HIV-2 infection in the majority of infected subjects follows an attenuated disease course that distinguishes it from infection with HIV-1. Antigen-specific T cells are pivotal in the management of chronic viral infections but are not sufficient to control viral replication in HIV-1–positive subjects, and their function in HIV-2 infection is not fully established. In a community-based cohort of HIV-2 long-term nonprogressors in rural Guinea-Bissau, we performed what we believe is the first comprehensive analysis of HIV-2–specific immune responses. We demonstrate that Gag is the most immunogenic protein. The magnitude of the IFN-γ immune response to the HIV-2 proteome was inversely correlated with HIV-2 viremia, and this relationship was specifically due to the targeting of Gag. Furthermore, patients with undetectable viremia had greater Gag-specific responses compared with patients with high viral replication. The most frequently recognized peptides clustered within a defined region of Gag, and responses to a single peptide in this region were associated with low viral burden. The consistent relationship between Gag-specific immune responses and viremia control suggests that T cell responses are vital in determining the superior outcome of HIV-2 infection. A better understanding of how HIV-2 infection is controlled may identify correlates of effective protective immunity essential for the design of HIV vaccines.
Aleksandra Leligdowicz, Louis-Marie Yindom, Clayton Onyango, Ramu Sarge-Njie, Abraham Alabi, Matthew Cotten, Tim Vincent, Carlos da Costa, Peter Aaby, Assan Jaye, Tao Dong, Andrew McMichael, Hilton Whittle, Sarah Rowland-Jones
Title and authors | Publication | Year |
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Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS
Boswell MT, Nazziwa J, Kuroki K, Palm A, Karlson S, Månsson F, Biague A, da Silva ZJ, Onyango CO, de Silva TI, Jaye A, Norrgren H, Medstrand P, Jansson M, Maenaka K, Rowland-Jones SL, Esbjörnsson J |
Virus Evolution | 2022 |
A high prevalence of potential HIV elite controllers identified over 30 years in Democratic Republic of Congo
MG Berg, A Olivo, BJ Harris, MA Rodgers, L James, S Mampunza, J Niles, F Baer, J Yamaguchi, L Kaptue, O Laeyendecker, TC Quinn, C McArthur, GA Cloherty |
EBioMedicine | 2021 |
HIV-2-Infected Macrophages Produce and Accumulate Poorly Infectious Viral Particles
E Gea-Mallorquí, L Zablocki-Thomas, M Maurin, M Jouve, V Rodrigues, N Ruffin, P Benaroch |
Frontiers in microbiology | 2020 |
Delayed disease progression in HIV-2: the importance of TRIM5α and the retroviral capsid: Interaction of TRIM5α and HIV-2 CA
MT Boswell, SL Rowland-Jones |
Clinical & Experimental Immunology | 2019 |
Limited HIV-2 reservoirs in central-memory CD4 T-cells associated to CXCR6 co-receptor expression in attenuated HIV-2 infection
A Samri, C Charpentier, MS Diallo, M Bertine, S Even, V Morin, A Oudin, C Parizot, G Collin, A Hosmalin, R Cheynier, R Thiébaut, S Matheron, F Collin, R Zoorob, F Brun-Vézinet, B Autran, J Lifson |
PLoS pathogens | 2019 |
HIV-2 as a model to identify a functional HIV cure
J Esbjörnsson, M Jansson, S Jespersen, F Månsson, BL Hønge, J Lindman, C Medina, ZJ da Silva, H Norrgren, P Medstrand, SL Rowland-Jones, C Wejse |
AIDS Research and Therapy | 2019 |
Identification of Novel Respiratory Syncytial Virus CD4 + and CD8 + T Cell Epitopes in C57BL/6 Mice
ME Schmidt, SM Varga |
ImmunoHorizons | 2019 |
HLA-associated polymorphisms in the HIV-2 capsid highlight key differences between HIV-1 and HIV-2 immune adaptation:
TI de Silva, A Leligdowicz, J Carlson, M Garcia-Knight, C Onyango, N Miller, LM Yindom, S Hué, A Jaye, T Dong, M Cotten, SL Rowland-Jones |
AIDS | 2018 |
Elevated levels of invariant natural killer T-cell and natural killer cell activation correlate with disease progression in HIV-1 and HIV-2 infections:
SM Bächle, DF Malone, M Buggert, AC Karlsson, PE Isberg, AJ Biague, H Norrgren, P Medstrand, M Moll, JK Sandberg, M Jansson |
AIDS | 2016 |
Identification of Host Micro RNAs That Differentiate HIV-1 and HIV-2 Infection Using Genome Expression Profiling Techniques
K Devadas, S Biswas, M Haleyurgirisetty, V Ragupathy, X Wang, S Lee, I Hewlett |
Viruses | 2016 |
CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection:
M Buggert, J Frederiksen, O Lund, MR Betts, A Biague, M Nielsen, J Tauriainen, H Norrgren, P Medstrand, AC Karlsson, M Jansson |
AIDS | 2016 |
The presence of prolines in the flanking region of an immunodominant HIV-2 gag epitope influences the quality and quantity of the epitope generated: Antigen processing
S Jallow, A Leligdowicz, HB Kramer, C Onyango, M Cotten, C Wright, HC Whittle, A McMichael, T Dong, BM Kessler, SL Rowland-Jones |
European Journal of Immunology | 2015 |
Protection Versus Pathology in Aviremic and High Viral Load HIV-2 Infection--The Pivotal Role of Immune Activation and T-cell Kinetics
A Hegedus, S Nyamweya, Y Zhang, S Govind, R Aspinall, A Mashanova, VA Jansen, H Whittle, A Jaye, KL Flanagan, DC Macallan |
The Journal of Infectious Diseases | 2014 |
HIV-1 and HIV-2 Differentially Mature Plasmacytoid Dendritic Cells into IFN-Producing Cells or APCs
CM Royle, DR Graham, S Sharma, D Fuchs, A Boasso |
Journal of immunology (Baltimore, Md. : 1950) | 2014 |
HIV-2 and its role in conglutinated approach towards Acquired Immunodeficiency Syndrome (AIDS) Vaccine Development
B Diwan, R Saxena, A Tiwari |
SpringerPlus | 2013 |
Clinical predictors cannot replace biological predictors in HIV-2 infection in a community setting in West Africa
AJ Gourlay, C Tienen, SS Dave, T Vincent, SL Rowland-Jones, JR Glynn, HC Whittle, MF van der Loeff |
International Journal of Infectious Diseases | 2012 |
Are Plasma Biomarkers of Immune Activation Predictive of HIV Progression: A Longitudinal Comparison and Analyses in HIV-1 and HIV-2 Infections?
S Nyamweya, J Townend, A Zaman, SJ Steele, D Jeffries, S Rowland-Jones, H Whittle, KL Flanagan, A Jaye |
PloS one | 2012 |
For Protection from HIV-1 Infection, More Might Not Be Better: a Systematic Analysis of HIV Gag Epitopes of Two Alleles Associated with Different Outcomes of HIV-1 Infection
M Luo, CA Daniuk, TO Diallo, RE Capina, J Kimani, C Wachihi, M Kimani, T Bielawny, T Peterson, MG Mendoza, S Kiazyk, TB Ball, FA Plummer |
Journal of virology | 2011 |
Potent Autologous and Heterologous Neutralizing Antibody Responses Occur in HIV-2 Infection across a Broad Range of Infection Outcomes
TI de Silva, M Aasa-Chapman, M Cotten, S Hue, J Robinson, F Bibollet-Ruche, R Sarge-Njie, N Berry, A Jaye, P Aaby, H Whittle, S Rowland-Jones, R Weiss |
Journal of virology | 2011 |
Influence of HLA Class I and HLA-KIR Compound Genotypes on HIV-2 Infection and Markers of Disease Progression in a Manjako Community in West Africa
LM Yindom, A Leligdowicz, MP Martin, X Gao, Y Qi, SM Zaman, MS van der Loeff, C van Tienen, A Jaye, A Aveika, A Worwui, M Diatta, T Vincent, HC Whittle, SL Rowland-Jones, R Walton, M Carrington |
Journal of virology | 2010 |
Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village
MF van der Loeff, N Larke, S Kaye, N Berry, K Ariyoshi, A Alabi, C van Tienen, A Leligdowicz, R Sarge-Njie, Z da Silva, A Jaye, D Ricard, T Vincent, SR Jones, P Aaby, S Jaffar, H Whittle |
Retrovirology | 2010 |
HTLV-1 in rural Guinea-Bissau: prevalence, incidence and a continued association with HIV between 1990 and 2007
C van Tienen, MF van der Loeff, I Peterson, M Cotten, B Holmgren, S Andersson, T Vincent, R Sarge-Njie, S Rowland-Jones, A Jaye, P Aaby, H Whittle |
Retrovirology | 2010 |
Immune dysregulation in human immunodeficiency virus infection: know it, fix it, prevent it?
A Boasso, GM Shearer, C Chougnet |
Journal of Internal Medicine | 2009 |
Infants with late breast milk acquisition of HIV-1 generate interferon-gamma responses more rapidly than infants with early peripartum acquisition
B Lohman-Payne, JA Slyker, BA Richardson, C Farquhar, M Majiwa, E Maleche-Obimbo, D Mbori-Ngacha, J Overbaugh, S Rowland-Jones, G John-Stewart |
Clinical & Experimental Immunology | 2009 |
Downregulation of the T-Cell Receptor by Human Immunodeficiency Virus Type 2 Nef Does Not Protect against Disease Progression
J Feldmann, A Leligdowicz, A Jaye, T Dong, H Whittle, SL Rowland-Jones |
Journal of virology | 2009 |
Special Anniversary Review: Twenty-five years of human immunodeficiency virus research: successes and challenges
RA Weiss |
Clinical & Experimental Immunology | 2008 |
Higher Homologous and Lower Cross-Reactive Gag-Specific T-Cell Responses in Human Immunodeficiency Virus Type 2 (HIV-2) Than in HIV-1 Infection
W Jennes, M Camara, T Dièye, S Mboup, L Kestens |
Journal of virology | 2008 |
Gag-Specific CD4+ T-Cell Frequency Is Inversely Correlated with Proviral Load and Directly Correlated with Immune Activation in Infection with Human Immunodeficiency Virus Type 2 (HIV-2) but Not HIV-1
RB Foxall, CS Cortesão, AS Albuquerque, RS Soares, RM Victorino, AE Sousa |
Journal of virology | 2008 |