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.

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.

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.