Qiliang Cai

Fudan University · Department of Microbiology and Parasitology

Epstein-Barr virus (EBV), an oncogenic herpesvirus, is predominantly found in the latent infection form and is highly associated with many human malignancies, which mainly have poor prognoses and no effective treatments. Here, we obtained thirteen compounds from small-molecule libraries for specific inhibition of EBV-latently infected cell growth i...

The metabolic reprogramming of aerobic glycolysis contributes to tumorigenesis. High plasma lactate is a critical regulator in the development of many human malignancies; however, the underlying molecular mechanisms of cancer progression in response to lactate (LA) remain elusive. Here, we show that the reduction of Yin-Yang 1 (YY1) expression corr...

Background: Aurora kinase A (AURKA) is a potent oncogene that is often aberrantly expressed during tumorigenesis, and is associated with chemo-resistance in various malignancies. However, the role of AURKA in chemo-resistance remains largely elusive. Methods: The cleavage of AURKA upon viral infection or apoptosis stimuli was assesed by immunoblott...

TRIM32 is often aberrantly expressed in many types of cancers. Kaposi’s sarcoma-associated herpesvirus (KSHV) is linked with several human malignancies, including Kaposi’s sarcoma and primary effusion lymphomas (PELs). Increasing evidence has demonstrated the crucial role of KSHV lytic replication in viral tumorigenesis. However, the role of TRIM32...

Dysregulation of long noncoding RNA (lncRNA) expression plays a pivotal role in the initiation and progression of gastric cancer (GC). However, the regulation of lncRNA SNHG15 in GC has not been well studied. Mechanisms for ferroptosis by SNHG15 have not been revealed. Here, we aimed to explore SNHG15‐mediated biological functions and underlying mo...

Despite prolonged surveillance and interventions, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses continue to pose a severe global health burden. Thus, we developed a chimpanzee adenovirus-based combination vaccine, AdC68-HATRBD, with dual specificity against SARS-CoV-2 and influenza virus. When used as a stan...

Background Helicobacter pylori (H pylori) infection is the primary cause of gastric cancer (GC). The role of Disabled-2 (DAB2) in GC remains largely unclear. This study aimed to investigate the role of DAB2 in H pylori-mediated gastric tumorigenesis. Methods We screened various datasets of GC to analyze DAB2 expression and cell signaling pathways....

Background After the eradication of smallpox in China in 1979, vaccination with the vaccinia virus (VACV) Tiantan strain for the general population was stopped in 1980. As the monkeypox virus (MPXV) is rapidly spreading in the world, we would like to investigate whether the individuals with historic VACV Tiantan strain vaccination, even after more...

Developing broad-spectrum vaccines and optimal vaccination strategies is crucial to controlling the COVID-19 pandemic. Here, we generated a chimpanzee adenoviral vector-based COVID-19 vaccine carrying broad-spectrum immunogens, modified full-length spike, and conserved T-cell epitopes of SARS-CoV-2, and assessed its immune response in mice through...

Background: Lactate is associated with the poor prognosis of many human malignancies. Cervical cancer, one of main causes of women mortality worldwide, is aggressive and absent of effective pharmacological treatment, and its underlying mechanisms of progression remain elusive. Methods: The regulation of β-catenin to fascin protrusion formation upon...

Parainfluenza virus 5 (PIV5) is a negative-sense, single-stranded RNA virus that can infect humans and many species of animals. Infection in these reservoir hosts is generally asymptomatic and has few safety concerns. Emerging evidence has shown that PIV5 is a promising vector for developing vaccines against human infectious diseases caused by coro...

Golgi membrane protein 1 (GOLM1) is aberrantly expressed in many types of solid tumors and contributes to cancer development; however, its role in hematopoietic and lymphoid neoplasms remains unknown. Here, we report that GOLM1 was significantly upregulated in anaplastic large cell lymphoma (ALCL), particularly in anaplastic lymphoma kinase-positiv...

The key structure of the interface between the spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and human angiotensin-converting enzyme 2 (hACE2) acts as an essential switch for cell entry by the virus and drugs targets. However, this is largely unknown. Here, we tested three peptides of spike receptor binding domain (R...

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Aggressive B-cell lymphoma is one of the most common types of blood malignancy. Robust delivery of genes of interest into target cells, long-term gene expression, and minimal risk of secondary effects are highly desirable for translational medicine including gene therapy and studies on gene function. However, efficient gene delivery into viral or n...

Since the outbreak of Coronavirus Disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, global public health and the economy have suffered unprecedented damage. Based on the increasing related literatures, the characters and pathogenic mechanisms of the virus, epidemiological and clinical features...

Gastrointestinal (GI) diseases, including pathological dysplasia, inflammation, neoplasia and injury, suffer millions of patients globally per year. Organoids, three-dimensional cell mass structures supported by biomaterials in dishes, are currently used as a research model for diseases of the small intestine. However, the traditional enzymatic-dig...

Sex differences in immune responses had been reported to correlate with different symptoms and mortality in the disease course of coronavirus disease 2019 (COVID-19). However, whether severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection interferes with females’ fertility and causes different symptoms among pregnant and non-pregnant...

Kaposi’s sarcoma-associated herpesvirus (KSHV) has been reported to be involved in the regulation of host proteins in response to hypoxic stress. LANA, one of the key latent proteins, contains a SUMO-interacting motif (LANA SIM ) and reduces the association with SUMOylated KAP1 upon hypoxic treatment.

Reprogramming of energy metabolism is a key for cancer development. Kaposi’s sarcoma-associated herpesvirus (KSHV), a human oncogenic herpesvirus, is tightly associated with several human malignancies by infecting B-lymphocyte or endothelial cells. Cancer cell energy metabolism is mainly dominated by three pathways of central carbon metabolism, inc...

The global spread of SARS-CoV-2 is posing major public health challenges. One feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site. Here, we find that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disr...

High plasma lactate is emerging as a critical regulator in development and progression of many human malignancies. Small RNAs derived from cleavage of mature tRNAs have been implicated in many cellular stresses, but the detailed mechanisms that respond to lactic acid (LA; acidic lactate) are not well defined. Here, using an Epstein-Barr virus (EBV)...

The global spread of SARS-CoV-2 is posing major public health challenges. One unique feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site, the function of which remains uncertain. We found that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane...

Post-translational modification of target proteins by the Small Ubiquitin-like Modifier (SUMO) plays a critical role in regulation of many cellular processes including transcription, RNA processing, protein trafficking, DNA repair, and chromosome segregation, and is also often hijacked by viral infections. Epstein-Barr Virus (EBV) and Kaposi’s sarc...

Latent Epstein-Barr virus (EBV) infection is strongly associated with several malignancies, including B-cell lymphomas and epithelial tumors. EBNA1 is a key antigen expressed in all EBV-associated tumors during latency that is required for maintenance of the EBV episome DNA and the regulation of viral gene transcription. However, the mechanism util...

Primary effusion lymphoma (PEL) is an aggressive B-cell malignancy without effective treatment, and caused by the infection of Kaposi’s sarcoma-associated herpesvirus (KSHV), predominantly in its latent form. Previously we showed that the SUMO2-interacting motif within the viral latency-associated nuclear antigen (LANASIM) is essential for establis...

Based on measles surveillance in Shanghai, People’s Republic of China, from 2006 to 2015, we found that measles virus isolates from 40 throat swab samples exhibited atypical cytopathic effects in Vero/hSLAM cells, which was found to be a result of coinfection with measles virus (MeV) and human herpes simplex virus type 1 (HSV-1). Serological and mo...

Silver nanoparticle (nAg), which is one of the most common manufactured nanomaterials, has a wide range of biomedical applications. The human oncogenic γ-herpesviruses, Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein–Barr Virus (EBV), are etiologically linked to many malignancies. Currently, there are no efficient or specific treatments...

Graphical Abstract Highlights d Cleaved AURKB exists in many oncovirus-related cancer cells and patient cancer tissue d Oncovirus-mediated AURKB cleavage occurs at Asp 76 and relies on a serine protease d The N 0-AURKB promotes the metaphase-to-telophase transition in mitotic cells d The N 0-AURKB promotes tumor growth and malignancy in vitro and i...

The interaction between programmed cell death protein 1 (PD-1) on activated T cells and its ligands on a target tumour may limit the capacity of chimeric antigen receptor (CAR) T cells to eradicate solid tumours. PD-1 blockade could potentially enhance CAR T cell function. Here, we show that mesothelin is overexpressed in human triple-negative brea...

Aberrations in STAT6-mediated signaling are linked to the development of multiple cancer types. Increasing evidence has shown that activation of human oncogenic herpesvirus lytic replication is crucial for viral tumorigenesis. However, the role of STAT6 in herpesvirus lytic replication remains elusive. Here, by using Kaposi’s sarcoma-associated her...

RTA did not localize with STAT6 Y641F mutant. 293T cells transfected with FLAG-STAT6 Y641F in the presence of RFP-RTA or RFP vector were subjected to immunofluorescent assays with RFP (red) and FLAG (green) antibody. Nuclei were stained with DAPI. (TIF)

(A) Schematic of putative STAT6, RBP-Jκ and HIFα-binding sites within TRIML2 and AIM1 promoters. (B) STAT6 bound to TRIML2 and AIM1 promoter and enhanced by reactivation of lytic cycle. BCBL1 cells with or without TPA and sodium butyrate (NaB) treatment were subjected to Chromatin immunoprecipitation (ChIP) with endogenous STAT6. Non-specific rabbi...

Primers used in this study. (DOC)

Exogenous LC3 responds to different cell stress. HEK293T cells were transfected with GFP-LC3 expressing plasmid. At 24h post-transfection, cells were untreated (Mock), or individually treated with hypoxia (0.2% oxygen), TPA and sodium butyrate (TPA/NaB), and sera starvation for 12 h before fixed and nuclear staining (Blue) for immunofluorescent ass...

RTA-induced STAT6 degradation significantly turns over cellular gene expression of iSLK cells. (A) The iSLK cells with doyxycline (Dox)-induced RTA were transfected with exogenous STAT6 or vector alone. At 24hr post-transfection, cells were treated with doyxycline for 24hr before harvesting and lysing for immunoblotting. The relative levels of viri...

Establishment of PEL cells with STAT6 knockdown. BC3 and BCBL1 cells were individually infected with lentivirus carrying shSTAT6 or shCtrl control. Immunoblotting analysis of endogenous STAT6 and GAPDH were carried out as indicated in the figure. (TIF)

RTA inhibits STAT6 expression. (A) RTA reduces exogenous STAT6 expression in a dose-dependent manner. HEK293T cells co-transfected FLAG-STAT6 with different dosages (0, 1, 2, 5μg) of RTA-myc were subjected to immunoblotting as indicated in the figure. GFP-NLS-myc was used as a parallel control. The relative density (RD) of exogenous STAT6 and GFP-N...

RTA induces Myd88-FLAG for proteasome-mediated degradation. HEK293 cells were co-transfected with the indicated expressing plasmids. At 48hr post-transfection, cells were individually treated with or without 20μM MG132 for 3h before harvesting and lysing for immunoblotting. (TIF)

STAT6 knockdown enhances the levels of RTA and TRIML2 expression and virion production in PEL cells. BCBL1 cells were individually infected with lentivirus carrying shSTAT6 or shCtrl control. Equal amounts of knockdown cells were subjected to immunoblotting analysis with antibodies against STAT6, TRIML2 and RTA, and the virion titer in the supernat...

Cellular RNA decay machinery plays a vital role in regulating gene expression by altering the stability of mRNAs in response to external stresses, including viral infection. In the primary infection, viruses often conquer the host cell’s antiviral immune response by controlling the inherently cellular mRNA degradation machinery to facilitate viral...

Cover Caption: The cover image, by Ling Ding et al., is based on the Research Article High prevalence and correlates of human herpesvirus‐6A in nevocytic nevus and seborrheic diseases: Implication from a pilot study of skin patient tissues in Shanghai, DOI: 10.1002/jmv.25262.

Skin disorders vary greatly in symptoms and severity, and the causes of these disorders are largely unknown. Human herpesvirus (HHV) has been shown to cause many diseases. However, the prevalence and correlate of each HHV infection with different skin disorders remains obscure. To reveal the potential link of certain type of skin disease with herpe...

High plasma lactate is associated with poor prognosis of many malignancies, but its role in virally mediated cancer progression and underlying molecular mechanisms are unclear. Epstein–Barr virus (EBV), the first human oncogenic virus, causes several cancers, including B cell lymphoma. Here, we report that lactate dehydrogenase (LDH-A) expression a...

Emerging evidence has shown that the cell of microenvironmental abnormalities is a key factor that controls many cellular physiological processes including cellular communication, homing, proliferation, and survival. Given its central regulatory role, it is therefore not surprising that it is widely exploited by infectious agents for inducing patho...

Bacterial infections were traditionally not considered as major causes of cancer. However, increasing evidence in the past decades has suggested that several cancers are highly associated with bacterial infection. The bacterial infections have evolved some unique strategies including lateral gene transfer, biofilm and microbiome to induce genome in...

Activation of specific sets of protein kinases by intracellular signal molecules has become more and more apparent in the past decade. Phosphorylation, one of key posttranslational modification events, is activated by kinase or regulatory protein and is vital for controlling many physiological functions of eukaryotic cells such as cell proliferatio...

Dedicator of cytokinesis 8 (DOCK8) deficiency is a primary immunodeficiency, caused by biallelic loss-of-function mutations in the DOCK8 gene, often leading to severe viral infections, but do not usually have epidermodysplasia verruciformis (EV).1,2 Here we report a Chinese patient with unusual coexistence of gross generalized molluscum contagiosum...

Glioblastoma (GBM) is the most prevalent and lethal type of primary malignant brain tumour. Recent studies suggest that the discovery of human cytomegalovirus (HCMV)-encoded microRNAs (miRNAs) might play a role in the pathogenesis of diseases, including GBM. In this study, we aimed to analyse the expression and function of HCMV-encoded miRNAs in GB...

Emerging evidence implies that STAT6 plays an important role in both the adaptive and innate immune responses to virus infection. Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus agent associated with several human malignancies, including Kaposi’s sarcoma (KS) and primary effusion lymphomas (PELs). Previously, we demonst...

HEK293 cells transfected with truncated mutants (ΔN, ΔTAD, ΔDBD) of STAT6 with FLAG tag (green) in the presence or absence of LANA with RFP tag (red) imaged by confocal assay. Nuclei were stained with DAPI. The relative percentage of STAT6 nuclear localization (bottom panel) was individually quantified by nuclear and cytoplasmic staining of 100 cel...

Introduction of intact STAT6 inhibits RTA transcription and virion production. K-iSLK cells (mock) or K-iSLK cells transfected with wild-type (WT) or DBD-deleted mutant (ΔDBD) of exogenous STAT6 or vector alone, at 48hr post-transfection, were individually treated with TPA/Sodium butyrate for 24 hr before harvest. Equal amounts of cells were used t...

STAT6 knockdown reduces KSHV-infected BC3 cell growth. PEL BC3 cells were individually transfected shSTAT6 or shCtrl control. Equal amounts (2.5 million) of transfected cells were seeded and monitored the cell growth for 3 days. (TIF)

STAT6 inhibits RTA promoter but not its mutant with STAT6-binding site mutation or LANA promoter in a dose-dependent manner. HEK293 cells co-transfected with the indicated promoter-reporters at different dosages (0, 2, 5μg) of FLAG-STAT6 were subjected to reporter assay. Relative luciferase unit (RLU) normalization with Rellina activity was analyze...

The cell membrane regulates many physiological processes including cellular communication, homing and metabolism. It is therefore not surprising that the composition of the host cell membrane is manipulated by intracellular pathogens. Among these, the human oncogenic herpesviruses Epstein–Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus...

Post-translational modification of proteins with ubiquitin/small ubiquitin-like modifier (SUMO) molecules triggers multiple signaling pathways that are critical for many aspects of cellular physiology. Given that viruses hijack the biosynthetic and degradative systems of their host, it is not surprising that viruses encode proteins to manipulate th...

Hypoxia-inducible factor (HIF)-1 is a central regulator in the adaptation process of cell response to hypoxia (low oxygen). Emerging evidence has demonstrated that HIF-1 plays an important role in the development and progression of many types of human diseases, including pathogen-associated cancers. In the present review, we summarize the recent un...

Background: Mycoplasma genitalium (M. genitalium) has been shown to be involved in chronic non-gonococcal urethritis (NGU). However, the prevalence and determinants of this emerging sexually transmissible infection among prostatitis patients remain obscure. Methods: Two hundred and thirty-five patients diagnosed with prostatitis and 152 health cont...

Manipulation of cell cycle is a commonly employed strategy of viruses for achieving a favorable cellular environment during infection. Kaposi’s sarcoma-associated herpesvirus (KSHV), the primary etiological agent of several human malignancies including Kaposi’s sarcoma, and primary effusion lymphoma, encodes several oncoproteins that deregulate nor...

Activation of the Janus Kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway has been associated with numerous human malignancies, including primary effusion lymphomas (PELs). PEL, a cancerous proliferation of B-cells, is caused by the Kaposi's sarcoma-associated herpesvirus (KSHV). Previously we identified constit...

Major histocompatibility class II (MHC II) molecules play central role in adaptive antiviral immunity by presenting viral peptides to the CD4+ T cells. Due to their key role in adaptive immunity, many viruses including Kaposi's sarcoma associated herpesvirus (KSHV) have evolved multiple strategies to inhibit MHC II antigen presentation pathway. Exp...

The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latent nuclear antigen LANA plays an essential role in viral episome maintenance. LANA also contributes to DNA replication and tumorigenesis during latency. Recent studies suggested that LANA was involved in regulation of SUMOylation which results in chromatin silencing. To examine the plei...

Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, can latently infect the human population. EBV is associated with several types of malignancies originating from lymphoid and epithelial cell types. EBV latent antigen 3C (EBNA3C) is essential for EBV-induced immortalization of B-cells. The Moloney murine leukemia provirus integration site (P...

Unlabelled: Hypoxia-inducible factor 1α (HIF-1α) has been frequently implicated in many cancers as well as viral pathogenesis. Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to several human malignancies. It can stabilize HIF-1α during latent infection and undergoes lytic replication in response to hypoxic stress. However, the mechanism...

Author Summary Hypoxia stress is a common feature of tumor microenvironment and is widely associated with pathogenesis linked to many oncogenic viruses. Kaposi's sarcoma-associated herpesvirus (KSHV), the etiological cause of Kaposi's sarcoma and primary effusion lymphoma, has been reported to encode several proteins that usurp hypoxia signaling du...