A5025785786- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- interferon and immune responses
- Microbial Natural Products and Biosynthesis
- RNA and protein synthesis mechanisms
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Immunology Research
- Viral gastroenteritis research and epidemiology
- Influenza Virus Research Studies
- Hepatitis C virus research
- RNA modifications and cancer
- Viral Infections and Vectors
- Hepatitis B Virus Studies
- Mosquito-borne diseases and control
- Immune Cell Function and Interaction
- Respiratory viral infections research
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Fungal Biology and Applications
- Computational Drug Discovery Methods
- Chromosomal and Genetic Variations
- HIV/AIDS Research and Interventions
- COVID-19 Clinical Research Studies
Chinese Academy of Medical Sciences & Peking Union Medical College
2016-2025
Peking Union Medical College Hospital
2013-2025
Academy of Medical Sciences
2020-2023
Institute of Medicinal Plant Development
2013-2021
Beijing Friendship Hospital
2020
Capital Medical University
2020
Jewish General Hospital
2003-2013
McGill University
1999-2013
Nanjing Agricultural University
2013
China Academy of Chinese Medical Sciences
2011
Coronaviruses (CoVs) act as cross-species viruses and have the potential to spread rapidly into new host species cause epidemic diseases. Despite severe public health threat of acute respiratory syndrome coronavirus Middle East CoV (MERS-CoV), there are currently no drugs available for their treatment; therefore, broad-spectrum inhibitors emerging endemic CoVs urgently needed. To search effective inhibitory agents, we performed high-throughput screening (HTS) a 2,000-compound library...
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...
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...
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...
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...
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...
The human myxovirus-resistance protein B (MxB, also called Mx2) was recently reported to inhibit HIV-1 infection by impeding the nuclear import and integration of viral DNA. However, it is currently unknown whether there exist MxB-resistant strains in infected individuals. Answer this question should address MxB exerts an inhibitory pressure on vivo has evolved evade inhibition.We have examined ten transmitted founder (T/F) for their sensitivity inhibition infecting CD4+ T cell lines SupT1...
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...
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%...
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...
Human papillomavirus (HPV) infections account for several human cancers. There is an urgent need to develop therapeutic vaccines targeting preexisting high-risk HPV (such as 16 and 18) lesions, which are insensitive preventative vaccines. In this study, we developed a lipid nanoparticle–formulated mRNA-based vaccine (mHTV), mHTV-02, the E6/E7 of HPV16 HPV-18. mHTV-02 dramatically induced antigen-specific cellular immune response robust memory T-cell immunity in mice, besides significant CD8...
During human immunodeficiency virus type 1 (HIV-1) assembly, tRNA(Lys) isoacceptors are selectively incorporated into virions and tRNA(Lys)3 is used as the primer for reverse transcription. We show herein that tRNA(Lys)-binding protein, lysyl-tRNA synthetase (LysRS), also packaged HIV-1. The viral precursor protein Pr55gag alone will package LysRS particles, independently of tRNA(Lys). With additional presence Pr160gag-pol, both particle. While predominant cytoplasmic has an apparent M(r)...