Humans ; Herpesvirus 4, Human ; Wiskott-Aldrich Syndrome ; Epstein-Barr Virus Infections/complications* ; Smooth Muscle Tumor/therapy* ; Hematopoietic Stem Cell Transplantation

Viral infections cause at least 10%-15% of all human carcinomas. Over the last century, the elucidation of viral oncogenic roles in many cancer types has provided fundamental knowledge on carcinogenetic mechanisms and established a basis for the early intervention of virus-related cancers. Meanwhile, rapidly evolving genome-editing techniques targeting viral DNA/RNA have emerged as novel therapeutic strategies for treating virus-related carcinogenesis and have begun showing promising results. This review discusses the recent advances of genome-editing tools for treating tumorigenic viruses and their corresponding cancers, the challenges that must be overcome before clinically applying such genome-editing technologies, and more importantly, the potential solutions to these challenges.
Antiviral Agents ; therapeutic use ; CRISPR-Cas Systems ; Carcinoma ; genetics ; therapy ; virology ; Gene Editing ; Genetic Predisposition to Disease ; Genetic Therapy ; methods ; Humans ; Tumor Virus Infections ; complications

BACKGROUNDEpstein-Barr virus (EBV) commonly infects the general population and has been associated with nasopharyngeal carcinoma (NPC), which has a high incidence in certain regions. This study aimed to address how EBV variations contribute to the risk of NPC.

METHODSUsing logistic regression analysis and based on the sequence variations at EBV-encoded RPMS1, a multi-stage association study was conducted to identify EBV variations associated with NPC risk. A protein degradation assay was performed to characterize the functional relevance of the RPMS1 variations.

RESULTSBased on EBV-encoded RPMS1 variations, a single nucleotide polymorphism (SNP) in the EBV genome (locus 155391: G>A, named G155391A) was associated with NPC in 157 cases and 319 healthy controls from an NPC endemic region in South China [P < 0.001, odds ratio (OR) = 4.47, 95% confidence interval (CI) 2.71-7.37]. The results were further validated in three independent cohorts from the NPC endemic region (P < 0.001, OR = 5.20, 95% CI 3.18-8.50 in 168 cases vs. 241 controls, and P < 0.001, OR = 5.27, 95% CI 4.06-6.85 in 726 cases vs. 880 controls) and a non-endemic region (P < 0.001, OR = 7.52, 95% CI 3.69-15.32 in 58 cases vs. 612 controls). The combined analysis in 1109 cases and 2052 controls revealed that the SNP G155391A was strongly associated with NPC (P(combined) < 0.001, OR = 5.27, 95% CI 4.31-6.44). Moreover, the frequency of the SNP G155391A was associated with NPC incidence but was not associated with the incidences of other EBV-related malignancies. Furthermore, the protein degradation assay showed that this SNP decreased the degradation of the oncogenic RPMS1 protein.

CONCLUSIONSOur study identified an EBV variation specifically and significantly associated with a high risk of NPC. These findings provide insights into the pathogenesis of NPC and strategies for prevention.

Adult ; Aged ; Carcinoma ; Case-Control Studies ; China ; epidemiology ; Epstein-Barr Virus Infections ; complications ; epidemiology ; virology ; Female ; Genetic Association Studies ; Genome, Viral ; Herpesvirus 4, Human ; genetics ; isolation & purification ; Humans ; Incidence ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; epidemiology ; virology ; Neoplasm Proteins ; genetics ; Pilot Projects ; Polymorphism, Single Nucleotide ; Risk Assessment ; methods ; Tumor Cells, Cultured ; Viral Proteins ; genetics

OBJECTIVETo investigate the preventive effects of Qiangzhi Decoction (, QZD) on influenza A pneumonia through inhibition of inflammatory cytokine storm in vivo and in vitro.

METHODSOne hundred ICR mice were randomly divided into the virus control, the Tamiflu control and the QZD high-, medium-, and low-dose groups. Mice were infected intranasally with influenza virus (H1N1) at 10 median lethal dose (LD50). QZD and Tamiflu were administered intragastrically twice daily from day 0 to day 7 after infection. The virus control group was treated with distilled water alone under the same condition. The number of surviving mice was recorded daily for 14 days after viral infection. The histological damage and viral replication and the expression of inflammatory cytokines were monitored. Additionally, the suppression capacity on the secretion of regulated on activation normal T cells expressed and secreted (RANTES) and tumor necrosis factor-α (TNF-α) in epithelial and macrophage cell-lines were evaluated.

RESULTSCompared with the virus control group, the survival rate of the QZD groups significantly improved in a dose-dependent manner (P<0.05), the viral titers in lung tissue was inhibited (P<0.05), and the production of inflammatory cytokines interferon-γ (IFN-γ), interleukin-6 (IL-6), TNF-α, and intercellular adhesion molecule-1 (ICAM-1) were suppressed (P<0.05). Meanwhile, the secretion of RANTETS and TNF-α by epithelial and macrophage cell-lines was inhibited with the treatment of QZD respectively in vitro (p<0.05) CONCLUSIONS: The preventive effects of QZD on influenza virus infection might be due to its unique cytokine inhibition mechanism. QZD may have significant therapeutic potential in combination with antiviral drugs.

Animals ; Cell Line ; Cell Survival ; drug effects ; Chemokine CCL5 ; metabolism ; Chemokines ; metabolism ; Cytokines ; metabolism ; Dogs ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Hemagglutination, Viral ; drug effects ; Humans ; Inflammation ; pathology ; Influenza A Virus, H1N1 Subtype ; drug effects ; physiology ; Influenza A Virus, H1N2 Subtype ; drug effects ; Lung ; drug effects ; pathology ; Madin Darby Canine Kidney Cells ; Mice, Inbred ICR ; Orthomyxoviridae Infections ; complications ; pathology ; prevention & control ; Pneumonia ; complications ; pathology ; prevention & control ; Protective Agents ; pharmacology ; therapeutic use ; Survival Rate ; Tumor Necrosis Factor-alpha ; pharmacology

The infiltration of monocytes into the CNS represents one of the early steps to inflammatory events in AIDS-related encephalitis and dementia. Increased activity of selected matrix metalloproteinases (MMPs) such as MMP-9 impairs the integrity of blood-brain barrier leading to enhanced monocyte infiltration into the CNS. In this study, we examined the effect of HIV-1 Tat on the expression of MMP-9 in CRT-MG human astroglioma cells. Treatment of CRT-MG cells with HIV-1 Tat protein significantly increased protein levels of MMP-9, as measured by Western blot analysis, zymography and an ELISA. Treatment of CRT-MG cells with HIV-1 Tat protein markedly increased mRNA levels of MMP-9, as analyzed by RT-PCR. Pretreatment of CRT-MG cells with NF-kappaB inhibitors led to decrease in Tat-induced protein and mRNA expression of MMP-9. Pretreatment of CRT-MG cells with MAPK inhibitors suppressed Tat-induced MMP-9 expression. Furthermore, HIV-1 Tat-induced expression of MMP-9 was significantly inhibited by neutralization of TNF-alpha, but not IL-1beta and IL-6. Taken together, our results indicate that HIV-1 Tat can up-regulate expression of MMP-9 via MAPK-NF-kappaB-dependent mechanisms as well as Tat-induced TNF-alpha production in astrocytes.
AIDS Dementia Complex/*metabolism ; Astrocytes/*drug effects/enzymology ; HIV Infections/*complications ; *HIV-1 ; Humans ; Matrix Metalloproteinase 9/*genetics/immunology ; Mitogen-Activated Protein Kinase Kinases/*metabolism ; NF-kappa B/*metabolism ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/immunology/metabolism ; Up-Regulation/drug effects ; tat Gene Products, Human Immunodeficiency Virus/*metabolism

BK virus (BKV) is a subtype of papovaviridae. The latent and asymptomatic infection of BKV is common among healthy people. The incidence of BKV re-activation in renal transplant recipients ranges 10%-68%. About 1%-7% of renal transplant recipients will suffer from BKV-associated nephropathy (BKVAN), and half of them will experience graft failure. This paper summarizes the re-activation mechanism of BKV as well as the risk factors, pathology, diagnosis, and treatment of BKVAN.
BK Virus ; physiology ; Humans ; Kidney ; pathology ; virology ; Kidney Transplantation ; Polyomavirus Infections ; diagnosis ; pathology ; therapy ; Postoperative Complications ; diagnosis ; pathology ; therapy ; virology ; Risk Factors ; Tumor Virus Infections ; diagnosis ; pathology ; therapy ; Virus Activation

Reactivation of polyoma virus (BK virus) is a significant cause of morbidity in kidney transplant patients. This seemingly insignificant viral infection that affects the majority of population at a young age, once reactivated by immunosuppression, is a major factor contributing to graft loss. Screening techniques have been developed for early prediction of BK virus reactivation. These include plasma and urine assays for detection of BK virus DNA by PCR, urine cytology for detection of "decoy cells" and electron microscopy. Combining urine cytology and serology screening can be more effective for early detection of BK virus reactivation. Immunohistochemistry can be utilized as an additional tool to support the diagnosis. Once screening tests reveal a suspicious BK virus reactivation, tissue biopsy should be performed to confirm the diagnosis, rule out acute cellular rejection and plan treatment approaches. Treatment normally includes decreasing immunosuppression and the use of antiviral drug therapy. Unfortunately, disease outcome is often unfavorable and can culminate with eventual graft loss. Renal retransplantation has been performed with mixed results. As new data emerges, we will gain a better understanding of the disease caused by BK virus and respond with improved early diagnosis and treatment to preserve graft function.
Antiviral Agents/therapeutic use ; *BK Virus ; Humans ; Immunosuppression/*adverse effects ; Kidney Diseases/pathology/*virology ; *Kidney Transplantation ; Polyomavirus Infections/*complications/drug therapy/etiology ; Tumor Virus Infections/*complications/drug therapy/etiology

Although cytologic screening has considerably reduced the incidence of cervical cancer, there are some problems which remain to be solved, such as the low sensitivity of this procedure. HPV testing is fundamentally different from conventional cytologic testing, because it evaluates the HPV infection itself, the most important causative factor for cervical cancer. In this study, the roles and clinical applications of HPV testing in cervical cancer screening are examined from 3 standpoints: in primary screening, in the management of women with low-grade cytologic abnormalities, and in the follow-up after treatment of pre-invasive or early invasive lesions.
Cervix Neoplasms/*diagnosis/*virology ; DNA, Viral/analysis ; Female ; Human ; Papillomavirus Infections/complications/diagnosis ; Papillomavirus, Human/*isolation & purification ; Tumor Virus Infections/complications/diagnosis

Familial hemophagocytic lymphohistiocytosis (FHL) is a rapidly fatal illness, usually encountered in infancy, characterized by fever, hepatosplenomegaly, pancytopenia, and central nervous system involvement. Microscopic examination of tissue shows a non-malignant lymphohistiocytic infiltrate, with prominent erythrophagocytosis. FHL is an autosomal recessive hereditary disorder but may develop secondarily to other conditions such as immunosuppression, malignancies, fat overload and certain infections. We recently experienced a case of siblings developing FHL, which may be associated with EBV infection.
Case Report ; Child, Preschool ; Female ; Herpesviridae Infections/complications* ; Herpesvirus 4, Human* ; Histiocytosis, Non-Langerhans-Cell/virology* ; Histiocytosis, Non-Langerhans-Cell/genetics* ; Human ; Infant ; Male ; Tumor Virus Infections/complications*

To determine whether the dysfunction of p53 caused either by mutation of the p53 gene itself or by binding to E6 protein of oncogenic HPVs is involved in the transitional cell carcinomas (TCCs) of the bladder, we analyzed 23 TCCs of the bladder. DNA was extracted from each paraffin embedded tissue of TCCs of bladder and polymerase chain reaction (PCR)/single strand conformation polymorphism (SSCP) analysis were performed to screen mutations in p53 tumor suppressor gene, then PCR/dot blot hybridization were performed to detect infection of HPVs. We found that p53 gene mutation was found in 3 cases and oncogenic HPV infection was detected in 8 cases and thus, the overall incidence of possible p53 dysfunction was 47.8% on DNA analysis (If the results of immunohistochemistry to detect overexpression of p53 protein were included, the incidence was 60.9%). Therefore, we concluded that dysfunction of p53 plays a major role in the development of TCCs of bladder in Korean patients.
Base Sequence ; Bladder Neoplasms/*genetics/pathology/*virology ; Dyes ; Genes, Tumor Suppressor ; *Genes, p53 ; Human ; Immunohistochemistry/methods ; Molecular Probes/genetics ; Molecular Sequence Data ; *Mutation ; *Papillomavirus, Human/classification/isolation & purification ; Papovaviridae Infections/*complications ; Polymorphism, Single-Stranded Conformational ; Support, Non-U.S. Gov't ; Tumor Virus Infections/*complications