Xiao-Fang Yu

Zhejiang University | ZJU · Cancer Institute

Despite the efficacy of highly active antiretroviral therapy in controlling the incidence and mortality of AIDS, effective interventions for HIV-1-induced neurological damage and cognitive impairment remain elusive. In this study, we found that HIV-1 infection can induce proteolytic cleavage and aberrant aggregation of TAR DNA-binding protein 43 (T...

Coronaviruses employ various strategies for survival, among which the activation of endogenous or exogenous apoptosis stands out, with viral proteins playing a pivotal role. Notably, highly pathogenic coronaviruses such as SARS-CoV-2, SARS-CoV, and MERS-CoV exhibit a greater array of non-structural proteins compared to low-pathogenic strains, facil...

HIV-1 replication is tightly regulated in host cells, and various restriction factors have important roles in inhibiting viral replication. SAMHD1, a well-known restriction factor, suppresses HIV-1 replication by hydrolyzing intracellular dNTPs, thereby limiting the synthesis of viral cDNA in quiescent cells. In this study, we revealed an additiona...

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The dysfunction of zinc homeostasis participates in the early and advancing malignancy of HCC. However, the prognostic ability of zinc homeostasis in HCC has not been clarified yet. Here, we showed a zinc-homeostasis related risk model in HCC. Five signatu...

Stimulatorof interferon genes (STING) is an intracellular sensor of cyclic dinucleotides involved in the innate immune response against pathogen‐ or self‐derived DNA. For years, interferon (IFN) induction of cyclic GMP–AMP synthase (cGAS)–STING has been considered as a canonical pattern defending the host from viral invasion. The mechanism of the c...

Pyroptosis plays a crucial role in the pathogenesis of coronavirus disease 2019, and comprehending its function may facilitate the development of novel therapeutic strategies. This study aims to explore how viral-encoded proteases modulate pyroptosis. We investigated the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and res...

Innate immunity represents one of the main host responses to viral infection.1–3 STING (Stimulator of interferon genes), a crucial immune adapter functioning in host cells, mediates cGAS (Cyclic GMP-AMP Synthase) sensing of exogenous and endogenous DNA fragments and generates innate immune responses.4 Whether STING activation was involved in infect...

Cellular infections by DNA viruses trigger innate immune responses mediated by DNA sensors. The cyclic GMP–AMP synthase (cGAS)‐stimulator of interferon gene (STING) signaling pathway has been identified as a DNA‐sensing pathway that activates interferons in response to viral infection and, thus, mediates host defense against viruses. Previous studi...

Recognizing aberrant cytoplasmic double-stranded DNA (dsDNA) and stimulating innate immunity are essential for the host defense against viruses and tumors. Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that synthesizes the second messenger 2'3'-cGAMP and subsequently activates stimulator of interferon genes (STING)-mediated activ...

Recognizing aberrant cytoplasmic dsDNA and stimulating cGAS‐STING‐mediated innate immunity are essential for the host defense against viruses. Recent studies have reported that SARS‐CoV‐2 infection, responsible for the COVID‐19 pandemic, triggers cGAS‐STING activation. cGAS‐STING activation can trigger IRF3‐type I interferon (IFN) and autophagy‐med...

The emergence of SARS-CoV-2 has resulted in the COVID-19 pandemic, leading to millions of infections and hundreds of thousands of human deaths. The efficient replication and population spread of SARS-CoV-2 indicates an effective evasion of human innate immune responses, although the viral proteins responsible for this immune evasion are not clear....

Gastric cancer (GC) is the third most common cause of cancer-related death in the word. Immunotherapy is a promising treatment of cancer. However, it is unclear which GC subpopulation would benefit most from immunotherapy and it is necessary to develop effective biomarkers for predicting immunotherapy response. Nicotinamide N-methyltransferase (NNM...

Background: Most colon adenocarcinoma (COAD) patients die of distant metastasis, though there are some therapies for metastatic COAD. However, the genes exclusively expressed in metastatic COAD remain unclear. This study aims to identify prognosis-related genes associated with distant metastasis and develop therapeutic strategies for COAD patients....

Mastoscopic axillary lymph node dissection (MALND) is a currently used and safe surgical treatment option for breast cancer. However, the extensive application of MALND is still debatable because of the use of conventional axillary lymph node dissection (CALND). Therefore, in the current study, we aimed to compare the efficacy and safety of MALND a...

Background Breast cancer (BC) is a disease with morbidity ranking the first of women worldwidely. FK506-binding protein (FKBP) family has been demonstrated to possess various functions by interacting with different molecular targets in BC. However, a comprehensive ncRNA-mRNA regulatory axis of FKBP has not yet been reported. Methods FKBP related mi...

Purpose: FKBP4 is a member of the immunophilin protein family, which plays a role in immunoregulation and basic cellular processes involving protein folding and trafficking associated with HSP90. However, the relationship between abnormal expression of FKBP4 and clinical outcome in luminal A subtype breast cancer (LABC) patients remains to be eluci...

SAMHD1 possesses multiple functions, but whether cellular factors regulate SAMHD1 expression or its function remains not well characterized. Here, by investigating why cultured RD and HEK293T cells show different sensitivity to enterovirus 71 (EV71) infection, we demonstrate that SAMHD1 is a restriction factor for EV71. Importantly, we identify TRI...

Innate immunity is the first line of host defence against pathogens. Suppression of innate immune responses is essential for the survival of all viruses. However, the interplay between innate immunity and HIV/SIV is only poorly characterized. We have discovered Vpx as a novel inhibitor of innate immune activation that associates with STING signalos...

The human adenovirus oncoprotein E4orf6 hijacks intracellular Cullin 5-based E3 ubiquitin ligases (CRL5s) to induce the degradation of host proteins, including p53, that impede efficient viral replication. The complex also relies on another viral protein, E1B55K, to recruit substrates for ubiquitination. However, the determinants of adenoviral E4or...

Human immunodeficiency virus (HIV) actively modulates the protein stability of host cells to optimize viral replication. To systematically examine this modulation in HIV infection, we used isobaric tag-based mass spectrometry to quantify changes in the abundance of over 14,000 proteins during HIV-1 infection of human primary CD4 ⁺ T cells. We ident...

The lentiviral accessory protein Vpx enhances viral replication in macrophages, dendritic cells and resting CD4 ⁺ T cells by utilizing the host CRL4-DCAF1 E3 ligase to trigger the degradation of the intrinsic antiviral factor SAMHD1. Distinct from the species-specific recognition of either the N[sbnd] or C-terminus of SAMHD1 by Vpx proteins of diff...

Interaction between HIV-1 Vif and host factor CBFβ leads to the assembly of the Vif-Cul5-EloB/C ubiquitin ligase (E3 complex). By inducing the formation of E3 complex, Vif depletes host APOBEC3 restriction factors and promotes HIV-1 infection. In addition, Vif is known to arrest host cells at G2/M phase (G2 arrest), benefiting HIV-1 replication and...

Although the host restriction factor APOBEC3G (A3G) has broad spectrum antiviral activity, whether A3G inhibits enterovirus 71 (EV71) has been unclear until now. In this study, we demonstrated for the first time that A3G could inhibit EV71 virus replication. Silencing A3G in H9 cells enhanced EV71 replication, and EV71 replication was lower in H9 c...

Coxsackievirus A6 (CV-A6) is an emerging pathogen associated with hand, foot, and mouth disease (HFMD). Its genetic characterization and pathogenic properties are largely unknown. Here, we report 39 circulating CV-A6 strains isolated in 2013 from HFMD patients in northeast China. Three major clusters of CV-A6 were identified and related to CV-A6, m...

The HIV-1 reservoir is a major obstacle to complete eradication of the virus. Although many proteins and RNAs have been characterized as regulators in HIV-1/AIDS pathogenesis and latency, only a few long non-coding RNAs (lncRNAs) have been shown to be closely associated with HIV-1 replication and latency. Here, we demonstrated that lncRNA uc002yug....

Improper host immune activation leads to the development of the autoimmune disease Aicardi-Goutières syndrome (AGS), which is attributed to defined genetic mutations in such proteins as TREX1 and ADAR1. The mechanism of immune activation in AGS patients has not been thoroughly elucidated to date. In this study, we report that endogenous LINE1 compo...

The lentiviral accessory protein Vpx is critical for viral infection of myeloid cells and acts by hijacking CRL4(DCAF1) E3 ubiquitin ligase to induce the degradation of the host restriction factor SAMHD1. It has been observed that the sequences from HIV-2 and SIVsmm/SIVmac Vpx contain a poly-proline tail which is distinct from other SIV Vpx protein...

Coxsackievirus A16 (CV-A16), CV-A6, and enterovirus D68 (EV-D68) belong to the Picornaviridae family and are major causes of hand, foot, and mouth disease (HFMD) and pediatric respiratory disease worldwide. The biological characteristics of these viruses, especially their interplay with the host innate immune system, have not been well investigated...

The lentiviral accessory proteins Vpx and Vpr are known to utilize CRL4 (DCAF1) E3 ligase to induce the degradation of the host restriction factor SAMHD1 or host helicase transcription factor (HLTF), respectively. Selective disruption of viral CRL4 (DCAF1) E3 ligase could be a promising antiviral strategy. Recently, we have determined that posttran...

Maintaining genome integrity is important for cells and damaged DNA triggers autoimmunity. Previous studies have reported that Three-prime repair exonuclease 1(TREX1), an endogenous DNA exonuclease, prevents immune activation by depleting damaged DNA, thus preventing the development of certain autoimmune diseases. Consistently, mutations in TREX1 a...

Importance: The conserved Vif accessory proteins of primate lentiviruses HIV-1, SIV, and BIV all form ubiquitin ligase complexes to target host antiviral APOBEC3 proteins for degradation, with different cellular requirements and using different molecular mechanisms. Here we demonstrate that BIV Vif can interfere with HIV-1 Gag maturation and suppr...

Enterovirus D68 (EV-D68) is an emerging pathogen that recently caused a large outbreak of severe respiratory disease in the United States and other countries. Little is known about the relationship between EV-D68 virus and host cells. In this study, we assessed the effect of the host cell cycle on EV-D68 viral production, as well as the ability of...

Figure S1. The N‐glycosylation potential of (A) CC‐16‐43‐Mar‐2015, (B) BJ/55258‐May‐2014 and (C) BJ/39979‐Nov‐2012.

Enterovirus D68 (EV-D68) is a member of the Picornaviridae family. Although EV-D68-associated infection was once considered rare, it has been increasing in recent years. EV-D68 infection is most frequently associated with respiratory illness. However, it has also been implicated in a polio-like neurological disorder, acute flaccid myelitis. Althoug...

Human long interspersed elements 1 (LINE-1 or L1) is the only autonomous non-LTR retroelement in humans and has been associated with genome instability, inherited genetic diseases, and the development of cancer. Certain human APOBEC3 family proteins are known to have LINE-1 restriction activity. The mechanisms by which APOBEC3 affects LINE-1 retrot...

Although human respiratory syncytial virus (RSV) is one of the most common viruses inducing respiratory tract infections in young children and the elderly, the genotype distribution and characteristics of RSV in northeastern China have not been investigated. Here, we identified 25 RSV-A and 8 RSV-B strains from 80 samples of patients with respirato...

Supplementary figures.

Highlights • Naturally occurring HIV-1capsid variants confer HIV-1 resistance to MxB. •MxB-resistant capsid A116 is a major variant in HIV-1 Subtype C. •HIV-1 capsid variant A116 is accumulating during expansion of the HIV-1 epidemic in China. •MxB-resistant HIV-1 capsid variants maintain interaction with MxB. Interferon (IFN) is a key component of...

Human APOBEC3 cytidine deaminases are intrinsic resistance factors to HIV-1. However, HIV-1 encodes a viral infectivity factor (Vif) that degrades APOBEC3 proteins. In vitro APOBEC3F (A3F) anti-HIV-1 activity is weaker than A3G but is partially resistant to Vif degradation unlike A3G. It is unknown whether A3F protein affects HIV-1 disease in vivo....

Distribution of A3F-231I/V in the HIV-1 negative and positive groups. (DOCX)

HIV-1 hypermutations detected from patients in the Swiss HIV Cohort Study, stratified by the A3F- rs2076101 genotypes. (DOCX)

Kaplan-Meier survival curves of A3F-231I/V genotype carriers for progression to PCP since HIV-1 infection in 278 African American seroconverters. RH and adjusted P values were obtained from the Cox proportional hazards model. P values for survival curves were obtained from the log-rank test. (TIFF)

Summary of cohorts in the International Collaboration for the Genomics of HIV (ICGH) consortium used for HIV-1 viral load analysis. (DOCX)

Linkage disequilibrium in the APOBEC3 gene region. Data was based on HapMap phase III data in the CEU (Utah Caucasian) population and was plotted with Haploview. The intensity of the box reflects the r2 level and haplotype block was defined by 95% CI. (TIFF)

Frequency distribution of A3F-231I/V genotypes in European Americans of fast progressors and slow progressors. (TIFF)

BST-2/tetherin blocks the release of various enveloped viruses including HIV-1 with a “physical tethering” model. The detailed contribution of N-linked glycosylation to this model is controversial. Here, we confirmed that mutation of glycosylation sites exerted an effect of post-translational mis-trafficking, leading to an accumulation of BST-2 at...

Coxsackievirus A16 (CA16) and enterovirus 71 (EV71) are two main causative pathogens of hand, foot and mouth disease (HFMD). Unlike EV71, virulence determinants of CA16, particularly within 5′ untranslated region (5′UTR), have not been investigated until now. Here, a series of nucleotides present in 5′UTR of lethal but not in non-lethal CA16 strain...

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring au...

The human immunodeficiency virus type 1 (HIV-1) envelope (Env) plays a critical role in viral replication and represents a potential target for host antiviral factors. Recent work by Tada and colleagues identifies membrane-associated-RING-CH8 (MARCH8) as a potent anti-HIV factor blocking virion incorporation of Env. Thus, MARCH8 joins a growing lis...

Primate SAMHD1 proteins are potent inhibitors of viruses, including retroviruses such as HIV-1, HIV-2, and SIV. Vpx, a distinctive viral protein expressed by HIV-2 and some SIVs, induces SAMHD1 degradation by forming a Vpx-DCAF1-based ubiquitin ligase complex. Either the N- or the C-terminus of SAMHD1 is critical for Vpx-induced degradation, depend...

Enterovirus 68 (EVD68) causes respiratory illness, mostly in children. Despite a reported low-level of transmission, the occurrence of several recent outbreaks worldwide including the 2014 outbreak in North America has raised concerns regarding the pathogenesis and evolution of EVD68. To elucidate the phylogenetic features of EVD68 and possible cau...

EVD68 strains used in this study. (DOCX)

Primary squamous cell carcinoma of the thyroid is a rare and aggressive type of neoplasm, which is routinely treated with surgery; however, despite this, survival time is not commonly more than six months. Thus, the aim of the present study was to determine the efficacy of pseudolaric acid (PAB) as a therapeutic agent. PAB is an antitubulin agent,...

Sterile α-motif/histidine-aspartate domain-containing protein (SAMHD1), a homo-tetrameric GTP/dGTP-dependent dNTP triphosphohydrolase, catalyzes the conversion of dNTP into deoxynucleoside and triphosphate. As the only characterized dNTP triphosphohydrolase in human cells, SAMHD1 plays an important role in human innate immunity, autoimmunity, and c...

Coxsackievirus A16 (CA16) and enterovirus 71 (EV71), both of which can cause hand, foot and mouth disease (HFMD), are responsible for large epidemics in Asian and Pacific areas. Although inactivated EV71 vaccines have completed testing in phase III clinical trials in Mainland China, CA16 vaccines are still under development. A Vero cell-based inact...

Circulating enterovirus 71 (EV-A71)-associated hand, foot, and mouth disease is on the rise in the Asian-Pacific region. Although animal models have been developed using mouse-adapted EV-A71 strains, mouse models using primary EV-A71 isolates are scarce. Lethal animal models with circulating EV-A71 infection would contribute to studies of pathogene...

BST-2/tetherin is an interferon-inducible antiviral protein that blocks the release of various enveloped viruses, including HIV-1. Hepatitis B virus (HBV), a major cause of liver disease, belongs to the Hepadnaviridae family of enveloped DNA viruses. Whether BST-2 regulates HBV production is largely unknown. In this report, we have demonstrated tha...

Circulating enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) is a major public health problem in the Asian-Pacific region. An EV71 vaccine for HFMD prevention is currently being developed. However, viral determinants that could influence the vaccine's efficacy have not been well characterized. In this study, we isolated and cha...

An enterovirus 71 (EV71) vaccine for the prevention of hand, foot, and mouth disease (HMFD) is available, but it is not known whether the EV71 vaccine cross-protects against Coxsackievirus (CV) infection. Furthermore, although an inactivated circulating CVA16 Changchun 024 (CC024) strain vaccine candidate is effective in newborn mice, the CC024 str...

SAMHD1 is the only known eukaryotic deoxynucleoside triphosphate triphos­phohydrolase (dNTPase) and is a major regulator of intracellular dNTP pools. It has been reported to be a potent inhibitor of retroviruses such as HIV-1 and endogenous retrotransposons. Previous crystal structures have revealed that SAMHD1 is activated by dGTP-dependent tetram...

Although the Vpr protein of human immunodeficiency virus type 1 (HIV-1) has been shown to act as a transcriptional activator of the HIV-1 LTR and certain host genes, the current study demonstrates that it can also function as a potent inhibitor of the cytomegalovirus (CMV) promoter. Previous studies have shown that the cell cycle arrest and apoptot...

Many viruses disrupt the host cell cycle to facilitate their own growth. We assessed the mechanism and function of enterovirus 71 (EV71), a primary causative agent for recent hand, foot, and mouth disease outbreaks, in manipulating cell cycle progression. Our results suggest that EV71 infection induces S-phase arrest in diverse cell types by preven...

Abstract HIV-1 Vif assembles the Cul5-EloB/C E3 ubiquitin ligase to induce proteasomal degradation of the cellular antiviral APOBEC3 proteins. Detailed structural studies have confirmed critical functional domains in Vif that we have previously identified as important for the interaction of EloB/C, Cul5, and CBFβ. However, the mechanism by which Vi...

The deoxynucleoside triphosphate triphosphohydrolase SAMHD1 is a myeloid cell-specific retroviral restriction factor that can be inactivated by viral protein Vpx from HIV-2 and certain SIV. In this issue of Cell Host & Microbe, Kyei et al. (2015) report that cyclin L2 enhances HIV-1 infection in macrophages by regulating SAMHD1. Copyright © 2015 El...

In order to meet the requirement of determining the azimuth angles in fabricating optical devices from photonic crystal fibers (PCFs), a method based on analyzing the forward scattering patterns is proposed. The PCF sample is illuminated transversely by a laser of 650 nm, and the forward scattering patterns and the tip microscopic images are simult...

Background Human immunodeficiency virus type 1 (HIV-1) Vif hijacks an E3 ligase to suppress natural APOBEC3 restriction factors, and core binding factor ß (CBF-ß) is required for this process. Although an extensive region of Vif spanning most of its N-terminus is known to be critical for binding with CBF-ß, involvement of the Vif C-terminus in the...