Although generally curable with intensive chemotherapy in resource-rich settings, Burkitt lymphoma (BL) remains a deadly disease in older patients and in sub-Saharan Africa. Epstein-Barr virus (EBV) positivity is a feature in more than 90% of cases in malaria-endemic regions, and up to 30% elsewhere. However, the molecular features of BL have not been comprehensively evaluated when taking into account tumor EBV status or geographic origin. Through an integrative analysis of whole-genome and transcriptome data, we show a striking genome-wide increase in aberrant somatic hypermutation in EBV-positive tumors, supporting a link between EBV and activation-induced cytidine deaminase (AICDA) activity. In addition to identifying novel candidate BL genes such as SIN3A, USP7, and CHD8, we demonstrate that EBV-positive tumors had significantly fewer driver mutations, especially among genes with roles in apoptosis. We also found immunoglobulin variable region genes that were disproportionally used to encode clonal B-cell receptors (BCRs) in the tumors. These include IGHV4-34, known to produce autoreactive antibodies, and IGKV3-20, a feature described in other B-cell malignancies but not yet in BL. Our results suggest that tumor EBV status defines a specific BL phenotype irrespective of geographic origin, with particular molecular properties and distinct pathogenic mechanisms. The novel mutation patterns identified here imply rational use of DNA-damaging chemotherapy in some patients with BL and targeted agents such as the CDK4/6 inhibitor palbociclib in others, whereas the importance of BCR signaling in BL strengthens the potential benefit of inhibitors for PI3K, Syk, and Src family kinases among these patients.

IL-17 is proinflammatory cytokine secreted by a unique CD4+ T (Th 17 ) cell subset and proposed to play a role in host defense. We hypothesized that Th 17 cells are lost in HIV-1 infection. HIV-1-infected children with plasma viremia below 50 copies/ml had IL-17 production, whereas those with detectable viremia had minimal secretion. These results imply viral-mediated destruction or impairment of Th 17 cells and argue for complete suppression of viremia for reconstitution of Th 17 cells.IL-17 is a proinflammatory cytokine [1], unique in that it is produced by a distinct subset of human CD4+ (Th 17 ) cells [2]. Recent studies [3][4][5][6][7][8][9] highlight the influence of IL-17 as a mediator of tissue inflammation in several autoimmune disorders and host defense. IL-17 may have a direct role in Candida or Mycobacterial infections, and a loss of Th 17 cells could potentially lead to vulnerability to opportunistic infections [10][11][12][13]. In this study, we assessed the impact of HIV-1 infection on Th 17 cells in a cohort of HIV-1-infected children [14]. First, we stimulated peripheral blood mononuclear cells (PBMCs) from healthy subjects with various monoclonal antibodies (mAb) and mitogenic stimuli for detection of IL-17 production in vitro. We observed that stimulation with anti-CD3/anti-CD28 mAbs induced IL-17 secretion, primarily by CD4+ T cells (data not shown). In response to anti-CD3/anti-CD28 stimulation, the majority of the Th 17 cells did not coexpress IFN-γ. In contrast, stimulation with phorbol myristate acetate/ionomycin induced IL-17 secretion from both CD4+ and CD8+ T cells, as well as dual secreting IL-17/IFN-γ T cell subsets (data not shown). These results suggest that anti-CD3/anti-CD28 stimulation is an effective method to We next tested for the frequency of Th 17 cells in PBMCs using an anti-CD3/anti-CD28 stimulation IL-17 enzyme-linked immunosorbent spot assay in 12 HIV-1-infected children with differing levels of plasma viremia and compared this to a group of HIV-1-uninfected subjects who served as controls. The median number of IL-17-specific spot forming units (SFU) in healthy pediatric and adult subjects was 300 SFU/10 6 (range: 85-970 SFU/10 6 ; n = 12) and 760 SFU/10 6 (range: 110-1370 SFU/10 6 ; n = 7), respectively (Fig. 1a). A marked reduction in Th 17 cells was observed in the HIV-1-infected children (median: 62 SFU/10 6 ; range: 10-270 SFU/10 6 ; n = 12). Strikingly, the infected children with HIV-1 plasma viral loads exceeding 50 copies/ml had minimal numbers of Th 17 cells (median: 35 SFU/10 6 ; range: 10-95 SFU/10 6 ; n = 7), whereas those with suppressed viral loads had higher levels of Th 17 cells (median: 170 SFU/10 6 ; range: 75-270 SFU/10 6 ; n = 5). Interestingly, all groups had robust IFN-γ secretion (Fig. 1b). Flow cytometry assessment confirmed that CD4+ T cells were the primary source of IL-17 following anti-CD3/anti-CD28 mAb stimulation (data not shown). We carried out a univariate logistic regression analysis to test for an association between HIV-1 plasm...

Pulmonary toxoplasmosis is rare in immunocompetent subjects. Here, we describe a 41-year-old previously healthy male patient who presented to the emergency department of a hospital with a life-threatening case of pneumonia due to Toxoplasma gondii infection, which responded to specific therapy. Clinical and image-based findings overlap with those for atypical pneumonias, and toxoplasmosis should be considered in the differential diagnosis--especially if immunoglobulin M-specific antibodies are detected.

Background : SARS-CoV-2 quickly spreads in the worldwide population, imposing social restrictions to control the infection, being the massive testing another essential strategy to break the chain of transmission. Aim : To compare the performance of at-home self-collected samples – saliva and combined nasal-oropharyngeal swabs (NOP) – for SARS-CoV-2 detection in a telemedicine platform for COVID-19 surveillance. Material and methods : We analyzed 201 patients who met the criteria of suspected COVID-19. NOP sampling was combined (nostrils and oropharynx) and saliva collected using a cotton pad device. Detection of SARS-COV-2 was performed by using the Altona RealStar® SARS-CoV-2 RT-PCR Kit 1.0. Results: There was an overall significant agreement (κ coefficient value of 0.58) between saliva and NOP. Considering results in either sample, 70 patients positive for SARS-CoV-2 were identified, with 52/70 being positive in NOP and 55/70 in saliva. This corresponds to sensitivities of 74.2% (95% CI; 63.7% to 83.1%) for NOP and 78.6% (95% CI; 67.6% to 86.6%) for saliva. Conclusion : Our data show the feasibility of using at-home self-collected samples (especially saliva), as an adequate alternative for SARS-CoV-2 detection. This new approach of testing can be useful to develop strategies for COVID-19 surveillance and for guiding public health decisions.

In diseases where epigenetic mechanisms are changed, such as cancer, many genes show altered gene expression and inhibited genes become activated. Human endogenous retrovirus type K (HERV-K) expression is usually inhibited in normal cells from healthy adults. In tumor cells, however, HERV-K mRNA expression has been frequently documented to increase. Importantly, HERV-K-derived proteins can act as tumor-specific antigens, a class of neoantigens, and induce immune responses in different types of cancer. In this review, we describe the function of the HERV-K HML-2 subtype in carcinogenesis as biomarkers, and their potential as targets for cancer immunotherapy.

No abstract

HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develop HAM/TSP. The cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. Furthermore, HTLV-1-infected individuals have an increase incidence of Mycobacterium tuberculosis (Mtb) infection, suggesting that immunological defect are associated with HTLV-1 infection. Evidence suggests an important role for Mucosal-associated invariant T (MAIT) cells in the early control of Mtb infection. Chronic viral infections like HIV and HCV have been associated with decreased frequency and functionality of MAIT cells. We hypothesized that HTLV-1 infection is associated with similar perturbations in MAIT cells. We investigated MAIT cell frequency, phenotype, and function by flow cytometry in a cohort of 10 asymptomatic and 10 HAM/TSP HTLV-1 infected patients. We found that MAIT cells from HTLV-1-infected subjects were reduced and showed high co-expression of the activation markers CD38 and HLA-DR but normal levels of CCR6 and CD127. MAIT cells had a lower expression of the transcription factor PLZF in HAM/TSP patients. Unlike Tax-specific CD8+T cells, which are hyperfunctional, MAIT cells from HTLV-1-infected subjects had a poor IFNγ response following antigen stimulation. MAIT cell perturbations in HTLV-1 infection were not associated with HTLV-1 proviral load and MAIT cells were not infected by HTLV-1 in vivo. Rather, MAIT cells loss was associated with immune activation. Overall, our results do not support a role for MAIT cells in HAM/TSP pathogenesis but reduced numbers of MAIT cells, together with their poor functionality, could contribute to the increased susceptibility of HTLV-1-infected individuals to other infectious agents.

HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develops HAM/TSP. CD4+ T cells are the main target of infection and play a pivotal role in regulating immunity to HTLV and are hypothesized to participate in the pathogenesis of HAM/TSP. The CD39 ectonucleotidase receptor is expressed on CD4+ T cells and based on co-expression with CD25, marks T cells with distinct regulatory (CD39+CD25+) and effector (CD39+CD25−) function. Here, we investigated the expression of CD39 on CD4+ T cells from a cohort of HAM/TSP patients, HTLV-1 asymptomatic carriers (AC), and matched uninfected controls. The frequency of CD39+ CD4+ T cells was increased in HTLV-1 infected patients, regardless of clinical status. More importantly, the proportion of the immunostimulatory CD39+CD25− CD4+ T-cell subset was significantly elevated in HAM/TSP patients as compared to AC and phenotypically had lower levels of the immunoinhibitory receptor, PD-1. We saw no difference in the frequency of CD39+CD25+ regulatory (Treg) cells between AC and HAM/TSP patients. However, these cells transition from being anergic to displaying a polyfunctional cytokine response following HTLV-1 infection. CD39−CD25+ T cell subsets predominantly secreted the inflammatory cytokine IL-17. We found that HAM/TSP patients had significantly fewer numbers of IL-17 secreting CD4+ T cells compared to uninfected controls. Taken together, we show that the expression of CD39 is upregulated on CD4+ T cells HAM/TSP patients. This upregulation may play a role in the development of the proinflammatory milieu through pathways both distinct and separate among the different CD39 T cell subsets. CD39 upregulation may therefore serve as a surrogate diagnostic marker of progression and could potentially be a target for interventions to reduce the development of HAM/TSP.