Biology subjects

Melo, J.

Publications and source records attributed to Melo, J..

4 recordsLinked to original sources

bioRxiv2026

Discovery of two potential new species and two novel bat-coronavirus subgenera (Phyllacovirus and Phyllobecovirus) in the Neotropics

Bats are major natural reservoirs for coronaviruses, yet complete viral genomes from South America remain scarce, limiting evolutionary and taxonomic understanding. Here, we conducted metatranscriptomic sequencing of coronavirus-positive bat samples collected across two ecologically distinct Brazilian biomes: the Atlantic Forest and the semi-arid Caatinga. We recovered seven complete or near-complete genomes belonging to Alphacoronavirus and Betacoronavirus. Phylogenetic and comparative similarity analyses of conserved replicase domains (3CLpro, NiRAN, RdRp, ZBD, HEL1), following International Committee on Taxonomy of Viruses (ICTV) demarcation criteria, revealed significant viral diversity. Within Alphacoronavirus, two genomes from Atlantic Forest phyllostomid bats (Artibeus lituratus and Carollia perspicillata) formed a deeply divergent sister lineage to Amalacovirus, exhibiting a mean amino acid similarity of 76.7% with the reference genome. Within Betacoronavirus, one genome from a Caatinga phyllostomid bat (Artibeus planirostris) clustered within the recently described Ambecovirus clade, displaying 75.9% mean amino acid similarity with mormoopid-associated reference sequences. Based on these divergence levels and non-recombinant genomic architectures, we propose two novel candidate subgenera, Phyllacovirus and Phyllobecovirus, alongside potential novel viral species. Furthermore, our findings demonstrate strong host-associated structuring and biogeographical partitioning of viral lineages across Neotropical biomes. Overall, this study expands the genomic landscape of South American bat coronaviruses and underscores the importance of continuous genomic surveillance at human-wildlife interfaces.

genomics↗

bioRxiv2026

Not so cold after all: tumor infiltrating CD8+ T cells in EBV-positive Burkitt lymphoma are quiescent, not exhausted

Abstract / SummarySurvival outcomes for pediatric Burkitt lymphoma (BL) substantially vary depending on geography (50-90%), which also serves as a proxy for the prevalence of Epstein-Barr virus (EBV) within the tumors. Although BL is considered an immunologically "cold" tumor with few tumor-infiltrating lymphocytes (TILs), their functional status has not been fully evaluated, especially for EBV-positive disease. Here, we characterize the exhaustion and activation profiles of T cells in the tumor microenvironment (TME) of EBV-positive BL using orthogonal methods, single-cell gene expression analysis, spectral flow cytometry, and immuno-histochemistry staining (IHC). We found that CD8+ TILs displayed a mosaic of immune inhibitory gene expression encoding, PD1, TIGIT, LAG3 and HAVCR2/TIM3. IHC validated the expression of PD1 and TIGIT on CD8+ TILs, as well as their respective ligands, PDL-1, PVR, and Nectin-2 on malignant B cells. Despite exhaustion-associated signatures, CD8+ TILs retain cytotoxic potential, expressing granules (i.e. Granzyme A, Perforin) and cytokines (i.e. IFN{gamma}) and demonstrate an increased uptake of metabolites such as glucose, arginine, and methionine. In peripheral blood, pediatric BL patients exhibited a significantly higher abundance of PD1+TIGIT+ CD8+ T cells compared to healthy children. Notably, these circulating T cells from BL patients express significantly lower levels of TOX, suggesting they are not irreversibly dysfunctional. Together, our results indicate that CD8+ T cells both in the TME and in circulation of children with BL are not terminally exhausted but remain poised for functional re-invigoration. These findings support the potential integration of immune checkpoint inhibitors into combination chemotherapeutic regimens to improve outcomes for these children. SignificanceEBV-positive BL tumors contain functional, metabolically active CD8+ T cells. Circulating PD1+TIGIT+CD8+ T cells found in BL patients blood are a biomarker for those in the tumor microenvironment.

immunology↗

bioRxiv2026

EBV Type 1 versus Type 2: A determinant of NK cell anti-tumor activity in Burkitt lymphoma

Terminally differentiated CD56negCD16pos NK cells have been described after chronic viral and malaria infections, and in children diagnosed with Burkitt lymphoma (BL). Despite CD56neg NK cells appearing to be poor at direct cytotoxicity, they express high levels of cytotoxic granules (i.e. granzymes, perforin), activation markers, and Fc-{gamma} receptors (CD32 and CD16) that are typically engaged in antibody-dependent cell cytotoxicity (ADCC). In addition, the abundance of CD56neg NK cells strongly correlates with IgG1 and IgG3 plasma levels, which are essential subclasses for ADCC. To determine whether CD56neg NK cells have superior ADCC capacity relative to CD56dim NK cells, we performed ADCC assays using effector cells from pediatric cancer patients and healthy children from malaria endemic regions of Kenya, targeting in vitro rituximab-treated commercial and newly established BL cell lines. We found that CD56neg NK cells were indeed capable of in vitro ADCC, showing a significant increase of CD107a-mediated degranulation in the presence of rituximab; however, they were not as efficient as CD56dim NK cells. Moreover, we found that the ADCC magnitude was significantly lower against EBV-Type 2 (EBV-T2) BL lines compared to EBV-Type 1 (EBV-T1). EBV-T2 tumor cell lines expressed significantly more lytic viral proteins than EBV-T1, making them more sensitive to direct cytotoxicity. Results from this study highlight the importance of assessing inter-patient variation in NK cell profiles in conjunction with ADCC sensitivity and EBV type within tumor cells when evaluating clinical outcomes for NK-mediated immunotherapies. SignificanceEBV type dictates NK cytotoxicity: EBV-T1 BL cells require rituximab for NK killing, while EBV-T2 BL cells are eliminated without antibody assistance, highlighting target-specific immune response to EBV-associated cancers.

immunology↗

bioRxiv2025

Anellovirus protein coded by ORF2/3 recruits host cell replication andhomologous recombination machinery during replication

Anelloviridae is a family of single-stranded DNA viruses that are thought to be non-pathogenic and commensal. Despite their ubiquitous presence in human populations, little is known about the anellovirus mechanism of replication in host cells. We identified the protein coded by ORF2/3 as necessary and sufficient to initiate replication from the minimal origin of replication for viruses of both the Beta- and Alphatorquevirus genera. Supporting this observation, we identified components of the polymerase alpha and BTR complexes as interacting with the viral replication initiation protein (Rip) during DNA replication, suggesting a recombination-dependent mechanism of replication that uses host cell machinery to mediate dissolution of replication intermediates. Furthermore, we mapped a 92-bp minimal origin of replication sequence for the Betatorquevirus genus comprised of an AT-rich stretch and a portion of the GC-rich region. Altogether, this study provides a first insight into the mechanism by which anelloviruses manipulate host cell machinery to facilitate viral genome replication and represents a significant step forward in understanding the complex processes underlying anellovirus replication and persistent infection of these important commensal viruses.

molecular biology↗