A5088552997- HIV Research and Treatment
- interferon and immune responses
- HIV/AIDS drug development and treatment
- SARS-CoV-2 and COVID-19 Research
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Hepatitis C virus research
- RNA modifications and cancer
- Viral gastroenteritis research and epidemiology
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Viral Infections and Immunology Research
- Chromosomal and Genetic Variations
- RNA Interference and Gene Delivery
- RNA regulation and disease
- COVID-19 Clinical Research Studies
- Cytomegalovirus and herpesvirus research
- Plant Virus Research Studies
- HIV/AIDS Research and Interventions
- Poxvirus research and outbreaks
- Viral Infections and Vectors
- Immune Response and Inflammation
- COVID-19 Impact on Reproduction
- Hepatitis B Virus Studies
- Virus-based gene therapy research
University of Science and Technology of China
2025
Chinese Academy of Medical Sciences & Peking Union Medical College
2015-2024
Beijing Hospital
2016-2022
Air Force Medical University
2020-2022
Shandong University
2020-2022
Ningbo First Hospital
2019-2022
Peking Union Medical College Hospital
2020-2022
Second Military Medical University
2020-2022
International Institute for Applied Systems Analysis
2022
National Center for Clinical Laboratories
2016-2021
The pandemic of COVID-19 has posed an unprecedented threat to global public health. However, the interplay between viral pathogen COVID-19, SARS-CoV-2, and host innate immunity is poorly understood. Here we show that SARS-CoV-2 induces overt but delayed type-I interferon (IFN) responses. By screening 23 proteins, find NSP1, NSP3, NSP12, NSP13, NSP14, ORF3, ORF6 M protein inhibit Sendai virus-induced IFN-β promoter activation, whereas NSP2 S exert opposite effects. Further analyses suggest...
Cas9 cleaves specific DNA sequences with the assistance of a programmable single guide RNA (sgRNA). Repairing this broken by cell's error-prone non-homologous end joining (NHEJ) machinery leads to insertions and deletions (indels) that often impair function. Using HIV-1, we have now demonstrated many these indels are indeed lethal for virus, but others lead emergence replication competent viruses resistant Cas9/sgRNA. This unexpected contribution development viral resistance is facilitated...
Highly active antiretroviral therapy (HAART) has transformed HIV-1 infection from a deadly disease to manageable chronic illness, albeit does not provide cure. The recently developed genome editing system called CRISPR/Cas9 offers new tool inactivate the integrated latent DNA and may serve as avenue toward cure.We tested 10 sites in that can be targeted by CRISPR/Cas9. engineered was introduced into JLat10.6 cells are latently infected HIV-1. sequencing results showed each target site...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the unprecedented disease 2019 (COVID-19) pandemic. Critical cases of COVID-19 are characterized by production excessive amounts cytokines and extensive lung damage, which is partially fusion SARS-CoV-2-infected pneumocytes. Here, we found that cell SARS-CoV-2 spike (S) protein induced a type I interferon (IFN) response. This function S required its cleavage proteases at S1/S2 S2' sites. We further showed damaged nuclei...
APOBEC3G, a member of an RNA/DNA cytidine deaminase superfamily, has been identified as cellular inhibitor HIV-1 infectivity, possibly through the dC to dU deamination first minus strand cDNA synthesized during reverse transcription. Virions incorporate APOBEC3G viral assembly in non-permissive cells, and this incorporation is inhibited by protein Vif. The mechanism into examined report. In absence Vif, cytoplasmic becomes membrane-bound cells expressing Gag, its Gag viral-like particles...
Cells are categorized as being permissive or nonpermissive according to their ability produce infectious human immunodeficiency virus type 1 (HIV-1) lacking the viral protein Vif. Nonpermissive cells express cytidine deaminase APOBEC3G (hA3G), and Vif has been shown bind facilitate its degradation. Vif-negative HIV-1 virions produced in incorporate hA3G have a severely reduced DNA newly infected cells. While it proposed that reduction production is due hA3G-facilitated deamination of...
Human APOBEC3G (hA3G) has been identified as an anti-HIV-1 host factor. The presence of hA3G in HIV-1 strongly inhibits the ability virus to produce new viral DNA upon infection. In this report, we demonstrate that reduction late synthesis is due inhibition by strand transfer steps occur during reverse transcription. Analysis cDNA intermediates vivo reveals causes minus and plus transfers, without having a significant impact on elongation. Using vitro system measure similarly shows...
Members of the interferon-induced transmembrane (IFITM) protein family inhibit entry a wide range viruses. Viruses often exploit endocytosis pathways to invade host cells and escape from endocytic vesicles in response low pH. Localization these is essential for IFITM3 interfere with cytosolic pH-dependent However, nature sorting signal that targets poorly defined. In this study, we report possesses YxxΦ motif, i.e. 20-YEML-23, enables undergo through binding μ2 subunit AP-2 complex....
The SAM domain and HD containing protein 1 (SAMHD1) inhibits retroviruses, DNA viruses long interspersed element (LINE-1). Given that in dividing cells, SAMHD1 loses its antiviral function yet still potently restricts LINE-1, we propose that, instead of blocking viral synthesis by virtue dNTP triphosphohydrolase activity, may exploit a different mechanism to control LINE-1. Here, report new activity promoting cellular stress granule assembly, which correlates with increased phosphorylation...
Antiviral therapeutics is one effective avenue to control and end this devastating COVID-19 pandemic. The viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 has been recognized as a valuable target antivirals. However, the cell-free RdRp biochemical assay requires conversion nucleotide prodrugs into active triphosphate forms, which regularly occurs in cells yet complicated multiple-step chemical process vitro, thus hinders utility rapid discovery inhibitors. In addition, exoribonuclease...
The cyclic GMP-AMP (cGAMP) synthase (cGAS) is a key DNA sensor that initiates STING-dependent signaling to produce type I interferons through synthesizing the secondary messenger 2′3′-cGAMP. In this study, we confirm previous studies showing cGAS located both in cytoplasm and nucleus. Nuclear accumulation observed when leptomycin B used block exportin, CRM1 protein. As result, impairs production of response stimulation. We further identify functional nuclear export signal (NES) cGAS,...
Abstract The membrane-associated RING-CH (MARCH) proteins are E3 ligases that regulate the stability of various cellular membrane proteins. MARCH8 has been reported to inhibit infection HIV-1 and a few other viruses, thus plays an important role in host antiviral defense. However, spectrum underlying mechanisms incompletely defined. Here, we demonstrate profoundly inhibits influenza A virus (IAV) replication both vitro mice. Mechanistically, suppresses IAV release through redirecting viral...
Abstract The emergence of new highly pathogenic and drug-resistant influenza strains urges the development novel therapeutics for A virus (IAV). Here, we report discovery an anti-IAV microbial metabolite called APL-16-5 that was originally isolated from plant endophytic fungus Aspergillus sp. CPCC 400735. binds to both E3 ligase TRIM25 IAV polymerase subunit PA, leading ubiquitination PA subsequent degradation in proteasome. This mode action conforms a proteolysis targeting chimera which...
Mpox is caused by a zoonotic virus belonging to the Orthopoxvirus genus and Poxviridae family. In this study, we develop recombinase polymerase amplification (RPA)-coupled CRISPR-Cas12a detection assay for mpox virus. We design test series of CRISPR-derived RNAs(crRNAs) targeting conserved D6R E9L genes orthopoxvirus unique N3R N4R viruses. crRNA-1 exhibits most robust activity in detecting orthopoxviruses, crRNA-2 able distinguish from other orthopoxviruses. The Cas12a/crRNA alone presents limit 10
ABSTRACT Human immunodeficiency virus type 1 (HIV-1) containing human APOBEC3G (hA3G) has a reduced ability to produce viral DNA in newly infected cells. At least part of this hA3G-facilitated inhibition is due cytidine deamination-independent reduction the initiate reverse transcription. HIV-1 nucleocapsid (NCp7) required both for incorporation hA3G into virions and annealing between RNA tRNA 3 Lys , primer Herein we present evidence that interaction with transcription initiation. A priming...
ABSTRACT Bone marrow stromal cell antigen 2 (BST-2, also known as tetherin) restricts the production of a number enveloped viruses by blocking virus release from surface. This antiviral activity is counteracted such viral factors Vpu human immunodeficiency type 1 (HIV-1). Here, we report that antagonizes BST-2 but not derived African green monkeys. The determinants susceptibility to map transmembrane domain BST-2. In accordance with this, expression containing modified effectively blocks...
LINE-1 (long interspersed element 1) is an autonomous non-long terminal repeat retrotransposon. Its replication often causes mutation and rearrangement of host genomic DNA. Accordingly, cells have evolved mechanisms to control mobility. Here, we report that a helicase named MOV10 effectively suppresses transposition. Mutating the motifs impairs this function MOV10, suggesting requires its activity suppress replication. Further studies show post-transcriptionally diminishes level RNA. The...
CRISPR-Cas provides bacteria and archaea with immunity against invading phages foreign plasmid DNA has been successfully adapted for gene editing in a variety of species. The class 2 type VI effector Cas13a targets cleaves RNA, providing protection RNA phages. Here we report the repurposing CRISPR-Cas13a to inhibit human immunodeficiency virus 1 (HIV-1) infection through targeting HIV-1 diminishing viral expression. We observed strong inhibition by cells. showed that not only diminishes...
The productive infection of influenza A virus (IAV) depends on host factors. However, the involvement long non-coding RNAs (lncRNAs) in IAV remains largely uninvestigated. In this work, we have discovered a human lncRNA, named lncRNA-PAAN (PA-associated noncoding RNA) that enhances replication. level increases upon IAV, but not other viruses, nor interferon treatment, suggesting specific up-regulation expression by IAV. Silencing significantly decreases replication through impairing activity...
Long noncoding RNAs (lncRNAs) participate in host antiviral defense by modulating immune responses. However, it remains largely unexplored how viruses exploit interferon (IFN)-independent lncRNAs to facilitate viral replication. Here, we have identified a group of human that modulate influenza A virus (IAV) replication loss-of-function screen and found an IFN-independent lncRNA, called IPAN, is hijacked IAV assist IPAN specifically induced infection independently IFN associates with...
Cyclic GMP-AMP synthase (cGAS) is a major sensor of cytosolic DNA from invading pathogens and damaged cellular organelles. Activation cGAS promotes liquid-like phase separation formation membraneless cytoplasmic structures. Here, we found that bound G3BP1, double-stranded nucleic acid helicase involved in the stress granules. Loss G3BP1 blocked subcellular condensation suppressed interferon response to intracellular virus particles cells. Furthermore, an RNA-dependent association with PKR...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become one major threat to human population health. The RNA-dependent RNA polymerase (RdRp) presents an ideal target of antivirals, whereas nucleoside analogs inhibitor is hindered by the proofreading activity coronavirus. Herein, we report that corilagin (RAI-S-37) as a non-nucleoside SARS-CoV-2 RdRp, binds directly effectively inhibits in both cell-free and cell-based assays, fully resists potently infection with low 50%...
In this study, we investigate the seroprevalence of SARS-CoV-2 antibodies among blood donors in cities Wuhan, Shenzhen, and Shijiazhuang China. From January to April 2020, 38,144 healthy three were tested for total antibody against followed by pseudotype neutralization tests, IgG, IgM testing. Finally, a 398 confirmed positive. The age- sex-standardized 18-60 year-old adults (18-65 Shenzhen) was 2.66% (95% CI: 2.24%-3.07%) 0.033% 0.0029%-0.267%) 0.0028% 0.0001%-0.158%) Shijiazhuang,...
Coronavirus disease 2019 (COVID-19) is a fatal respiratory illness caused by severe acute syndrome coronavirus 2 (SARS-CoV-2). The identification of potential drugs urgently needed to control the pandemic. RNA dependent polymerase (RdRp) conserved protein within viruses and plays crucial role in viral life cycle, thus making it an attractive target for development antiviral drugs. In this study, 101 quinoline quinazoline derivatives were screened against SARS-CoV-2 RdRp using cell-based...