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Chinese Medical Journal 2006年第10期119卷 871-874页

作者： FAN Jun MA Wei-hang YANG Mei-fang XUE Han GAO Hai-nü LI Lan-juan Key Laboratory of Ministry Infectious Disease Institute ofInfectious Diseases First Affiliated Hospital Zhejiang UniversitySchool of Medicine Hangzhou 310003 China

cytomegalovirus （CMV） infection is a major and often deadly complication of haematopoietic stem cell （HSC） transplantation. Successful preemptive CMV therapy in transplant patients depends on the availability of sensitive, specific, and timely diagnostic tests for CMV infections. The pp65 antigenemia assay has been used for this purpose with considerable success but has disadvantages of being time-consuming and labor-intensive .

关键词： haematopoietic stem cell transplantation cytomegalovirus real-time systems polymerase chain reaction

Systemic autoimmune abnormalities complicated by cytomegalovirus-induced hemophagocytic lymphohistiocytosis:A case report

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World Journal of Clinical Cases 2020年第20期8卷 4946-4952页

作者： Shu-Xian Miao Zhi-Qi Wu Hua-Guo Xu Department of Laboratory Medicine The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029Jiangsu ProvinceChina

BACKGROUND Hemophagocytic lymphohistiocytosis(HLH)is a rare but life-threatening disorder,characterized by a hyperimmune response.The mortality is high despite progress being made in the diagnosis and treatment of the disease.HLH is traditionally divided into primary(familial or genetic)and secondary(reactive)according to the etiology.Secondary HLH(sHLH),more common in adults,is often associated with underlying conditions including severe infections,malignancies,autoimmune diseases,or other etiologies.CASE SUMMARY The case involves a 31-year-old woman,presented with a high persistent fever,rash,and splenomegaly.She met the diagnostic criteria of the HLH-2004 guideline and thus was diagnosed with HLH,with positive anti-nuclear antibody(ANA)and positive cytomegalovirus(CMV)-DNA.The patient responded well to a combination of immunomodulatory,chemotherapy,and supportive treatments.When her PCR evaluation for CMV turned negative,her serum ferritin also dropped significantly.Her clinical symptoms improved dramatically,and except for ANA,the abnormal laboratory findings associated with HLH returned to normal.Our previous study has shown that the median overall survival of HLH patients is only 6 mo;however,our patient has been cured and has not presented with any relapse of the disease for 6 years.CONCLUSION This case emphasizes that thorough early removal of the CMV infection is significant for the prognosis of this HLH patient.

关键词： Hemophagocytic lymphohistiocytosis Autoimmune abnormalities cytomegalovirus Anti-nuclear antibody Serum ferritin Case report

cytomegalovirus Infection and Coronary Heart Disease Risk:A Meta-analysis

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Cytomegalovirus Infection and Coronary Heart Disease Risk:A ...

Intrinsic host restriction factors of human cytomegalovirus replication and mechanisms of viral escape

中国微循环学会2011年全国学术会议

Background The chronic inflammatory process including cytomegalovirus（CMV） infection has been hypothesized to induce the progression of atherosclerosis in coronary heart disease（CHD）.Numbers studies were conducted to analyze the association between CMV infection and risk of CHD,but no clear consensus had been reached.Methods To assess this relationship more precisely,a meta-analysis was performed.The electronic databases PubMed,Embase,and CNKI were searched;Data were extracted and analyzed independently by two investigators.Results Ultimately,55 studies,involving 9000 cases and 8608 controls from 6 prospective studies（all with a nested case-control design）and 49 retrospective case-control studies were included.Overall,people exposed to CMV infection had an odds ratio（OR）of 1.67（95%CI,1.56-1.79）for CHD risk,relative to those not exposed.CMV infection was clearly identified as a risk factor for CHD in both prospective studies（OR,1.31;95%CI,1.132-1.517）and retrospective studies（OR,1.79;95%CI,1.659-1.939）,and in both Asian group（OR,2.69;95%CI,2.304-3.144）and Non-Asian group（OR,1.48;95%CI,1.371-1.600）.Interestingly,in the subgroup analyses by detection methods of CMV,the increased risk（OR,8.121）was greater among studies using polymerase chain reaction（PCR）than the risk（OR,1.561）among studies using enzyme-linked immunosorbent assay（ELISA）.Conclusion In conclusion,this meta-analysis suggested that CMV infection is associated with an increased risk for CHD, especially among Asian populations.

关键词： cytomegalovirus infection coronary heart disease meta-analysis

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World Journal of Virology 2016年第3期5卷 87-96页

作者： Santo Landolfo Marco De Andrea Valentina Dell'Oste Francesca Gugliesi Department of Public Health and Pediatric Sciences Laboratory of Pathogenesis of Viral InfectionsUniversity of Turin

Before a pathogen even enters a cell, intrinsic immune defenses are active. This first-line defense is mediated by a variety of constitutively expressed cell proteins collectively termed "restriction factors"(RFs), and they form a vital element of the immune response to virus infections. Over time, however, viruses have evolved in a variety ways so that they are able to overcome these RF defenses via mechanisms that are specific for each virus. This review provides a summary of the universal characteristics of RFs, and goes on to focus on the strategies employed by some of the most important RFs in their attempt to control human cytomegalovirus(HCMV) infection. This is followed by a discussion of the counter-restriction mechanisms evolved by viruses to circumvent the host cell's intrinsic immune defenses. RFs include nuclear proteins IFN-γ inducible protein 16(IFI16)(a Pyrin/HIN domain protein), Sp100, promyelocytic leukemia, and h Daxx; the latter three being the keys elements of nuclear domain 10(ND10). IFI16 inhibits the synthesis of virus DNA by downregulating UL54 transcription- a gene encoding a CMV DNA polymerase; in response, the virus antagonizes IFI16 via a process involving viral proteins UL97 and pp65(p UL83), which results in the mislocalizing of IFI16 into the cytoplasm. In contrast, viral regulatory proteins, including pp71 and IE1, seek to modify or disrupt the ND10 proteins and thus block or reverse their inhibitory effects upon virus replication. All in all, detailed knowledge of these HCMV counter-restriction mechanisms will be fundamental for the future development of new strategies for combating HCMV infection and for identifying novel therapeutic agents.

关键词： Human cytomegalovirus Intrinsic immunity Restriction factors Viral escape mechanisms DNA sensors

Preparation and Characterization of HLA-A*0201 Tetramer Loaded with IE-1_(316-324) Antigenic Peptide of Human cytomegalovirus

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Cellular & Molecular Immunology 2006年第5期3卷 367-371页

作者： Lihui Xu Qingbing Zha Hong Sun Qiantao Jia Fengyao Li Xianhui He Institute of Tissue Transplantation and Immunology College of Life Science and Technology Jinan University Guangzhou 510632 China Institute of Bioengineering College of Life Science and Technology Jinan University Guangzhou 510632 China Clinical Experimental Center of the First Affiliated Hospital linan University Guangzhou 510632 China Institute of Tissue Transplantation and Immunology College of Life Science and Technology Jinan University 601 Huangpu Dadao West Guangzhou 510632 China

Major histocompatibility complex （MHC） class I tetramer technology has become the central technique for analyzing antigen-specific CD8^＋ T cell responses and it has been widely used to explore the differentiation and formation of memory CD8^＋ T cells. Previously, a simplified and efficient procedure for preparing high quality HLA-A＊0201 tetramers has been established in our lab and the tetramers loaded with HCMV peptide pp6549s.50a has been successfully applied to investigate HCMV-specific CD8^＋ T cells in Chinese populations. Using similar procedure we reported here the construction of HLA-A＊0201 tetramer loaded with another dominant epitope derived from immediate early （IE）-1 316.324 （VLEETSVML, VLE） of HCMV （A2-VLE） and characterization of this tetramer. After A2-VLE monomer was prepared and purified, its tetramer was then formed at a yield of 83%. The optimized amount of A2-VLE tetramer for staining 100 μl whole blood was 0.5 μg with incubation at 4℃ for 1 h. Furthermore, the dissociation constant of the tetramer binding to the specific CD8^＋ T cells of one HLA-A2^＋ donor was estimated to be 32.7 nmol/L, which is markedly higher than that of MHC monomer. The construction of A2-VLE tetramer provides an alternative choice for investigating HCMV-specific CD8^＋ T cell responses and will deepen our understanding of the differentiation and formation of HCMV-specific memory CD8^＋ T cells. Cellular ＆ Molecular Immunology.

关键词： HLA tetramer cytomegalovirus immediate early-1 dissociation constant

cytomegalovirus infection in liver transplant recipients

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Hepatobiliary & Pancreatic Diseases International 2002年第1期1卷 30-32页

作者： Jun Fan Wei-Hang Ma Jing Qian Zhi Chen Dong--Sheng Huang Wei-Lin Wang Shu-Sen Zheng From the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China First Affiliated Hospital Zhejiang University Sch. of Medicine Hangzhou 310003 China

Objective: To explore cytomegalovirus （CMV） infec-tion in recipients of liver transplantation （LT）.Methods: 30 recipients of LT were screened for theappearance of CMV infection by using ELISA to testanti-CMV-Ab from serum samples and using im-munohistochemistry method to test CMV antigen ex-pression and nested-PCR to amplify CMV-DNA fromblood samples.Results: Four of 243 samples taken from 30 recipientscame out positive of anti-CMV IgC; and anti-CMVIgM with a positive rate of 100% and 1.6% respec-tively. 85 samples resulted in CMV antigen expression（35.0%） with the average antigen index being 4.2±3.1/5×10;WBC. Besides, 99 samples were found tobe positive by nested-PCR with a positive rate of40.7%. 61 samples were found to be simultaneously pos-itive in test of CMV antigen and DNA, with a rate of25.1%.Conclusions: Infection of CMV is common in recipi-ents of LT. Simultaneous screening of anti-CMV-Ab, CMV-Ag and CMV-DNA after liver transplanta-tion is very important for early diagnosis of CMV in-fection.

关键词： cytomegalovirus anti-CMV-Ab cytomegalovirus antigen cytomegalovirus DNA liver transplantation

Human cytomegalovirus-encoded US28 may act as a tumor promoter in colorectal cancer

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World Journal of Gastroenterology 2016年第9期22卷 2789-2798页

作者： Zhen-Zhai Cai Jian-Gang Xu Yu-Hui Zhou Ji-Hang Zheng Ke-Zhi Lin Shu-Zhi Zheng Meng-Si Ye Yun He Chang-Bao Liu Zhan-Xiong Xue Department of Gastroenterology The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University Department of Surgical Oncology Wenzhou Central Hospital Department of General Surgery The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University Department of Pathology Wenzhou Medical University

AIM: To assess human cytomegalovirus-encoded US28 gene function in colorectal cancer(CRC) pathogenesis.METHODS: Immunohistochemical analysis was performed to determine US28 expression in 103 CRC patient samples and 98 corresponding adjacent noncancerous samples. Patient data were compared by age, sex, tumor location, histological grade, Dukes' stage, and overall mean survival time. In addition, the US28 gene was transiently transfected into the CRC LOVO cell line, and cell proliferation was assessed using a cell counting kit-8 assay. Cell cycle analysis by flow cytometry and a cell invasion transwell assay were also carried out.RESULTS: US28 levels were clearly higher in CRC tissues(38.8%) than in adjacent noncancerous samples(7.1%)(P = 0.000). Interestingly, elevated US28 amounts in CRC tissues were significantly associated with histological grade, metastasis, Dukes' stage, and overall survival(all P < 0.05); meanwhile, US28 expression was not significantly correlated with age, sex or tumor location. In addition, multivariate Coxregression data revealed US28 level as an independent CRC prognostic marker(P = 0.000). LOVO cells successfully transfected with the US28 gene exhibited higher viability, greater chemotherapy resistance, accelerated cell cycle progression, and increased invasion ability.CONCLUSION: US28 expression is predictive of poor prognosis and may promote CRC.

关键词： Human cytomegalovirus US28 Colorectal cancer Prognosis Proliferation Invasion

Two strategies for prevention of cytomegalovirus infections after liver transplantation

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World Journal of Gastroenterology 2016年第12期22卷 3412-3417页

作者： Philipp Simon Max Sasse Sven Laudi David Petroff Michael Bartels Udo X Kaisers Sven Bercker Department of Anesthesia and Intensive Care Medicine Medical Faculty University of Leipzig Clinical Trial Centre Leipzig University of Leipzig Department of Visceral Transplantation Vascular and Thoracic Surgery Medical Faculty University of Leipzig

AIM: To analyze differences in patients' clinical course, we compared two regimes of either preemptive therapy or prophylaxis after liver transplantation.METHODS: This retrospective study was reviewed and approved by the institutional review board of the University of Leipzig. cytomegalovirus(CMV) prophylaxis with valganciclovir hydrochloride for liver transplant recipients was replaced by a preemptive strategy in October 2009. We retrospectively compared liver transplant recipients 2 years before and after October 2009. During the first period, all patients received valganciclovir daily. During the second period all patients included in the analysis were treated following a preemptive strategy. Outcomes included one year survival and therapeutic intervention due to CMV viremia or infection.RESULTS: Between 2007 and 2010 n = 226 patients underwent liver transplantation in our center. n = 55 patients were D^+/R^- high risk recipients and were excluded from further analysis. A further 43 patients had to be excluded since CMV prophylaxis/preemptive strategy was not followed although there was no clinical reason for the deviation. Of the remaining 128 patients whose data were analyzed, 60 receivedprophylaxis and 68 were treated following a preemptive strategy. The difference in overall mortality was not significant, nor was it significant for one-year mortality where it was 10%(95%CI: 8%-28%, P = 0.31) higher for the preemptive group. No significant differences in blood count abnormalities or the incidence of sepsis and infections were observed other than CMV. In total, 19 patients(14.7%) received ganciclovir due to CMV viremia and/or infections. Patients who were treated according to the preemptive algorithm had a significantly higher rate risk of therapeutic intervention with ganciclovir [n = 16(23.5%) vs n = 3(4.9%), P = 0.003)].CONCLUSION: These data suggest that CMV prophylaxis is superior to a preemptive strategy in patients undergoing liver transplantation.

关键词： Transplantation Liver cytomegalovirus Preemptive Prophylaxis Valganciclovir Therapy

Acute pancreatitis with cytomegalovirus infection in a kidney transplant recipient: A case report

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Journal of Acute Disease 2019年第1期8卷 43-44页

作者： Zeinab Mohseni Afshar Arefeh Babazadeh Soheil Ebrahimpour Sima Golmohammadi Department of Infectious Diseases Faculty of MedicineKermanshah University of Medical SciencesKermanshahIran Infectious Diseases and Tropical Medicine Research Center Health Research InstituteBabol University of Medical SciencesBabolI.R.Iran Department of Internal Medicine Kermanshah University of Medical SciencesKermanshahIran

cytomegalovirus (CMV) can cause significant inflammation. Besides, it is an important cause of pancreatitis in organ transplantations. We report a case of CMV pancreatitis in a 48-year-old male kidney transplant recipient who was admitted with elevated amylase (3337 U/L) and lipase (1160 U/L) enzymes, and abdominal pain. CMV infection was tested by reverse transcription polymerase chain reaction and the result was positive. CMV viremia was successfully cleared with ganciclovir. Then the absence of some of more noticeable clinical symptoms of pancreatitis may not be a decisive reason not to rule out the disease in transplanted cases.

关键词： cytomegalovirus Acute pancreatitis Kidney transplant recipient

Protein interactions in the murine cytomegalovirus capsid revealed by cryoEM

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Protein & Cell 2013年第11期4卷 833-845页

作者： Wong HHui Qiyi Tang Hongrong Liu Ivo Atanasov Fenyong Liu Hua Zhu ZHong Zhou The California NanoSystems Institute(CNSI) University of CaliforniaLos Angeles(UCLA)Los AngelesCA 90095USA Department of Microbiology Immunology and Molecular GeneticsUCLALos AngelesCA 90095USA D epartment of Microbiology/AIDS program Ponce School of Medicine395 Zona IndustrialReparadara-2PoncePR 00716USA School of Public Health University of California at BerkeleyBerkeleyCA 94720USA Department of Microbiology and Molecular Genetics International Center for Public Health(or ICPH)Room E350D225 Warren StreetUMDNJ-New Jersey Medical SchoolNewarkNJ 07103USA Current address:College of Physics and Information Science Hunan Normal UniversityChangsha 410081China

cytomegalovirus(CMV)is distinct among members of the Herpesviridae family for having the largest dsDNA genome(230 kb).Packaging of large dsDNA genome is known to give rise to a highly pressurized viral capsid,but molecular interactions conducive to the formation of CMV capsid resistant to pressurization have not been described.Here,we report a cryo electron microscopy(cryoEM)structure of the murine cytomegalovirus(MCMV)capsid at a 9.1Åresolution and describe the molecular interactions among the~3000 protein molecules in the MCMV capsid at the secondary structure level.Secondary structural elements are resolved to provide landmarks for correlating with results from sequence-based prediction and for structure-based homology modeling.The major capsid protein(MCP)upper domain(MCPud)containsα-helices andβ-sheets conserved with those in MCPud of herpes simplex virus type 1(HSV-1),with the largest differences identifi ed as a“saddle loop”region,located at the tip of MCPud and involved in interaction with the smallest capsid protein(SCP).Interactions among the bacteriophage HK97-like fl oor domain of MCP,the middle domain of MCP,the hook and clamp domains of the triplex proteins(hoop and clamp domains of TRI-1 and clamp domain of TRI-2)contribute to the formation of a mature capsid.These results offer a framework for understanding how cytomegalovirus uses various secondary structural elements of its capsid proteins to build a robust capsid for packaging its large dsDNA genome inside and for attach-ing unique functional tegument proteins outside.

关键词： cytomegalovirus herpes simplex virus type 1 cryo electron microscopy three-dimensional major capsid protein