A5100740375- HIV Research and Treatment
- Cell Image Analysis Techniques
- Immune Cell Function and Interaction
- Advanced Fluorescence Microscopy Techniques
- Rabies epidemiology and control
- Single-cell and spatial transcriptomics
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
- Retinal Development and Disorders
- Cytomegalovirus and herpesvirus research
- Virus-based gene therapy research
- Neuroscience and Neural Engineering
- Bacillus and Francisella bacterial research
- Photoreceptor and optogenetics research
- Venomous Animal Envenomation and Studies
- Autoimmune Neurological Disorders and Treatments
- Respiratory viral infections research
- T-cell and B-cell Immunology
- Chemokine receptors and signaling
- Bacteriophages and microbial interactions
- Access Control and Trust
- interferon and immune responses
- Adenosine and Purinergic Signaling
- Redox biology and oxidative stress
- Poxvirus research and outbreaks
McGovern Institute for Brain Research
2019-2024
Massachusetts Institute of Technology
2019-2024
First Affiliated Hospital of Anhui Medical University
2024
Anhui Medical University
2024
Second Hospital of Anhui Medical University
2024
Moscow Institute of Thermal Technology
2022-2024
Allen Institute
2023
Allen Institute for Brain Science
2023
Huashan Hospital
2022-2023
Fudan University
2000-2023
Construction of a complex virus may involve hierarchy assembly elements. Here, we report the structure whole human adenovirus virion at 3.6 angstroms resolution by cryo-electron microscopy (cryo-EM), revealing in situ atomic models three minor capsid proteins (IIIa, VIII, and IX), extensions (penton base hexon) major proteins, interactions within protein-protein networks. One network is mediated protein IIIa vertices, group-of-six (GOS) tiles--a penton its five surrounding hexons. Another...
Abstract Rabies-virus-based monosynaptic tracing is a widely used technique for mapping neural circuitry, but its cytotoxicity has confined it primarily to anatomical applications. Here we present second-generation system labeling direct inputs targeted neuronal populations with minimal toxicity, using double-deletion-mutant rabies viruses. Viral spread requires expression of both deleted viral genes in trans postsynaptic source cells. Suppressing this doxycycline following an initial period...
Background: Enfuvirtide (ENF) is the first of a novel class drugs that block HIV gp41-mediated viral fusion to host cells. Viruses with mutations at positions 36–38 in HIV-1 gp41 and/or reduced susceptibility ENF have been selected both vitro and vivo. Methods: An analysis baseline on-treatment virus samples from Phase II clinical trial patients treated as functional monotherapy for 28 days (TRI-003) or combination oral antiretrovirals ≥ 48 weeks (T20–205, T20–206 T20–208). Population...
Enfuvirtide (ENF), a novel human immunodeficiency virus type 1 (HIV-1) fusion inhibitor, has potent antiviral activity against HIV-1 both in vitro and vivo. Resistance to ENF observed after passaging was associated with changes three-amino-acid (aa) motif, GIV, at positions 36 38 of gp41. Patients ongoing viral replication while receiving during clinical trials acquired substitutions within gp41 aa 45 the first heptad repeat (HR-1) population-based plasma sequences proviral DNA from isolates...
Monosynaptically-restricted transsynaptic tracing using deletion-mutant rabies virus has become a widely used technique in neuroscience, allowing identification, imaging, and manipulation of neurons directly presynaptic to starting neuronal population. Its most common implementation is use Cre mouse lines combination with Cre-dependent "helper" adeno-associated viral vectors (AAVs) supply the required genes targeted population before subsequent injection first-generation (∆G) vector. Here we...
To obtain a comprehensive scenario of T cell profiles and synergistic immune responses, we performed single-cell RNA sequencing (scRNA-seq) on the peripheral cells 14 individuals with chronic human immunodeficiency virus 1 (HIV-1) infection, including nine treatment-naive (TP) eight antiretroviral therapy (ART) participants (of whom three were paired TP cases), compared results four healthy donors (HD). Through analyzing transcriptional CD4+ CD8+ cells, coupled assembled receptor sequences,...
Monosynaptic tracing using rabies virus is an important technique in neuroscience, allowing brain-wide labeling of neurons directly presynaptic to a targeted neuronal population. A 2017 article reported the development noncytotoxic version-a major advance-based on attenuating by addition destabilization domain C terminus viral protein. However, this modification did not appear hinder ability spread between neurons. We analyzed two viruses provided authors and show here that both were mutants...
Numerical and functional deficits in myeloid (mDC) plasmacytoid dendritic cell (pDC) subsets have been found both adult pediatric HIV-1 carriers. Whether these impaired DC can be restored after treatment with highly active antiretroviral therapy (HAART) is currently unknown, especially HIV-1-infected children. In this report, we characterized mDC pDC 18 children who received HAART compared them those 6 untreated 27 HIV-1-uninfected healthy Among treated HAART, 11 were to suppress replication...
Abstract There is growing interest in engineering nerve cells vitro to control architecture and connectivity of cultured neuronal networks or build with predictable computational function. Pattern technologies, such as micro-contact printing, have been developed design ordered networks. However, electrophysiological characteristics the single patterned neuron haven’t reported. Here, using polyolefine polymer (POP) stamps high resolution, was employed grow cortical neurons a designed...
Background. Whether varying CD8 counts influence on human immunodeficiency virus (HIV) reservoir and CD4 restoration in patients with ≥ 500 cells/μL after long-term antiretroviral therapy (ART) remains unknown. In this study, we analyzed relationships between levels viral decay or recovery immune restored ART. Methods. Chronic HIV-infected who received 5-year ART were grouped according to counts: <500 (Group1), 500-1000 (Group2) ≥1000 (Group3). recovery, decay, T-cells function their...
Nonspecific T-cell hyperactivation is the main driving force for human immunodeficiency virus (HIV)-1 disease progression, but reasons why excess immune response not properly shut off are poorly defined.Eighty-five HIV-1-infected individuals were enrolled to characterize B and T lymphocyte attenuator (BTLA) expression function. Infection blockade assays used dissect factors that influenced BTLA signaling in vitro.BTLA on overall CD4(+) CD8(+) cells was progressively decreased HIV-1...
Background: CXCR5+CD8+T cells have been demonstrated to play an important role in the control of chronic viral replication; however, relationship between cells, HIV disease progression, and PD-1 expression profile on during infection remain poorly understood. Methods: We enrolled a total 101 patients, including 62 typical progressors (TPs), 26 complete responders (CRs), 13 immune non-responders (INRs). Flow cytometric analysis, immunohistochemical staining, relative function (i.e., cytokine...
Mapping the connectivity of diverse neuronal types provides foundation for understanding structure and function neural circuits. High-throughput low-cost neuroanatomical techniques based on RNA barcode sequencing have potential to map circuits at cellular resolution a brain-wide scale, but existing Sindbis virus-based can only long-range projections using anterograde tracing approaches. Rabies virus complement approaches by enabling either retrograde labeling projection neurons or...
Rabies viral vectors have become important components of the systems neuroscience toolkit, allowing both direct retrograde targeting projection neurons and monosynaptic tracing inputs to defined postsynaptic populations, but rapid cytotoxicity first-generation (ΔG) limits their use short-term experiments. We recently introduced second-generation, double-deletion-mutant (ΔGL) rabies vectors, showing that they efficiently retrogradely infect express recombinases effectively with little no...
Enfuvirtide (ENF), the first human immunodeficiency virus type 1 (HIV-1) fusion inhibitor approved for clinical use, acts by binding to gp41 heptad repeat (HR1) and preventing its interaction with viral HR2 region. Treatment-emergent resistance ENF has been mapped residues within HR1, these mutations decrease susceptibility may reduce fitness pathogenesis, although mechanism effects is not clear. N43D, a common mutation, was found in vitro assays cause 5-50-fold antiviral activity. We...
The phenotype of peripheral neuropathy (PN) associated with glial fibrillary acidic protein-immunoglobulin G (GFAP-IgG) has not been well described.The aim this study was to report the frequency, clinical, and electrophysiological characteristics PN in GFAP-IgG-positive patients.This is a single-center retrospective observational study.GFAP-IgG-positive patients were retrospectively identified from Huashan Hospital Autoimmune Encephalitis Cohort between 2017 2021. Eight who presented other...
The aim of this study is to determine in indigenous Chinese ethnic groups the frequencies chemokine (SDF1 3'A) and receptors (CCR5 delta32, CCR5 m303, CCR2b 64I) HIV-1/AIDS restriction alleles. includes two cohorts; first comprised 3165 healthy subjects representing eight groups: Han (n = 1406), Uygur 316), Mongolia 134), Hui 386), Tibetan 330), Zhuang 378), Dai 101), Jingbo =114). second cohort consisted 330 HIV-1-infected (86 infected by sexual transmission 198 HIV-1-contaminated blood or...
SUMMARY Rabies viral vectors have become important components of the systems neuroscience toolkit, allowing both direct retrograde targeting projection neurons and monosynaptic tracing inputs to defined postsynaptic populations, but rapid cytotoxicity first-generation (ΔG) limits their use short-term experiments. We recently introduced second-generation, double-deletion-mutant (ΔGL) rabies vectors, showing that they efficiently retrogradely infect express recombinases effectively with little...
Background: Treg cells represent important viral reservoirs during chronic HIV infection. CD39 is closely involved in Treg-mediated immunosuppressive effects. However, expression on nTregs and mTregs a relationship with DNA levels infection still unclear. In this study, we analyzed the distribution of subsets association between subsets. Methods: Sixty-two HIV-infected patients different stages 14 uninfected individuals were enrolled. (CD4+CD25+CD127lowCD45RO-) (CD4+CD25+CD127lowCD45RO+)...
In recent years, optogenetic approaches have significantly advanced the experimental repertoire of cellular and functional neuroscience. Yet, precise reliable methods for specific expression tools remain challenging. this work, we studied transduction efficiency seven different adeno-associated virus (AAV) serotypes in primary cortical neurons revealed recombinant (r) AAV6 to be most efficient constructs under control cytomegalovirus (CMV) promoter. To further specify transgene, exchanged...
Mapping the connectivity of diverse neuronal types provides foundation for understanding structure and function neural circuits. High-throughput low-cost neuroanatomical techniques based on RNA barcode sequencing have potential to map circuits at cellular resolution a brain-wide scale, but existing Sindbis virus-based can only long-range projections using anterograde tracing approaches. Rabies virus complement approaches by enabling either retrograde labeling projection neurons or...