Biology subjects

Lee, W.-Y. J.

Publications and source records attributed to Lee, W.-Y. J..

4 recordsLinked to original sources

bioRxiv2026

HIV-1 Vpr counteracts TASOR restriction to promote infection prior to integration

HIV-1 is challenged by many intrinsic antiviral factors including APOBEC3G, Tetherin/BST-2 and SERINC5 which are overcome by viral accessory proteins Vif, Vpu and Nef respectively. HIV-1 Vpr has multiple proposed cellular targets including REAF, previously shown by us to restrict early after virus entry, but its function is incompletely understood. TASOR is a component of HuSH, an epigenetic silencing complex which inhibits expression of HIV-1 and is overcome by HIV-2/SIV Vpx. We report that TASOR, in addition to silencing integrated provirus, inhibits viral replication prior to integration during reverse transcription. TASOR impairs viral replication in primary macrophages and restriction of a primary isolate is also shown. The restriction to replication is overcome by HIV-1 Vpr which induces TASOR degradation concomitant with reverse transcription. Using Vpr mutants Q65R and F34I we show that interaction with the CRL4-DCAF1 E3 ligase and nuclear localisation are required for Vpr to mitigate TASOR. The pre and post integration mechanism of Vpr mediated TASOR mitigation is genetically segregated using cell cycle Vpr mutant R80A. TASOR depletion induces cells to accumulate in G2/M and arrested cells are more susceptible to HIV-1. Understanding the mechanistic details of pathogen-host interactions is critical for the design of effective anti-HIV/AIDS therapeutics.

immunology↗

bioRxiv2025

Single-cell mass cytometry maps the evolution of immune cell signatures predictive of acute graft-versus-host disease

Allogeneic haematopoietic stem-cell transplantation (AHST) can cure patients with many diseases, but harmful acute graft-versus-host disease (aGvHD) remains a challenge. Many immune cells are implicated in the pathogenesis and control of alloreactive T-cell responses causing aGvHD, but the functionally dominant cells at different times remain unknown. Using mass cytometry to simultaneously assess alloreactive and immunoregulatory cell populations after AHST, we identified a robust early immune signature predictive of aGvHD rich in CD4 effector memory T-cells and deficient in functionally allosuppressive NK cells. Additionally, network analysis identified a heterogeneous immunoregulatory cell group (IRCG) that more accurately predicted aGVHD than any individual cell populations or established serum biomarkers. Immune signatures preceding aGvHD evolved over time, with qualitative and quantitative changes in both the alloreactive T-cell compartment and the constituent components of the IRCG. In mapping how alloreactive and immunoregulatory cell populations evolve temporally, we provide mechanistic insight into dynamic control of alloreactivity supporting development of time-sensitive targeted strategies to reduce aGvHD. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=184 HEIGHT=200 SRC="FIGDIR/small/640331v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@12bb519org.highwire.dtl.DTLVardef@7e9dbcorg.highwire.dtl.DTLVardef@a5b041org.highwire.dtl.DTLVardef@1d69a82_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2020

Deep mining of early antibody response in COVID-19 patients yields potent neutralisers and reveals high level of convergence

Passive immunisation using monoclonal antibodies will play a vital role in the fight against COVID-19. Until now, the majority of anti-SARS-CoV-2 antibody discovery efforts have relied on screening B cells of patients in the convalescent phase. Here, we describe deep-mining of the antibody repertoires of hospitalised COVID-19 patients using a combination of phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralising antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded potent neutralising antibodies with distinct mechanisms of action, including the identification of a novel non-ACE2 receptor blocking antibody that is not expected to be affected by any of the major viral variants reported. The study highlighted the presence of potent neutralising antibodies with near germline sequences within both the IgG and IgM pools at early stages of infection. Furthermore, we highlight a highly convergent antibody response with the same sequences occurring both within this study group and also within the responses described in previously published anti-SARS-CoV-2 studies.

immunology↗

bioRxiv2020

Deep sequencing of B cell receptor repertoires from COVID-19 patients reveals strong convergent immune signatures

Deep sequencing of B cell receptor (BCR) heavy chains from a cohort of 19 COVID-19 patients from the UK reveals a stereotypical naive immune response to SARS-CoV-2 which is consistent across patients and may be a positive indicator of disease outcome. Clonal expansion of the B cell memory response is also observed and may be the result of memory bystander effects. There was a strong convergent sequence signature across patients, and we identified 777 clonotypes convergent between at least four of the COVID-19 patients, but not present in healthy controls. A subset of the convergent clonotypes were homologous to known SARS and SARS-CoV-2 spike protein neutralising antibodies. Convergence was also demonstrated across wide geographies by comparison of data sets between patients from UK, USA and China, further validating the disease association and consistency of the stereotypical immune response even at the sequence level. These convergent clonotypes provide a resource to identify potential therapeutic and prophylactic antibodies and demonstrate the potential of BCR profiling as a tool to help understand and predict positive patient responses.

immunology↗