women and gender ... ...

    Abstract Despite tremendous advances in HIV research, women and gender diverse people-particularly women from racial and ethnic groups under-represented in research, transgender women, and young women-remain disproportionately affected by HIV. Women and gender diverse people face unique challenges and have been under-represented in HIV research. The National Institutes of Health (NIH) is tasked to apply fundamental knowledge about the nature and behaviour of living systems to enhance health, lengthen life, and reduce disability. Rigorous exploration of-and interventions for-the individual, social, biological, structural, and environmental factors that influence HIV prevention, transmission, treatment, and cure is crucial to advance research for women, girls, and gender diverse people across the lifespan. In this Position Paper, we introduce a framework for an intersectional, equity-informed, data-driven approach to research on HIV and women and highlight selected issues for women and gender diverse people, including HIV prevention, HIV cure, ageing with HIV, substance use and misuse, violence, pregnancy, and breastfeeding or chestfeeding. This framework underlines a new HIV and Women Signature Programme from the NIH Office of AIDS Research and Office of Research on Women's Health that advances the NIH vision for women's health, in which all women receive evidence-based HIV prevention, treatment, and care across their lifespan tailored to their unique needs, circumstances, and goals. The time is now to centre the health of women, girls, and gender diverse people across the HIV research continuum.
    MeSH term(s) Humans ; Female ; HIV Infections/diagnosis ; HIV Infections/epidemiology ; HIV Infections/prevention & control ; Acquired Immunodeficiency Syndrome ; Women's Health ; Gender Identity ; Violence
    Language English
    Publishing date 2024-02-28
    Publishing country Netherlands
    Document type Journal Article ; Review
    ISSN 2352-3018
    ISSN (online) 2352-3018
    DOI 10.1016/S2352-3018(24)00004-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Generation and characterization of infectious molecular clones of transmitted/founder HIV-1 subtype C viruses

    Luthuli, Bonisile / Gounder, Kamini / Deymier, Martin J. / Dong, Krista L. / Balazs, Alejandro B. / Mann, Jaclyn K. / Ndung'u, Thumbi

    Virology. 2023 June, v. 583 p.14-26

    2023  

    Abstract: The genetic diversity of HIV impedes vaccine development. Identifying the viral properties of transmitted/founder (T/F) variants may provide a common vaccine target. To study the biological nature of T/F viruses, we constructed full-length clones from ... ...

    Abstract The genetic diversity of HIV impedes vaccine development. Identifying the viral properties of transmitted/founder (T/F) variants may provide a common vaccine target. To study the biological nature of T/F viruses, we constructed full-length clones from women detected during Fiebig stage I acute HIV-1 infection (AHI) from heterosexual male-to-female (MTF) transmission; and clones after one year of infection using In-Fusion-based cloning. Eighteen full-length T/F clones were generated from 9 women and six chronic infection clones were from 2 individuals. All clones but one were non-recombinant subtype C. Three of the 5 T/F clones and 3 chronic clones tested replicated efficiently in PBMCs and utilised CCR5 coreceptor for cell entry. Transmitted/founder and chronic infection clones displayed heterogenous in vitro replicative capacity and resistance to type I interferon. T/F viruses had shorter Env glycoproteins and fewer N-linked glycosylation sites in Env. Our findings suggest MTF transmission may select viruses with compact envelopes.
    Keywords HIV infections ; genetic variation ; glycoproteins ; glycosylation ; interferons ; vaccine development ; vaccines ; virology ; HIV-1 ; Subtype C ; Transmitted/founder ; Infectious molecular clones
    Language English
    Dates of publication 2023-06
    Size p. 14-26.
    Publishing place Elsevier Inc.
    Document type Article ; Online
    Note Use and reproduction
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2023.04.001
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Antigen Presenting Cells Contribute to Persistent Immune Activation Despite Antiretroviral Therapy Initiation During Hyperacute HIV-1 Infection.

    Naidoo, Kewreshini K / Ndumnego, Okechukwu C / Ismail, Nasreen / Dong, Krista L / Ndung'u, Thumbi

    Frontiers in immunology

    2021  Volume 12, Page(s) 738743

    Abstract: Human immunodeficiency virus (HIV)-induced changes in immune cells during the acute phase of infection can cause irreversible immunological damage and predict the rate of disease progression. Antiretroviral therapy (ART) remains the most effective ... ...

    Abstract Human immunodeficiency virus (HIV)-induced changes in immune cells during the acute phase of infection can cause irreversible immunological damage and predict the rate of disease progression. Antiretroviral therapy (ART) remains the most effective strategy for successful immune restoration in immunocompromised people living with HIV and the earlier ART is initiated after infection, the better the long-term clinical outcomes. Here we explored the effect of ART on peripheral antigen presenting cell (APC) phenotype and function in women with HIV-1 subtype C infection who initiated ART in the hyperacute phase (before peak viremia) or during chronic infection. Peripheral blood mononuclear cells obtained longitudinally from study participants were used for immunophenotyping and functional analysis of monocytes and dendritic cells (DCs) using multiparametric flow cytometry and matched plasma was used for measurement of inflammatory markers IL-6 and soluble CD14 (sCD14) by enzyme-linked immunosorbent assay. HIV infection was associated with expansion of monocyte and plasmacytoid DC (pDC) frequencies and perturbation of monocyte subsets compared to uninfected persons despite antiretroviral treatment during hyperacute infection. Expression of activation marker CD69 on monocytes and pDCs in early treated HIV was similar to uninfected individuals. However, despite early ART, HIV infection was associated with elevation of plasma IL-6 and sCD14 levels which correlated with monocyte activation. Furthermore, HIV infection with or without early ART was associated with downmodulation of the co-stimulatory molecule CD86. Notably, early ART was associated with preserved toll-like receptor (TLR)-induced IFN-α responses of pDCs. Overall, this data provides evidence of the beneficial impact of ART initiated in hyperacute infection in preservation of APC functional cytokine production activity; but also highlights persistent inflammation facilitated by monocyte activation even after prolonged viral suppression and suggests the need for therapeutic interventions that target residual immune activation.
    MeSH term(s) Adolescent ; Anti-Retroviral Agents/therapeutic use ; Antigens, CD/metabolism ; Antigens, Differentiation, T-Lymphocyte/metabolism ; B7-2 Antigen/metabolism ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD4-Positive T-Lymphocytes/virology ; Cytokines/metabolism ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Dendritic Cells/virology ; Female ; HIV Infections/drug therapy ; HIV Infections/immunology ; HIV Infections/virology ; HIV-1/drug effects ; HIV-1/immunology ; HIV-1/pathogenicity ; Host-Pathogen Interactions ; Humans ; Lectins, C-Type/metabolism ; Lipopolysaccharide Receptors/metabolism ; Longitudinal Studies ; Monocytes/drug effects ; Monocytes/immunology ; Monocytes/metabolism ; Monocytes/virology ; Phenotype ; Pilot Projects ; Time Factors ; Treatment Outcome ; Viral Load ; Young Adult
    Chemical Substances Anti-Retroviral Agents ; Antigens, CD ; Antigens, Differentiation, T-Lymphocyte ; B7-2 Antigen ; CD14 protein, human ; CD69 antigen ; CD86 protein, human ; Cytokines ; Lectins, C-Type ; Lipopolysaccharide Receptors
    Language English
    Publishing date 2021-09-24
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.738743
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: 'With this study, we have hope that something is coming': community members' perceptions of HIV cure-related research in Durban, South Africa - a qualitative focus group study.

    Dubé, Karine / Mthimkhulu, Deli / Ngcobo, Wiseman / Mindry, Deborah / Maphalala, Luyanda / Pillay, Vanessa / Tran, Whitney / Korolkova, Ana / Ndung'u, Thumbi / Dong, Krista

    HIV research & clinical practice

    2023  Volume 24, Issue 1, Page(s) 2243046

    Abstract: Background: Developing a cure for HIV remains a global scientific priority. In 2022, the Females Rising through Education, Support and Health (FRESH) cohort launched an HIV cure-related trial involving an analytical treatment interruption (ATI) in ... ...

    Abstract Background: Developing a cure for HIV remains a global scientific priority. In 2022, the Females Rising through Education, Support and Health (FRESH) cohort launched an HIV cure-related trial involving an analytical treatment interruption (ATI) in Durban, South Africa.
    Objectives: To explore community perspectives about HIV cure-related research.
    Methods: Between July-August 2022, we conducted three focus groups with community members. We transcribed audio recordings verbatim and used content analysis to analyze the data.
    Results: Twenty community members (13 women and 7 men) participated in three focus groups (HIV status not included). Participants viewed HIV cure-related research as a way to address the issue of defaulting on (not taking) HIV treatment. Participants expressed hesitancy around ATIs, since these contradict longstanding treatment adherence messages. Participants shared concerns around the risk of side effects from experimental interventions balanced against potential efficacy. They advocated for trial participants to have the right to decide whether to inform their sex partners about their HIV status and ATI participation, rather than research teams making disclosure mandatory. Focus group participants also emphasized the importance of using simple language to explain HIV cure-related research.
    Conclusions: With HIV cure trials set to launch across Africa in the future, there is a critical need to better understand and respond to local community needs and preferences and to adopt this as standard practice prior to regional trial implementation.
    MeSH term(s) Male ; Humans ; Female ; Focus Groups ; HIV Infections/drug therapy ; South Africa ; Qualitative Research ; Disclosure
    Language English
    Publishing date 2023-08-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2578-7470
    ISSN (online) 2578-7470
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Bringing social context into global biomedical HIV cure-related research: An urgent call to action.

    Miall, Annie / McLellan, Rio / Dong, Krista / Ndung'u, Thumbi / Saberi, Parya / Sauceda, John A / Dubé, Karine

    Journal of virus eradication

    2021  Volume 8, Issue 1, Page(s) 100062

    Abstract: Advances in science have ushered in a wave of new potential curative and control strategies for HIV that could eliminate the current requirement for life-long antiretroviral therapy (ART) for people living with HIV (PLWH). In this article, we argue that ... ...

    Abstract Advances in science have ushered in a wave of new potential curative and control strategies for HIV that could eliminate the current requirement for life-long antiretroviral therapy (ART) for people living with HIV (PLWH). In this article, we argue that it is critical to consider social contexts in the development of HIV cure trial protocols. The biological and behavioral risk factors for HIV acquisition by study participants are inseparable from the social context in which these participants live. The article discusses an example of a cohort established to further HIV cure research that included social context, called the FRESH Acute HIV study, which combines a sociostructural intervention while conducting HIV prevention, treatment and cure-related research in Durban, South Africa. We make an urgent call to action to include sociobehavioral components as instrumental in future HIV cure trials in global context.
    Language English
    Publishing date 2021-12-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2868549-0
    ISSN 2055-6659 ; 2055-6640
    ISSN (online) 2055-6659
    ISSN 2055-6640
    DOI 10.1016/j.jve.2021.100062
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Population-specific diversity of the immunoglobulin constant heavy G chain (IGHG) genes.

    Bashirova, Arman A / Zheng, Wanjing / Akdag, Marjan / Augusto, Danillo G / Vince, Nicolas / Dong, Krista L / O'hUigin, Colm / Carrington, Mary

    Genes and immunity

    2021  Volume 22, Issue 7-8, Page(s) 327–334

    Abstract: Human immunoglobulin G (IgG) molecules, IgG1, IgG2 and IgG3, exhibit substantial inter-individual variation in their constant heavy chain regions, as discovered by serological methods. This polymorphism is encoded by the IGHG1, IGHG2, and IGHG3 genes and ...

    Abstract Human immunoglobulin G (IgG) molecules, IgG1, IgG2 and IgG3, exhibit substantial inter-individual variation in their constant heavy chain regions, as discovered by serological methods. This polymorphism is encoded by the IGHG1, IGHG2, and IGHG3 genes and may influence antibody function. We sequenced the coding fragments of these genes in 95 European Americans, 94 African Americans, and 94 Black South Africans. Striking differences were observed between the population groups, including extremely low amino acid sequence variation in IGHG1 among South Africans, and higher IGHG2 and IGHG3 diversity in individuals of African descent compared to individuals of European descent. Molecular definition of the loci illustrates a greater level of allelic polymorphism than previously described, including the presence of common IGHG2 and IGHG3 variants that were indistinguishable serologically. Comparison of our data with the 1000 Genome Project sequences indicates overall agreement between the datasets, although some inaccuracies in the 1000 Genomes Project are likely. These data represent the most comprehensive analysis of IGHG polymorphisms across major populations, which can now be applied to deciphering their functional impact.
    MeSH term(s) Alleles ; Genes, Immunoglobulin ; Humans ; Immunoglobulin G/genetics ; Immunoglobulin Heavy Chains/genetics ; Polymorphism, Genetic
    Chemical Substances Immunoglobulin G ; Immunoglobulin Heavy Chains
    Language English
    Publishing date 2021-12-04
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 2060566-3
    ISSN 1476-5470 ; 1466-4879
    ISSN (online) 1476-5470
    ISSN 1466-4879
    DOI 10.1038/s41435-021-00156-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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