Biology subjects

Pham, T. N.

Publications and source records attributed to Pham, T. N..

10 recordsLinked to original sources

bioRxiv2026

HIV-1 Vpu complements HLA-A downregulation by Nef and impairs TCR-mediated recognition of HIV-infected cells through distinct mechanisms

Many viruses, including HIV-1, target the human leukocyte antigen (HLA) class I molecules HLA-A, HLA-B, and HLA-C to evade immune surveillance. HIV-1 Nef selectively downregulates HLA-A and HLA-B, whereas Vpu variants from primary strains reduce cell-surface HLA-C expression. Whether HIV-1 also uses Vpu to target other HLA molecules has remained unclear. Here, we show that Vpu from primary strains reduces HLA-A, including the globally prevalent HLA-A2, on infected cells. Although Nef is the principal modulator of these molecules, Vpu acts independently of Nef and impairs TCR-mediated recognition of infected cells in co-culture systems. However, the reduction in TCR signaling is also dependent on the presence of BST2/tetherin, a restriction factor that retains nascent virions and targets them for degradation. HLA-A2-restricted, HIV-specific CTL responses were lowest when both Nef and Vpu were present. Vpu variants from chronic and transmitted/founder strains, but not from the prototypical recombinant strain NL4.3, were sufficient to reduce cell-surface HLA-A2, although activity varied widely among variants and appears to have arisen independently in different hosts. Coimmunoprecipitation and immunofluorescence analyses showed that Vpu interacts with HLA-A2 and redirects it to a perinuclear compartment which is probably the trans-Golgi network through a mechanism governed by the Vpu N-terminus/transmembrane domain. Overall, our findings reveal a previously unrecognized function of Vpu and show how HIV-1 uses Nef and Vpu to limit HLA-A-mediated viral antigen presentation and promote immune evasion.

immunology↗

bioRxiv2026

Conservation value of secondary and plantation forests for fruit-feeding butterflies in northern Vietnam

1. Assessing the conservation value of secondary forests and reforestation is important for conservation planning. Butterflies are widely used as indicators, and fruit-feeding butterflies are often used in biodiversity assessments in tropical landscapes. 2. We examined fruit-feeding butterfly diversity, abundance, and community composition across a primary forest, a secondary forest, and a plantation forest in northern Vietnam. We sampled butterflies nearly monthly during one year using baited traps. 3. Primary and secondary forest supported higher species richness than plantation forest. Moreover, while secondary forest had mainly a subset of species found in primary forest, the plantation forest had a distinct butterfly fauna. 4. Butterfly abundance and community composition varied across months, without showing a clear seasonal pattern. 5. Our results suggest that secondary and plantation forests do not fully replace primary forests, but they contribute meaningfully to butterfly conservation in human-modified tropical landscapes.

ecology↗

bioRxiv2026

Genome Report: Long read, high-coverage reference genomes of the Nymphalid butterflies Catonephele acontius and C. numilia (Nymphalidae: Biblidinae)

Withdrawal StatementThe authors have withdrawn this manuscript because in February 2026, the authors found that the Catonephele numilia specimen was misidentified and was in fact also Catonephele acontius. Thus, the data in the article describing the Catonephele numilia genome is invalid, as it in fact describes a second Catonephele acontius genome. This data invalidation has resulted in a loss of confidence in the results and conclusions reported in the article as far as they apply to Catonephele numilia. The data describing Catonephele acontius is not affected and remains valid. The authors are, therefore, retracting this article. All authors agree with the retraction. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

genomics↗

bioRxiv2025

A high-quality draft genome assembly of the Neotropical butterfly, Batesia hypochlora (Nymphalidae: Biblidinae)

We report a long-read high-coverage reference genome assembly of the Neotropical butterfly, Batesia hypochlora (Nymphalidae: Biblidinae). This represents the first reference genome in the Biblidinae subfamily, a clade subject to ongoing studies on seasonal and climate adaptation in the Amazon. We assembled the genome from PacBio HiFi long reads (66X coverage), polished it with Illumina short reads (15X coverage), and annotated it using PacBio IsoSeq RNA data. We observed 15 chromosome-sized scaffolds varying in length from 13.2 Mbp to 37.6 Mbp (median 24.3 Mbp), combining a total genome size of 395.788 Mbp. This assembly is highly contiguous (contig N50 of 25.14 Mbp) and complete (BUSCO completeness score of 98.6% and 0.2% duplication rate). Repeat annotation revealed that the genome consists of about one-third transposable elements. Gene prediction using RNAseq evidence uncovered 19,395 genes, of which 17,400 were assigned to 2,883 orthogroups when including genomes of the fruitfly, silk moth, and three other Nymphalid butterfly species. The high sequencing depth also allowed us to assemble the genomes of the mitochondria and the common endosymbiotic bacterium Wolbachia. The mitochondrial genome was fully assembled (15,540 bp in size) with all expected genes annotated. The Wolbachia genome was fragmented, and we determined that it belongs to the B-supergroup. The high-quality assembly of B. hypochlora can represent the subfamily in further comparative analysis of evolution and provide a key resource for ongoing work to explore reproductive biology and adaptations to seasonality in Amazonian butterflies.

genomics↗

bioRxiv2025

Humanized Bone Marrow-Liver-Thymus Mice for Studying HIV-1 Persistence in Liver and Lung CD4+ T and Myeloid Cell Subsets during Antiretroviral Therapy

BackgroundWhile the role of CD4+ T-cells in HIV-1 reservoir persistence during antiretroviral therapy (ART) is well-established, studies on tissue-resident macrophages (M{Phi}) in people with HIV-1 (PWH) are restricted by difficulties in accessing deep tissue samples. Investigations in myeloid-only humanized mouse models demonstrated the contribution of M{Phi} to viral rebound upon ART interruption. Two distinct M{Phi} subsets exist in mice and humans: one of embryonic origin and self-renewal capacity generating long-lived tissue-resident M{Phi} (LL-TRM), and another one of short-lived M{Phi} (SL-M{Phi}), constantly replenished by bone marrow monocytes. The relative contribution of LL-TRM versus SL-M{Phi} to tissue HIV-1 reservoir persistence during ART remains understudied. Here, we used a humanized BM-liver-thymus (hu-BLT) mouse model to quantify integrative HIV-1 infection in liver/lung M{Phi} versus CD4+ T-cells before/after ART and document their expression of LL-TRM/SL-M{Phi} markers. ResultsLung/liver immune cells were extracted from ART-naive (ART-) and ART-treated (ART+) HIV-infected (HIV+) hu-BLT mice, as well as HIV-uninfected mice (HIV-). M{Phi} were identified as cells expressing the myeloid markers CD33/HLA-DR and/or CD68 and flow-cytometry sorted based on their differential expression of CD14 and/or CCR2. Matched CD3+CD4+ T-cells were sorted in parallel and used as controls. HIV-DNA integration was measured by nested real-time PCR. In contrast to CD4+ T-cells that carried the highest levels of proviral HIV-DNA before and after ART, integrative infection in liver/lung M{Phi} was detected before ART, but was drastically reduced in HIV+ART+ hu-BLT mice, regardless of CD14 or CCR2 expression on M{Phi}. Markers of LL-TRM (CD163/CX3CR1/Ki67/c-Kit) were expressed on a small fraction of liver but not lung M{Phi}, indicative of a deficient LL-TRM development in this hu-BLT model. ConclusionsTogether our results demonstrate that lung/liver M{Phi} in hu-BLT mice support integrative HIV-1 infection in vivo, but their contribution to viral reservoir persistence during ART is minor when compared to CD4+ T-cells. This is consistent with the deficient development of LL-TRM we observed in hu-BLT mice. However, HIV-1 permissive M{Phi} present in this model likely contribute to viral rebound upon ART interruption. Therefore, HIV-1 cure interventions that are tested in such preclinical models should consider targeting HIV-1 replication in both M{Phi} and CD4+ T-cells.

immunology↗

bioRxiv2024

Investigating the effects of protons versus x-rays on radiation-induced lymphopenia after brain irradiation

BackgroundConventional x-ray-based radiotherapy is a standard treatment for patients with brain tumors. However, is associated with systemic effects like lymphopenia that correlates with poor prognosis. Proton therapy has emerged as a new radiation strategy, given that the lower entry dose and absence of exit dose can be exploited to spare healthy brain tissues and reduce side-effects caused by systemic inflammation. We evaluated if brain irradiation with protons could spare circulating leukocytes along with other variables in rodent models. MethodsTumor-free C57BL/6 mice were irradiated with a total dose of 20Gy in 2.5Gy twice-daily sessions over four consecutive days with either x-rays or protons. Groups of mice were defined according to irradiation volume (whole-brain or hemisphere) and dose rate (1 or 2Gy/min). Blood was withdrawn at various time points and circulating lymphoid, with myeloid subpopulations analyzed using flow cytometry. Brain tissue histochemical analyses were performed late after irradiation. ResultsBlood sampling showed severe and acute radiation-induced lymphopenia after x-rays, with marked depletion of 50% CD4+ and CD8+, as well as B and NK cells. With protons, the decrease was 20% on average for whole-brain irradiations, suggesting a conservative effect on circulating lymphocytes. The data showed no effect in CD11b+ myeloid cells for both x-rays and protons. Histological analyses revealed a more intense expression level of CD68 and Iba1 immunostaining after x-ray irradiation. GFAP staining was well detected after both beams. ConclusionProton therapy for brain tumors differs from photon therapy in terms of its effects on circulating cells and tissues. Key pointsO_LIX-ray brain irradiation induced an acute severe lymphopenia, with a reduction of at least 50% lymphocytes. The whole-brain irradiation caused a more pronounced decrease in lymphocytes than hemisphere irradiation. Proton brain irradiation exhibited a conservative effect on circulating leukocytes. C_LIO_LIX-ray irradiation-induced lymphopenia is followed by a recovery of all lymphocyte subpopulations to control levels. However, this recovery is longer for CD3+ lymphocytes, and B and NK cells, depending on irradiation modalities. C_LIO_LILong-term brain tissue histochemical analyses demonstrated differences between the two beams, consisting of a macrophage/microglial activation seen mostly after x-rays while an astrocyte reaction was seen after brain exposure to the two beams. These differences may explain the disparities observed in leukocytes, thereby favoring a specific biological reaction between the brain and blood. C_LI Importance of the StudyOur study demonstrated that while whole-brain or hemispheric irradiation with x-rays resulted in lymphopenia, proton brain irradiation exhibited a conservative effect on circulating lymphocytes, which was paralleled by a less intense brain tissue reaction.

cell biology↗

bioRxiv2023

BET inhibition rescues ciliogenesis and ameliorates pancreatitis-driven phenotypic changes in mice with Par3 loss.

The apical-basal polarity of pancreatic acinar cells is essential for maintaining tissue architecture. However, the mechanisms by which polarity proteins regulate acinar pancreas tissue homeostasis are poorly understood. Here, we evaluate the role of Par3 in acinar pancreas injury and homeostasis. While Par3 loss in the mouse pancreas disrupts tight junctions, Par3 loss is dispensable for pancreatogenesis. However, with aging, Par3 loss results in low-grade inflammation, acinar degeneration, and pancreatic lipomatosis. Par3 loss also exacerbates pancreatitis-induced acinar cell loss, resulting in pronounced pancreatic lipomatosis and failure to regenerate. Moreover, Par3 loss in mice harboring mutant Kras causes extensive pancreatic intraepithelial neoplastic (PanIN) lesions and large pancreatic cysts. We also show that Par3 loss restricts injury-induced primary ciliogenesis. Significantly, targeting BET proteins enhances primary ciliogenesis during pancreatitis-induced injury and, in mice with Par3 loss, limits pancreatitis-induced acinar loss and facilitates acinar cell regeneration. Combined, this study demonstrates how Par3 restrains pancreatitis- and Kras-induced changes in the pancreas and identifies a potential role for BET inhibitors to attenuate pancreas injury and facilitate pancreas tissue regeneration.

pathology↗

bioRxiv2021

Implications of Spike-glycoprotein processing at S1/S2 by Furin, at S2' by Furin and/or TMPRSS2 and shedding of ACE2: cell-to-cell fusion, cell entry and infectivity of SARS-CoV-2

Disclaimer StatementThe author has withdrawn this manuscript due to a duplicate posting of manuscript number 423106. Therefore, the author does not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author (Nabil G. Seidah at seidahn@ircm.qc.ca.

biochemistry↗

bioRxiv2021

HIV-1 Vpu promotes phagocytosis of infected CD4+ T cells by macrophages through downregulation of CD47

Human immunodeficiency virus (HIV) remodels the cell surface of infected cells to facilitate viral dissemination and promote immune evasion. The membrane-associated Vpu accessory protein encoded by HIV-1 plays a key role in this process by altering cell surface levels of multiple host proteins. Using an unbiased quantitative plasma membrane profiling approach, we previously identified CD47 as a putative host target downregulated by Vpu. CD47 is a ubiquitously-expressed cell surface protein that interacts with the myeloid cell inhibitory receptor SIRP to deliver a "dont-eat-me" signal, thus protecting cells from phagocytosis. In this study, we investigate whether CD47 modulation by HIV-1 Vpu might promote the susceptibility of macrophages to viral infection via phagocytosis of infected CD4+ T cells. Indeed, we find that Vpu downregulates CD47 expression on infected CD4+ T cells leading to an enhanced capture and phagocytosis by macrophages. Interestingly, it is through this process that a CCR5-tropic transmitted/founder (T/F) virus, which otherwise poorly infects macrophages in its cell-free form, becomes infectious in macrophages. Importantly, we show that HIV-1-infected cells expressing a Vpu-resistant CD47 mutant are less prone to infect macrophages through phagocytosis. Mechanistically, Vpu forms a physical complex with CD47 through its transmembrane domain and targets the latter for lysosomal degradation. These results reveal a novel role of Vpu in modulating macrophage infection, which has important implications for HIV-1 transmission in early stages of infection and the establishment of viral reservoir. IMPORTANCEMacrophages play critical roles in HIV transmission, viral spread early in infection, and as a reservoir of virus. Selective capture and engulfment of HIV-1 infected T cells was shown to drive efficient macrophage infection suggesting that this mechanism represents an important mode of infection notably for weakly macrophage-tropic T/F viruses. In this study, we provide insight into the signals that regulate this process. We show that the HIV-1 accessory protein Vpu downregulates cell surface levels of CD47, a host protein that interacts with the inhibitory receptor SIRP to deliver a "dont-eat-me" signal to macrophages. This allows for enhanced capture and phagocytosis of infected T cells by macrophages, ultimately leading to their productive infection even with T/F virus. These findings provide new insights into the mechanisms governing the intercellular transmission of HIV-1 to macrophages with implications for the establishment of the macrophage reservoir and early HIV-1 dissemination in vivo.

microbiology↗

bioRxiv2021

Gα13 loss promotes tumor progression in the KPC transgenic mouse model of advanced pancreatic cancer

G13 transduces signals from G protein-coupled receptors. G13 is pro-tumorigenic in epithelial cancer cell lines, which contrasts with its tumor-suppressive function in transgenic mouse models of lymphomas. Here we show that while loss of G13 in pancreatic cell lines decreases tumor growth in vivo, G13 loss in the Kras-driven (KC) mouse model of pancreatic tumor initiation does not affect tumor development or survival. Instead, G13 loss in the Kras/Tp53 (KPC) transgenic mouse model of advanced pancreatic cancer promotes well-differentiated tumors with increased tumor burden and reduced survival. Mechanistically, G13 loss in the KPC mouse model enhances E-cadherin-mediated cell-cell junctions and mTOR signaling. Importantly, human pancreatic cancers with low G13 expression exhibit increased E-cadherin protein expression and mTOR signaling. This work establishes a context-dependent role of G13 in pancreatic tumorigenesis, demonstrating a tumor-suppressive role in transgenic mouse models of advanced pancreatic cancer.

cancer biology↗