Marcus Altfeld

Heinrich Pette Institute – Leibniz Institute for Experimental Virology, Hamburg, Hamburg, Germany

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Publications (228)1737.54 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Much is known about the characteristics of broadly neutralizing antibodies (bNAbs) generated during HIV-1 infection, but little is known about immunological mechanisms responsible for their development in only a minority of those infected by HIV-1. By monitoring longitudinally a cohort of HIV-1 infected subjects, we observed that the preservation of CXCR5+ CD4+ T helper cell frequencies and activation status of B cells during the first year of infection correlates with the maximum breadth of plasma neutralizing antibody responses during chronic infection, independently of viral load. Although, during the first year of infection, no differences were observed in the abilities of peripheral CXCR5+ CD4+ T helper cells to induce antibody secretion by autologous naïve B cells, higher frequencies of class-switched antibodies were detected in co-cultures of CXCR5+ CD4+ T and B cells from the subjects who later developed broadly neutralizing antibody responses than those who did not. Furthermore, B cells from the former subjects had higher expression of AICDA than B cells from the latter subjects and transcript levels correlated with the frequency of CXCR5+ CD4+ T cells. Thus, the early preservation of CXCR5+ CD4+ T cells and B cell function are central to the development of bNAbs. Our study provides a possible explanation for their infrequent generation during HIV-1 infection.
    Journal of Virology 09/2014; · 5.08 Impact Factor
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    ABSTRACT: Events during primary HIV-1 infection have been shown to be critical for the subsequent rate of disease progression. Early control of viral replication, resolution of clinical symptoms and development of a viral setpoint have been associated with the emergence of HIV-specific CD8 T cell responses. Here we assessed which particular HIV-specific CD8 T cell responses contribute to long-term control of HIV-1.
    Journal of virology. 08/2014;
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    ABSTRACT: It is unknown whether the reduction in HIV-1 reservoirs seen after allogeneic hematopoietic stem cell transplantation (HSCT) with susceptible donor cells is sufficient to achieve sustained HIV-1 remission.
    Annals of internal medicine 07/2014; · 13.98 Impact Factor
  • Jan van Lunzen, Marcus Altfeld
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    ABSTRACT: Women and men are different-and this fundamental observation extends to their susceptibility and response to different diseases, including autoimmune and infectious diseases. Apart from cultural and behavioral differences between the sexes that play a prominent role in the exposure to pathogens, increasing data show that women and men also differ in their immune responses to infections. This applies to infections with viruses, bacteria, and parasites, including the pathogens most relevant for human health, causing malaria, tuberculosis, AIDS, hepatitis, and influenza. Only recently, the biological pathways responsible for these sex-based differences in the manifestations of infectious diseases have been started to be unveiled. These include immunological pathways affected by sex hormones, as well as consequences of differential expression of X-chromosome-encoded genes on immune responses to pathogens. Further research is required to gain a better understanding of the differences in immunity to infections between women and men in order to develop individualized treatment concepts in infectious diseases that take sex-specific host factors into account.
    The Journal of infectious diseases. 07/2014; 209 Suppl 3:S79-80.
  • Marylyn M Addo, Marcus Altfeld
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    ABSTRACT: Human immunodeficiency virus (HIV) remains a global infectious diseases threat that disproportionally affects women. Beyond social and political factors, biological and genetic differences have been identified that lead to differential disease courses and outcomes in men and women. Following HIV type 1 (HIV-1) seroconversion, women have up to 40% lower HIV loads and higher CD4(+) T-cell counts than men. However, at the same level of viremia, progression to AIDS is faster in women. After adjustment for viral load, HIV-positive women also display increased levels of generalized immune activation and experience the consequences of elevated inflammatory activity more frequently than men. Part of these observations are linked to sex-based differences in innate immunity, in which the differential ability of plasmacytoid dendritic cells to produce interferon α following stimulation of Toll-like receptor 7 and upregulation of interferon-stimulated genes play a central role. Here, we review the current knowledge and remaining gaps therein regarding sex-based differences in HIV-1 pathogenesis.
    The Journal of infectious diseases. 07/2014; 209 Suppl 3:S86-92.
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    ABSTRACT: This study assessed cellular and soluble markers of immune activation in HIV-1 seronegative MSM. MSM immune profiles were characterized by an increased expression of CD57 on T cells and endotoxemia. Endotoxin presence was linked to recent high-risk exposure and associated with elevated cytokine levels and decreased CD4/CD8 T cell ratios. Taken together, these data show elevated levels of inflammation linked to periods of endotoxemia resulting in a significantly different immune phenotype in a subset of MSM at a high risk of HIV-1 acquisition.
    AIDS (London, England) 07/2014; · 4.91 Impact Factor
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    ABSTRACT: The acquisition and maintenance of NK-cell function is mediated by inhibitory killer-cell immunoglobulin-like receptors (KIRs) through their interaction with HLA class I molecules. Recently, HLA-C expression levels were shown to be correlated with protection against multiple outcomes of HIV-1 infection; however the underlying mechanisms are poorly understood. As HLA-C is the natural ligand for the inhibitory receptors KIR2DL1 and KIR2DL2/3, we sought to determine whether HLA-C group haplotypes affect NK-cell responses during primary HIV-1 infection. The phenotypes and functional capacity of NK cells derived from HIV-1-positive and HIV-1-negative individuals were assessed (N = 42 and N = 40, respectively). HIV-1 infection was associated with an increased frequency of KIR2DL1–3+ NK cells. Further analysis showed that KIR2DL1+ NK cells were selectively increased in individuals homozygous for HLA-C2, while HLA-C1-homozygous individuals displayed increased proportions of KIR2DL2/3+ NK cells. KIR2DL1–3+ NK cells were furthermore more polyfunctional during primary HIV-1 infection in individuals also encoding for their cognate HLA-C group haplotypes, as measured by degranulation and IFN-γ and TNF-α production. These results identify a novel relationship between HLA-C and KIR2DL+ NK-cell subsets and demonstrate that HLA-C-mediated licensing modulates NK-cell responses to primary HIV-1 infection.This article is protected by copyright. All rights reserved
    European Journal of Immunology 07/2014; · 4.97 Impact Factor
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    ABSTRACT: Increasing data suggest that NK cells can mediate antiviral activity in HIV-1-infected humans, and as such, novel approaches harnessing the anti-HIV-1 function of both T cells and NK cells represent an attractive option to improve future HIV-1 immunotherapies. Chronic progressive HIV-1 infection has been associated with a loss of CD4+ T helper cell function and with the accumulation of anergic NK cells. As several studies have suggested that cytokines produced by CD4+ T cells are required to enhance NK cell function in various infection models, we hypothesized that reconstitution of HIV-1-specific CD4+ T cell responses by therapeutic immunization would restore NK cell activity in infected individuals. Using flow cytometry, we examined the function of CD4+ T cells and NK cells in response to HIV-1 in subjects with treated chronic HIV-1 infection before and after immunization with an adjuvanted HIV-1 Gp120/NefTat subunit protein vaccine candidate provided by GlaxoSmithKline. Vaccination induced an increased expression of IL-2 by Gp120-specific CD4+ T cells in response to HIV-1 peptides ex vivo, which was associated with an enhanced production of IFN-γ by NK cells. Our data show that reconstitution of HIV-1-specific CD4+ T cell function by therapeutic immunization can enhance NK cell activity in HIV-1-infected individuals. NK cells are effector cells of the innate immune system and are important in the control of viral infection. Recent studies have demonstrated the crucial role played by NK cells in controlling and/or limiting acquisition of HIV-1 infection. However, NK cell function is impaired during progressive HIV-1 infection. We recently showed that therapeutic immunization of treated HIV-1-infected individuals reconstituted strong T-cell responses, measured notably by their production of IL-2, a cytokine that can activate NK cells. The current study suggests that reconstitution of T cell function by therapeutic vaccination can enhance NK cell activity in individuals with chronic HIV-1 infection. Our findings provide new insights into the interplay between adaptive and innate immune mechanisms involved in HIV-1 immunity, and unveil opportunities to harness NK cell function in future therapeutic vaccine strategies to target HIV-1.
    Journal of Virology 05/2014; · 5.08 Impact Factor
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    ABSTRACT: The aim of this study was to assess the consequence of sequence variations in HLA-C03:04-presented HIV-1 p24 Gag epitopes on binding of the inhibitory natural killer (NK) cell receptor KIR2DL2 to HLA-C03:04. HIV-1 may possibly evade recognition by KIR+ NK cells through selection of sequence variants that interfere with the interactions of inhibitory killer cell immunoglobulin-like receptors (KIRs) and their target ligands on HIV-1 infected cells. KIR2DL2 is an inhibitory NK cell receptor that binds to a family of HLA-C ligands. Here, we investigated whether HIV-1 encodes for HLA-C03:04-restricted epitopes that alter KIR2DL2 binding. Tapasin-deficient 721.220 cells expressing HLA-C03:04 were pulsed with overlapping peptides (10mers overlapped by nine amino acids, spanning the entire HIV-1 p24 Gag sequence) to identify peptides that stabilized HLA-C expression. Then, the impact that sequence variation in HLA-C03:04-binding HIV-1 epitopes has on KIR2DL2 binding and KIR2DL2+ NK cell function was determined using KIR2DL2-Fc constructs and NK cell degranulation assays. Several novel HLA-C03:04 binding epitopes were identified within the HIV-1 p24 Gag consensus sequence. Three of these consensus sequence peptides (Gag144-152, Gag163-171 and Gag295-304) enabled binding of KIR2DL2 to HLA-C03:04 and resulted in inhibition of KIR2DL2+ primary NK cells. Furthermore, naturally occurring minor variants of epitope Gag295-304 enhanced KIR2DL2 binding to HLA-C03:04. Our data show that naturally occurring sequence variations within HLA-C03:04-restricted HIV-1 p24 Gag epitopes can have a significant impact on the binding of inhibitory KIR receptors and primary NK cell function.
    AIDS (London, England) 04/2014; · 4.91 Impact Factor
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    ABSTRACT: Inflammation in early HIV-1 disease progression is not well-characterized. Patients with untreated primary HIV-1 infection (N=90) were studied to determine associations of inflammatory proteins with early disease progression. High plasma TNFα levels (≥8.5 pg/mL) were significantly associated with increased viral load set point, and shorter time to CD4(+)T-cell count <500 cells/mm(3) and initiation of antiretroviral therapy(ART). Increased risk of reaching CD4(+)T-cell count<500 cells/mm(3) in the high TNFα group was driven by viral load but independent of concurrent CD4(+)T-cell count. Thus, TNFα appears to be an important mediator of inflammation in patients with poor viral control and early HIV-1 disease progression.
    The Journal of Infectious Diseases 03/2014; · 5.85 Impact Factor
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    ABSTRACT: The antiviral role of TRIM E3 ligases in vivo is not fully understood. To test the hypothesis that TRIM5α and TRIM22 have differential transcriptional regulation and distinct anti-HIV roles according to infection phase and compartment, we measured TRIM5α, TRIM22 and type 1 interferon (IFN-1)-inducible MxA levels in peripheral blood mononuclear cells (PBMCs) during primary and chronic HIV-1 infection, and in matched PBMCs and central nervous system (CNS)-derived cells. Associations with biomarkers of disease progression were explored. The impact of IFN-1, select pro-inflammatory cytokines and HIV on TRIM E3 ligase-specific expression was investigated. PBMCs from individuals with primary and chronic HIV-1 infection had significantly higher levels of MxA and TRIM22 compared to HIV-1 negative PBMCs (P < 0.05, all comparisons). PBMCs from chronic infection had lower levels of TRIM5α compared to primary infection or HIV-1 uninfected (both P = 0.0001). In matched CNS-derived samples and PBMCs, higher levels of MxA (P = 0.001) and TRIM5α (P = 0.0001) were noted in the CNS. There was negative correlation between TRIM22 levels in PBMC and plasma viral load (r = -0.40, P = 0.04). In vitro, IFN-1 and rarely pro-inflammatory cytokines induced TRIM5α and TRIM22 in cell type-dependent manner and knockdown of either protein in CD4+ lymphocytes resulted in increased HIV-1 infection. These data suggest that there are infection-phase specific and anatomically compartmentalized differences in TRIM5α and TRIM22 regulation involving primarily IFN-1 and specific cell types, and indicate subtle differences in the antiviral role and transcriptional regulation of TRIM E3 ligases in vivo.Importance Interferon type I-inducible TRIM E3 ligases are a family of intracellular proteins with potent antiviral activities mediated through diverse mechanisms. However, little is known about the contribution of these proteins to antiviral immunity in vivo and how their expression is regulated. We show here that TRIM5α and TRIM22, two prominent members of the family, have different expression patterns in vivo and that expression pattern depends on HIV-1 infection status and phase. Furthermore, expression differs in peripheral blood versus central nervous system anatomical sites of infection. Only TRIM22 expression correlates negatively with HIV-1 viral load but gene silencing of both proteins enhances HIV-1 infection of target cells. We report on subtle differences in TRIM5α and TRIM22 gene induction by IFN-1 and pro-inflammatory cytokines in CD4+ lymphocytes, monocytes and neuronal cells. This study enhances our understanding of antiviral immunity by intrinsic antiviral factors and how their expression is determined.
    Journal of Virology 01/2014; · 5.08 Impact Factor
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    ABSTRACT: HLA-B alleles are associated with viral control in chronic HIV-1 infection, however, their role in primary HIV-1 disease is unclear. This study sought to determine the role of HLA-B alleles in viral control during the acute phase of HIV-1 infection and establishment of the early viral load set point (VLSP). Individuals identified during primary HIV-1 infection were HLA class I typed and followed longitudinally. Associations between HLA-B alleles and HIV-1 viral replication during acute infection and VLSP were analyzed in untreated subjects. The results showed that neither HLA-B*57 nor HLA-B*27 were significantly associated with viral control during acute HIV-1 infection (Fiebig stage I-IV, n=171). HLA-B*57 was however significantly associated with a subsequent lower VLSP (p<0.001, n=135) with nearly 1 log10 less median viral load. Analysis of a known polymorphism at position 97 of HLA-B showed significant associations with both lower initial viral load (p<0.01) and lower VLSP (p<0.05). However, this association was dependent on different amino acids at this position for each endpoint. The effect of HLA-B*57 on viral control is more pronounced during the later stages of primary HIV-1 infection, which suggests the underlying mechanism of control occurs at a critical period in the first several months after HIV-1 acquisition. The risk profile of polymorphisms at position 97 of HLA-B are more broadly associated with HIV-1 viral load during primary infection and may serve as a focal point in further studies of HLA-B function.
    Retrovirology 11/2013; 10(1):139. · 5.66 Impact Factor
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    ABSTRACT: To study the cytokine/chemokine profiles in response to HIV-1 viremia, and elucidate the pathways leading to HIV-1-induced inflammation. Plasma levels of 19 cytokines in individuals with early HIV-1 infection and individuals undergoing treatment interruptions were evaluated via multiplex assay. To investigate the cellular sources of relevant cytokines, sorted cells from HIV-1 infected individuals were assessed for mRNA expression. Relevant signaling pathways were assessed by comparing cytokine production patterns of peripheral blood mononuclear cells stimulated with intact HIV-1 or specific Toll-like receptor (TLR) stimulants with and without a TLR7/9 antagonist. IP-10 plasma concentration was most significantly associated with HIV-1 viral load and was the most significant contributor in a multivariate model. IP-10 mRNA was highly expressed in monocytes and mDCs and these cells were the dominant producers after in-vitro stimulation with TLR7/8 ligands (CL097 and ssRNAGag1166), AT-2 HIV-1, and HIV-1NL43 virus. Partial least square discriminant analysis of culture supernatants revealed distinct cytokine/chemokine secretion profiles associated with intact viruses compared with TLR7/8 ligands alone, with IP-10 production linked to the former. A TLR7/9 antagonist blocked IP-10 production following whole virus stimulation, suggesting the involvement of TLR7/9 in the recognition of HIV-1 by these cells. Monocytes and mDCs produce significant amounts of IP-10 in response to HIV-1 viremia and after in-vitro stimulation with HIV-1. Stimulation with HIV-1-derived TLR7/8-ligands versus HIV-1 resulted in distinct cytokine/chemokine profiles, indicating additional pathways other than TLR7/8 that lead to the activation of innate immune cells by HIV-1.
    AIDS (London, England) 10/2013; 27(16):2505-2517. · 4.91 Impact Factor
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    ABSTRACT: Natural killer (NK) cells constitutively express high levels of Tim-3, an immunoregulatory molecule recently proposed to be a marker for mature and functional NK cells. Whether HIV-1 infection modulates the expression of Tim-3 on NK cells, or the levels of its ligand Galectin-9 (Gal-9), and how signaling through these molecules affects the NK cell response to HIV-1 remains inadequately understood. We analyzed Tim-3 and Gal-9 expression in a cohort of 85 individuals with early and chronic HIV-1 infection, and in 13 HIV-1 seronegative control subjects. HIV-1 infection was associated with reduced expression of Tim-3 on NK cells, which was normalized by HAART. Plasma concentrations of Gal-9 were higher in HIV-1-infected individuals than in healthy individuals. Interestingly, Gal-9 expression in immune cells was significantly elevated in early infection, with monocytes and dendritic cells displaying the highest expression levels, which correlated with HIV-1 viral loads. In vitro, Gal-9 triggered Tim-3 downregulation on NK cells as well as NK cell activation. Our data suggest that high expression levels of Gal-9 during early HIV-1 infection can lead to enhanced NK cell activity, possibly allowing for improved early control of HIV-1. In contrast, persistent Gal-9 production might impair Tim-3 activity and contribute to NK cell dysfunction in chronic HIV-1 infection.
    Retrovirology 07/2013; 10(1):74. · 5.66 Impact Factor
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    ABSTRACT: Background. Clinical studies have shown faster disease progression and stronger immune activation in HIV-1-infected females as compared to males for the same level of HIV-1 replication. This study assesses whether the elevated levels of HIV-1-induced IFN-α production observed in females were associated with higher interferon-stimulated gene (ISG) expression levels in T-cells, and hence suggesting type-I-IFN as a mechanism for the higher HIV-1-associated immune activation observed.Methods. T-cell and dendritic cell populations were isolated from treatment-naïve chronically HIV-1-infected individuals enrolled in ACTG 384 by fluorescence activated cell sorting. The expression of 98 genes involved in toll-like receptor and type-I-IFN signaling pathways were quantified using Nanostring technology.Results. Several ISGs were significantly correlated with HIV-1 viral load and/or CD4(+) T-cell count. Higher expression levels of a subset of these ISGs were observed in cells derived from females as compared to males after adjusting for viral load, and were correlated to higher levels of T-cell activation.Conclusion. These data show that higher IFN-α production is associated with higher ex vivo expression of several ISGs in females. This might contribute to higher levels of immune activation, and the observed faster HIV-1 disease progression in females for a given level of viral replication.
    The Journal of Infectious Diseases 06/2013; · 5.85 Impact Factor
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    ABSTRACT: Innate immune activation was a strong predictor of HIV acquisition in women at risk for HIV in CAPRISA004. Identifying the cause/s of activation could enable targeted prevention interventions. In this study, plasma concentrations of lipopolysaccharide, soluble CD14 and intestinal fatty-acid binding protein did not differ between subjects who did or did not subsequently acquire HIV, nor were these levels correlated with plasma cytokines or natural killer cell activation. There was no difference between HIV-acquirers and non-acquirers in the chemokine and cytokine responses of peripheral blood mononuclear cells stimulated with TLR2, 4 or 7/8 agonists. Further studies are required.
    Journal of acquired immune deficiency syndromes 03/2013;
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    ABSTRACT: Innate immune activation was a strong predictor of HIV acquisition in women at risk for HIV in CAPRISA004. Identifying the cause/s of activation could enable targeted prevention interventions. In this study, plasma concentrations of lipopolysaccharide, soluble CD14 and intestinal fatty-acid binding protein did not differ between subjects who did or did not subsequently acquire HIV, nor were these levels correlated with plasma cytokines or natural killer cell activation. There was no difference between HIV-acquirers and non-acquirers in the chemokine and cytokine responses of peripheral blood mononuclear cells stimulated with TLR2, 4 or 7/8 agonists. Further studies are required.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2013; · 4.65 Impact Factor
  • Stephanie Jost, Marcus Altfeld
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    ABSTRACT: Natural killer (NK) cells are effector cells of the innate immune system and are important in the control of viral infection. Their relevance is reflected by the multiple mechanisms evolved by viruses to evade NK cell-mediated immune responses. Over recent years, our understanding of the interplay between NK cell immunity and viral pathogenesis has improved significantly. Here, we review the role of NK cells in the control of four important viral infections in humans: cytomegalovirus, influenza virus, HIV-1, and hepatitis C virus. Expected final online publication date for the Annual Review of Immunology Volume 31 is March 19, 2013. Please see for revised estimates.
    Annual Review of Immunology 01/2013; · 36.56 Impact Factor
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    ABSTRACT: Recent reports suggest that Natural Killer (NK) cells may modulate pathogenesis of primary HIV-1 infection. However, HIV dysregulates NK-cell responses. We dissected this bi-directional relationship to understand how HIV impacts NK-cell responses during primary HIV-1 infection. Paired samples from 41 high-risk, initially HIV-uninfected CAPRISA004 participants were analysed prior to HIV acquisition, and during viraemic primary HIV-1 infection. At the time of sampling post-infection five women were seronegative, 11 women were serodiscordant, and 25 women were seropositive by HIV-1 rapid immunoassay. Flow cytometry was used to measure NK and T-cell activation, NK-cell receptor expression, cytotoxic and cytokine-secretory functions, and trafficking marker expression (CCR7, α(4)β(7)). Non-parametric statistical tests were used. Both NK cells and T-cells were significantly activated following HIV acquisition (p = 0.03 and p<0.0001, respectively), but correlation between NK-cell and T-cell activation was uncoupled following infection (pre-infection r = 0.68;p<0.0001; post-infection, during primary infection r = 0.074;p = 0.09). Nonetheless, during primary infection NK-cell and T-cell activation correlated with HIV viral load (r = 0.32'p = 0.04 and r = 0.35;p = 0.02, respectively). The frequency of Killer Immunoglobulin-like Receptor-expressing (KIR(pos)) NK cells increased following HIV acquisition (p = 0.006), and KIR(pos) NK cells were less activated than KIR(neg) NK cells amongst individuals sampled while seronegative or serodiscordant (p = 0.001;p<0.0001 respectively). During HIV-1 infection, cytotoxic NK cell responses evaluated after IL-2 stimulation alone, or after co-culture with 721 cells, were impaired (p = 0.006 and p = 0.002, respectively). However, NK-cell IFN-y secretory function was not significantly altered. The frequency of CCR7+ NK cells was elevated during primary infection, particularly at early time-points (p<0.0001). Analyses of immune cells before and after HIV infection revealed an increase in both NK-cell activation and KIR expression, but reduced cytotoxicity during acute infection. The increase in frequency of NK cells able to traffic to lymph nodes following HIV infection suggests that these cells may play a role in events in secondary lymphoid tissue.
    PLoS ONE 01/2013; 8(1):e53251. · 3.53 Impact Factor

Publication Stats

12k Citations
1,737.54 Total Impact Points


  • 2014
    • Heinrich Pette Institute – Leibniz Institute for Experimental Virology
      Hamburg, Hamburg, Germany
  • 2009–2014
    • Ragon Institute of MGH, MIT and Harvard
      Charlestown, Maryland, United States
  • 2001–2013
    • University of KwaZulu-Natal
      • Centre for the AIDS Programme of Research in South Africa (CAPRISA)
      Port Natal, KwaZulu-Natal, South Africa
    • Institut de recherches cliniques de Montréal
      Montréal, Quebec, Canada
  • 2000–2013
    • Harvard Medical School
      • Division of AIDS
      Boston, Massachusetts, United States
    • Harvard University
      • Center for AIDS Research
      Cambridge, MA, United States
  • 2012
    • Massachusetts Institute of Technology
      Cambridge, Massachusetts, United States
    • Broad Institute of MIT and Harvard
      Cambridge, Massachusetts, United States
  • 2011
    • Seattle BioMed
      Seattle, Washington, United States
  • 2001–2011
    • University of Oxford
      • Department of Paediatrics
      Oxford, England, United Kingdom
  • 2000–2011
    • Massachusetts General Hospital
      • Division of Infectious Diseases
      Boston, MA, United States
  • 2010
    • National Institute of Allergy and Infectious Diseases
      Maryland, United States
    • Simon Fraser University
      • Department of Molecular Biology and Biochemistry
      Burnaby, British Columbia, Canada
    • The University of Tokyo
      Edo, Tōkyō, Japan
  • 2008
    • Fourth Military Medical University
      • Department of Infectious Diseases
      Xi’an, Liaoning, China
  • 2007
    • Centre for Eye Research Australia
      Melbourne, Victoria, Australia
  • 2004–2007
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
  • 2006
    • University of Oklahoma
      Norman, Oklahoma, United States
    • Asociacion Civil Impacta Salud y Educacion
      Λίμα, Provincia de Lima, Peru
  • 2005
    • Royal Perth Hospital
      Perth City, Western Australia, Australia
  • 1998–1999
    • University of Bonn
      • Medizinische Klinik und Poliklinik I
      Bonn, North Rhine-Westphalia, Germany