The human cytomegalovirus (HCMV) is a widespread herpesvirus. Virus reactivation from latency can lead to stillbirth, miscarriage, fetal anomalies, and intrauterine growth retardation. During latent infection with the HCMV, the virus can be cleared by the immune response or apoptosis of host cells. However, the HCMV has developed several strategies to manipulate expression of its genes and the microenvironment of host cells. Recent studies have shown that latent infection with the HCMV is associated with viral: regulation of early expression of genes; evasion of cell death; evasion of the immune response; regulatin of non-coding RNAs. This review summarizes recent research progress on the mechanisms underpinning latent infection with the HCMV.
Animals ; Cytomegalovirus ; genetics ; physiology ; Cytomegalovirus Infections ; immunology ; virology ; Humans ; Viral Proteins ; genetics ; metabolism ; Virus Latency

Cytomegalovirus (CMV) reactivation in immune compromised patients such as those undergoing hematopoietic progenitor cell transplantation (HPCT) and those with HIV infections can cause severe morbidity and mortality despite treatment with appropriate antiviral agents. The recovery of Cytomegalovirus (CMV) specific cytotoxic T lymphocytes (CTL) plays an important role in the reconstitution of CMV specific immunity in immunocompromised patients. Recent studies have reported that CMV reactivation can be successfully treated by adoptive transfer of CMV-specific T cell clones from CMV seropositive donors expanded in vitro with CMV infected fibroblasts or lysates of CMV infected cells. Other studies have used immune dominant CMV proteins or peptides to expand CMV-specific cytotoxic T lymphocytes. This review describes the clinical manifestations of CMV disease in immunocompromised patients, recent advances of antiviral therapy for CMV disease, the principals of the induction of cellular immune response to CMV, and the clinical application of CMV immunotherapy.
Cytomegalovirus Infections/*immunology/*therapy ; Humans ; *Immunocompromised Host ; *Immunotherapy, Adoptive

BACKGROUNDTo develop a capturing-ELISA for the detection of anti-HCMV-IgM antibody in serum.

METHODSThe anti-HCMV-IgM antibody was detected in 68 patients with HCMV infection by the capturing-ELISA, and the results were compared with those of indirect ELISA.

RESULTSThe specificity and sensitivity of the capturing-ELISA were shown to be significantly higher than those of indirect ELISA, and its results were not affected by RF factor.

CONCLUSIONThe capturing ELISA is specific, sensitive, convenient and reliable method which may be feasible for clinical use.

Antibodies, Viral ; blood ; Cytomegalovirus ; immunology ; Cytomegalovirus Infections ; immunology ; virology ; Enzyme-Linked Immunosorbent Assay ; methods ; Humans ; Immunoglobulin M ; blood

Human cytomegalovirus (HCMV) is an ubiquitous pathogen that infects a majority of the world's population. The virus can establish lifelong infection once the human body is infected by HCMV and virus can be reactivated from a latent state in immune suppressed individuals. HCMV has developed several strategies to evade host immune surveillance after millions of years of co-evolution with mankind. One of the classical tricks is encoding homologous to human immune factors or stealing host cellular genes that have significant functions in immune system. Virus encoded immune modulators which participate in regulating the major histocompatibility complex, cellular immunity, humoral immunity, cytokines and chemokines are supposed to play a significant role in the pathogenesis of HCMV. Evaluation of "mutually assured survival" relationship between virus and host provides important insights into viral immunopathogenesis and study of viral immunomodulatory proteins might help us to uncover new human genes that control immunity.
Animals ; Chemokines ; physiology ; Cytokines ; physiology ; Cytomegalovirus ; pathogenicity ; Cytomegalovirus Infections ; immunology ; Game Theory ; Humans ; Immunity, Humoral ; Killer Cells, Natural ; immunology

BACKGROUNDCloning recombinant human Fab fragment against HCMV for the purpose of prophylaxis and control of HCMV infection.

METHODSThe authors constructed a HCMV phage display library with 2 x 10(6) clones, then used purified HCMV viral lysates to pan the library, then screened by ELISA.

RESULTSThree clones showed positive responses in ELISA, they also showed high specificity in IFA, two of them could neutralize HCMV in neutralizing assays.

CONCLUSIONThe specific binding of Fab antibodies to HCMV was demonstrated by ELISA, IFA and neutralizing activities. These results provide us the basis for further research of neutralizing recombinant human whole IgG molecule.

Antibodies, Viral ; genetics ; immunology ; Cytomegalovirus ; genetics ; immunology ; Cytomegalovirus Infections ; immunology ; virology ; Escherichia coli ; genetics ; metabolism ; Gene Expression ; Humans ; Immunoglobulin Fab Fragments ; genetics ; immunology ; Neutralization Tests ; Peptide Library

OBJECTIVETo investigate the effect of HCMV infection on the expression of interleukin-8 (IL-8) and regulated on activation, normal T expressed and secreted (RANTES) so as to explore the possible mechanism of the immune-pathological changes caused by HCMV infection.

METHODSExpression of both IL-8 and RANTES mRNA was detected by RT-PCR. Secretion of IL-8 and RANTES protein was quantitated by enzyme linked immune-sororbant assay (ELISA).

RESULTSAfter HCMV infection, the expression of IL-8 in HEL cells was found to be increased gradually concomitant with the prolonged infection time at both the transcriptional level and the protein level. By the time of 72 h.p.i, as compared with mock-infected cells, IL-8 mRNA expression was increased up to 12-fold and IL-8 protein up to 9-fold in HCMV-infected cells. The expression of RANTES mRNA was occurred at 8 h.p.i, with a maximum at 24 h.p.i, since then it remained relatively high level. The expression of RANTES protein peaked at 24 h.p.i, then dropped sharply and was almost undetectable by the time at 72 h.p.i.

CONCLUSIONHCMV infection of HEL cells may induce the transcription of IL-8 gene as well as the production of IL-8 orotein. HCMV may down-regulate extra-cellular production of RANTES protein.

Cells, Cultured ; Chemokines ; genetics ; immunology ; Cytomegalovirus ; physiology ; Cytomegalovirus Infections ; genetics ; immunology ; virology ; Female ; Fibroblasts ; immunology ; virology ; Gene Expression ; Humans ; Pilot Projects ; Pregnancy

BACKGROUNDTo search for the serological findings and early clinical manifestations as evidences for prevention and treatment TORCH infections in pregnant women and newborns as early as possible.

METHODSELASA was performed to screen specific anti-TORCH (Toxoplasma gondii, Cytomegalovirus, Rubella virus, Herpes simplex virus) Ig-M antibodies.

RESULTSTotally 1,554 in-patients who were treated in Neonatal Intensive Care Unit (NICU) of our hospital from January 2000 to January 2003 were retrospectively studied, 48 of them had TORCH infections. Cytomegalovirus (CMV), rubella and herpes simplex virus infections accounted for 52.1%, 33.3% and 14.6%, respectively. None of them had toxoplasma infection.

CONCLUSIONTORCH infections can cause multiorgan lesions, such as hearing impairment, hyperbilirubinemias and liver dysfunction, impairment of neurologic system, myocardial impairment, thrombocytopenia, and congenital heart disease.Rubella vaccine inoculation, serological screening during pregnancy and early period of newborn, intervention and treatment in the early period are most important.

Antibodies, Viral ; blood ; immunology ; Cytomegalovirus Infections ; immunology ; Female ; Herpes Simplex ; immunology ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases ; immunology ; virology ; Male ; Neonatal Screening ; Retrospective Studies ; Rubella ; immunology ; Toxoplasmosis ; immunology

OBJECTIVETo further study the role of human cytomegalovirus (HCMV) infection in the pathogenesis of the type 2 diabetes mellitus.

METHODSHCMV DNA levels in sera from 29 type 2 diabetic patients and 23 controls were measured by quantitative polymerase chain reaction (PCR), and comparative analyses was made between HCMV DNA and T cell subsets, blood glucose (BG), insulin (Ins) and C peptide (C-P).

RESULTSThe levels of HCMV DNA were (1.81+/-1.67) x 10(8) copies/ml for type 2 diabetic patients, a level significantly higher than that (5.50+/-4.30) x 10(7) copies/ml of controls. The percentage of CD8 for type 2 diabetic patients with positive HCMV DNA was 29.53%+/-2.00%, being much higher than that for controls (27.13%+/-4.12%), while the ratio of CD4/CD8 1.24+/-0.05 was significantly lower than that 1.41+/-0.10 of controls. Fasting C-P of type 2 diabetic patients with positive HCMV DNA was far lower than that of those with negative HCMV DNA, but the differences of BG and Ins between the two groups were not significant.

CONCLUSIONActive HCMV infection of type 2 diabetic patients may suppress cellular immunity and its influence on the pathogenesis of the type 2 diabetes mellitus should be further studied.

Adult ; Cytomegalovirus ; genetics ; Cytomegalovirus Infections ; complications ; immunology ; DNA, Viral ; blood ; Diabetes Mellitus, Type 2 ; immunology ; virology ; Female ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; T-Lymphocyte Subsets

OBJECTIVETo provide experimental evidence for development of human cytomegalovirus (HCMV) nucleic acid vaccine, HCMV surface protein (gB), membrane protein (pp150), and gB-pp150 fused gene eukaryotic expression vector were constructed.

METHODSgB and pp150 genes were amplified and fused into gB-pp150, then were cloned into pcDNA 3.1 (+) to obtain recombinant expression plasmids pcDNA 3.1 (+) -gB, pcDNA 3.1 (+) -pp150 and pcDNA 3.1 (+) -gB-pp150, which were encapsulated with chitosan. Mouse were vaccinated and the humoral and cell immune response were determined by ELISA, specific proliferative response of plenic lymphocytes.

RESULTSThe gB, pp150 and gB-pp150 fusion gene eukaryotic expression vector were successfully constructed. The antibodies A value induced by pcDNA3.1(+) -gB or pcDNA3.1 (+) -gB-pp150 were much higher than that of pcDNA3.1 (+) (P < 0.01). The IFN-gamma levels induced by pcDNA3.1 (+) -pp150 and pcDNA3.1 (+) -gB-pp150 were significantly higher than that of pcDNA3.1 (+). There are significant diference between the stimulating indexes of pcDNA3.1(+) -pp150 or pcDNA3.1 (+) -gB-pp150 immunized and normal mice.

CONCLUSIONThe DNA vaccine pcDNA3.1 (+) -gB can induce significant humoral immunity response, and pcDNA3.1 (+) -pp150 can induce high cellular immune response, whereas pcDNA3.1 (+) -gB-pp150 can induce both humoral and cellar immune responses in BALB/c mice.

Animals ; Cytomegalovirus ; genetics ; immunology ; Humans ; Immunity, Cellular ; immunology ; Immunization ; Mice ; Mice, Inbred BALB C ; Recombinant Fusion Proteins ; immunology ; Vaccination ; Vaccines, DNA ; immunology ; Viral Envelope Proteins ; immunology

BACKGROUNDTo study the composition and significance of the inclusion bodies of human cytomegalovirus (HCMV).

METHODSMicrodissection of inclusion bodies, PCR and Southern blot were adopted to detect DNA, and immunohistochemistry method and catalyzed signal amplification (CSA) were used to detect the different antigens of HCMV.

RESULTSThe inclusion bodies of HCMV were separated from the tissue section of human salivary gland. The fragments amplified by PCR from these dissected inclusion bodies were confirmed to be the DNA of HCMV. With the immunohistochemical method CSA, the immediately early and early antigens of HCMV were detected with monoclonal antibodies DDG9/CCH2, while matrix protein AAC10 was negative in the inclusion bodies.

CONCLUSIONThe ingredient of inclusion bodies of HCMV included the DNA and the antigens expressed in specific stage of the virus.

Antigens, Viral ; analysis ; immunology ; Cytomegalovirus ; genetics ; immunology ; Cytomegalovirus Infections ; diagnosis ; immunology ; virology ; DNA, Viral ; analysis ; genetics ; Humans ; Immunohistochemistry ; Inclusion Bodies ; chemistry ; immunology ; virology ; Microdissection ; Salivary Glands ; chemistry ; immunology ; virology