Influence Of Human Cytomegalovirus Infection Research Articles

Impact of HCMV Infection on NK Cell Development and Function after HSCT

Natural Killer (NK) cell function is regulated by an array of inhibitory and activating surface receptors that during NK cell differentiation, at variance with T and B cells, do not require genetic rearrangement. Importantly, NK cells are the first lymphocyte population recovering after hematopoietic stem cell transplantation (HSCT). Thus, their role in early immunity after HSCT is considered crucial, as they can importantly contribute to protect the host from tumor recurrence and viral infections before T-cell immunity is fully recovered. In order to acquire effector functions and regulatory receptors, NK cell precursors undergo a maturation process that can be analyzed during immune reconstitution after HSCT. In this context, the occurrence of human cytomegalovirus (HCMV) infection/reactivation was shown to accelerate NK cell maturation by promoting the differentiation of high frequencies of NK cells characterized by a KIR+NKG2A− and NKG2C+ mature phenotype. Thus, it appears that the development of NK cells and the distribution of NK cell receptors can be deeply influenced by HCMV infection. Moreover, in HCMV-infected subjects the emergence of so called “memory-like” or “long-lived” NK cells has been documented. These cells could play an important role in protecting from infections and maybe from relapse in patients transplanted for leukemia. All the aspects regarding the influence of HCMV infection on NK cell development will be discussed.

Influence of human cytomegalovirus infection on cholesterol metabolism in smooth muscle cells of umbilical arteries and the related mechanisms

Objective To investigate the effect of human cytomegalovirus(HCMV) infection on cholesterol metabolism in smooth muscle cells of the umbilical arteries and the related mechanisms.Methods Vascular smooth muscle cells were isolated from umbilical arteries and were challenged with 1 MOI HCMV,and the intercellular content of cholesterol was determined.Cells treated with DMEM/F12 solution containing 3% fetal bovine serum were taken as mock infection controls.The differentially expressed genes were screened by cDNA microarray in each group,and the abnormally expressed genes associated with cholesterol metabolism were identified by fluorescence quantitative RT-PCR.Results The intracellular content of cholesterol([0.71±0.06] μmol/10~6 cells) was significantly higher in HCMV infection group at 72 h after infection compared with that in the control group(t=7.950,P=0.000 2).cDNA microarray and fluorescence quantitative RT-PCR showed that the expressions of HMG-CoA synthetase and HMG-CoA reductase were greatly up-regulated compared with those in the mock infection group 48 and 72 h after infection(P0.01).Conclusion Human cytomegalovirus infection can increase the synthesis of cholesterol through up-regulating cholesterol metabolism-associated genes in vascular smooth muscle cells,leading to unbalancd cholesterol metabolism.

Correction: Influence of human cytomegalovirus infection on the NK cell receptor repertoire in children

Correction: Influence of human cytomegalovirus infection on the NK cell receptor repertoire in children

Influence of human cytomegalovirus infection on the NK cell receptor repertoire in children

Human cytomegalovirus (hCMV) infection is usually asymptomatic but may cause disease in immunocompromised hosts. It has been reported that hCMV infection may shape the NK cell receptor (NKR) repertoire in adult individuals, promoting a variable expansion of the CD94/NKG2C+ NK cell subset. We explored the possible relationship between this viral infection and the expression pattern of different NKR including CD94/NKG2C, CD94/NKG2A, immunoglobulin-like transcript 2 (ILT2, CD85j), KIR2DL1/2DS1, KIR3DL1, and CD161 in peripheral blood lymphocytes from healthy children, seropositive (n=21) and seronegative (n=20) for hCMV. Consistent with previous observations in adults, a positive serology for hCMV was associated with increased numbers of NKG2C+ NK and T cells as well as with ILT2+ T lymphocytes. Moreover, the proportions of CD161+ and NKG2C+CD56-CD3- NK cells also tended to be increased in hCMV+ individuals. Excretion of the virus was associated with higher proportions of NKG2C+ NK cells. Altogether, these data reveal that hCMV may have a profound influence on the NKR repertoire in early childhood.

Effects of human cytomegalovirus infection on apoptosis and expression of apoptosis-regulating factors

The present study aimed to find out dynamic changes of apoptosis in human cytomegalovirus (HCMV) infected cells and the influence of HCMV infection on activation of caspase-3 and the expression of apoptosis-regulating genes, bcl-2 and fas mRNA. The sequential changes of apoptotic cell rate in high and low MOI (MOI = 2.5 and 0.25 respectively) of HCMV infected human embryonic lung fibroblasts (HELFs) at 1 h, 12 h, 24 h, 36 h, 48 h, 72 h and 96 h post-infection were measured by flow cytometry. The expression levels of caspase-3 protein and bcl-2 and fas mRNA in HCMV infected cells (MOI = 0.25) at 72 h post-infection were detected by Western blot and in situ hybridization methods, respectively. It was found that the ratio of apoptotic cells in normal controls was consistently lower, but the rates in low and high MOI infected cells were gradually increased with time prolonged, reached peak at 96 h (8.85%) and 72 h (25.63%), respectively. By Western blot analysis, only a narrow band of 32 kD (1 kD = 0.992 1 ku) procaspase-3 was found in normal cells, but a wider procaspase-3 band and a much wider band of 17 kD proteins (p17) appeared in the infected cells. Meanwhile, the expression of bcl-2 mRNA was higher and that of fas mRNA was lower in the normal HELF cells, whereas there were significantly lower bcl-2 mRNA and higher fas mRNA expression levels in HCMV infected cells. It was concluded that HCMV was a stronger inducer of apoptosis in HELF cells. Caspase-3, as the marker of undergoing apoptosis, was expressed increasingly and activated in the infected cells, indicating its action in HCMV-inducing apoptosis. Down-regulating bcl-2 mRNA expression and up-regulating fas mRNA expression were also involved in the mechanism of HCMV-induced apoptosis.

Effects of human cytomegalovirus infection on the coagulation system

Pathophysiological mechanisms of acute vascular thrombosis are not fully understood. It has been suggested that different infectious pathogens are responsible agents of thrombotic disorders. The infection hypothesis is supported by an increasing number of reports on the interaction between acute infection and coagulation. Cytomegalovirus (CMV) is supposed to play an important role in apparently unprovoked thrombosis. We reviewed all human in vitro and in vivo studies on the influence of human CMV infection on the coagulation system, as well as all case reports of acute thrombosis during acute human CMV infection. In the published literature there is mounting evidence that human CMV may play a role in thrombotic disorders. Definitive conclusions, however, cannot be drawn, although the in vitro studies are convincing and offer insight in the pathogenesis.

Cytomegalovirus infection decreases expression of thrombospondin-1 and -2 in cultured human retinal glial cells: effects of antiviral agents.

In fibroblasts, infection with human cytomegalovirus (HCMV) inhibits expression of the extracellular matrix proteins thrombospondin-1 and -2 (TSP-1 and TSP-2). These effects may depend on expression of HCMV immediate-early (IE) genes, which are activated by cellular transcription factor NF-kappaB. The influence of HCMV infection on TSP-1 and TSP-2 expression and the ability of different antiviral drugs to prevent these cellular changes in permissive cultures of human retinal glial cells were observed. Ganciclovir inhibited only HCMV late antigen (LA) expression, whereas antisense oligonucleotide ISIS 2922 and peptide SN50, inhibitors of HCMV IE expression and NF-kappaB activity, respectively, inhibited both IE and LA expression. ISIS 2922 and SN50, but not ganciclovir, prevented down-modulation of TSP-1 and TSP-2. The results showed that HCMV-induced down-modulation of TSP-1 and TSP-2 in retinal glial cells is prevented by inhibition of HCMV IE expression. These findings may be relevant to pathogenesis and treatment of HCMV retinitis.