Disseminated cytomegalovirus infection. Molecular analysis of virus and leukocyte interactions in viremia.

Saltzman, Robin; Quirk, Mary; Jordan, M. Colin

doi:10.1172/jci113313

Cited by 114 publications

(70 citation statements)

References 33 publications

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“…However, in viraemic patients with different levels of viraemia the ratio of ep65-positive to ep65-negative cells was found to be I : I00 to 1 : 100000 for PMNL, and only 1:10000 to 1:100000 for MNL. These data agree with those obtained using different hybridization techniques to detect viral nucleic acids in leukocyte subpopulations (Saltzman et al, 1988;Dankner et al, 1990).…”

supporting

confidence: 91%

Nuclear expression of the lower matrix protein of human cytomegalovirus in peripheral blood leukocytes of immunocompromised viraemic patients

Revello

Percivalle

Matteo

et al. 1992

Journal of General Virology

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supporting

confidence: 91%

Nuclear expression of the lower matrix protein of human cytomegalovirus in peripheral blood leukocytes of immunocompromised viraemic patients

Revello

Percivalle

Matteo

et al. 1992

Journal of General Virology

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“…Detection of HCMV in the PMNL fraction of peripheral blood has been reported in patients infected with human immunodeficiency virus (HIV), other immunocompromised patients and immunocompetent patients acutely ill with HCMV (Saltzman et al, 1988;Dankner et al, 1990;Fiala et al, 1975;Rinaldo et al, 1977;Revello et al, 1992;Gerna et al, 1991). Consequently, we were interested in determining whether the granulocyte might also represent a normal site of persistence which would be consistent with the clinical observations that HCMV is present in PMNL of viraemic patients.…”

mentioning

confidence: 77%

Polymorphonuclear cells are not sites of persistence of human cytomegalovirus in healthy individuals

Taylor‐Wiedeman

Hayhurst

Sissons

et al. 1993

Journal of General Virology

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Polymorphonuclear leukocytes (PMNL) have been shown to harbour human cytomegalovirus (HCMV) in viraemic patients, but to date PMNL of asymptomatic healthy subjects have not been examined directly to determine whether this is a normal site of HCMV persistence. Using the polymerase chain reaction (PCR), paired DNA samples prepared from adherent peripheral blood mononuclear cells (PBMC), which are known to be a site of persistence of HCMV, and PMNL of 10 healthy adults were analysed. All of seven individuals who were HCMV seropositive, and one of three who were seronegative gave a reproducible signal for HCMV DNA in their adherent PBMC, whereas none of the paired PMNL DNA samples gave a positive result. The remaining two seronegative subjects showed no HCMV DNA in either the PBMC or PMNL samples. In every case where PCR for HCMV was negative, PCR amplification of a control human gene was used to show there was no inability to amplify the DNA. We conclude that within the leukocyte population of normal asymptomatic HCMV carders, PMNL do not appear to harbour persistent HCMV whereas adherent PBMC in the same subjects are a site of persistence.We and others have previously used the polymerase chain reaction (PCR) to demonstrate the presence of human cytomegalovirus (HCMV) in leukocytes of seropositive and some seronegative healthy carriers (Taylor-Wiedeman et al., 1991; Stainer et al., 1989). In these normal subjects, peripheral blood monocytes (PBMC) were the principal site of persistence (TaylorWiedeman et al., 1991). However, only PBMC were studied and analysis of polymorphonuclear leukocytes (PMNL) from healthy carriers was not addressed.Detection of HCMV in the PMNL fraction of peripheral blood has been reported in patients infected with human immunodeficiency virus (HIV), other immunocompromised patients and immunocompetent patients acutely ill with HCMV (Saltzman et al., 1988;Dankner et al., 1990;Fiala et al., 1975;Rinaldo et al., 1977; Revello et al., 1992;Gerna et al., 1991). Consequently, we were interested in determining whether the granulocyte might also represent a normal site of persistence which would be consistent with the clinical observations that HCMV is present in PMNL of viraemic patients. To determine this, DNA from PMNL cells and adherent PBMC from the same blood sample for each of 10 healthy subjects was prepared and examined by PCR. In this report we show that PMNL are not a source of persistent virus in the leukocyte population of normal asymptomatic HCMV carriers.Subjects were all healthy adult volunteers whose serological status was determined using a competitive ELISA (CompEnz-CMV, Northumbria Biologicals). One subject's serum gave a negative result in ELISA but DNA from adherent PBMC was PCR-positive. A second serum sample, examined 2 months later using an HCMV latex agglutination assay (Becton Dickinson), showed the individual to have remained seronegative. Lymphoprep (Nycomed) gradient separations yielded PBMC, banding at the plasma interface, and PMNLenriched fractions lying at the top ...

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“…We chose to use macrophages for the in vitro studies for two reasons: firstly, macrophages play an important role during MCMV infections (35)(36)(37)(38), and secondly, the ability of MCMV to replicate in macrophages has been correlated with its in vivo virulence (39 -41). IFN-␤ pretreatment can inhibit MCMV replication in vitro in fibroblasts and macrophages (42,43), although the effect is relatively modest.…”

Section: Tyk2 Is Required For Control Of MCMV Replication In Macrophagesmentioning

confidence: 99%

Novel Functions of Tyrosine Kinase 2 in the Antiviral Defense against Murine Cytomegalovirus

Strobl

Bubić

Bruns

et al. 2005

The Journal of Immunology

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We have recently reported that tyrosine kinase 2 (Tyk2)-deficient mice have a selective defect in the in vivo defense against certain viruses. In our current study we show that Tyk2 is essential for the defense against murine CMV (MCMV). In vivo challenges with MCMV revealed impaired clearance of virus from organs and decreased survival of mice in the absence of Tyk2. Our in vitro studies demonstrate that MCMV replicates to dramatically higher titers in Tyk2-deficient macrophages compared with wild-type cells. We show an essential role of type I IFN (IFN-αβ) in the control of MCMV replication, with a prominent role of IFN-β. MCMV infection leads to the activation of STAT1 and STAT2 in an IFN-αβ receptor 1-dependent manner. Consistent with the role of Tyk2 in IFN-αβ signaling, activation of STAT1 and STAT2 is reduced in Tyk2-deficient cells. However, lack of Tyk2 results in impaired MCMV-mediated gene induction of only a subset of MCMV-induced IFN-αβ-responsive genes. Taken together, our data demonstrate a requirement for Tyk2 in the in vitro and in vivo antiviral defense against MCMV infection. In addition to the established role of Tyk2 as an amplifier of Jak/Stat signaling upon IFN-αβ stimulation, we provide evidence for a novel role of Tyk2 as a modifier of host responses.

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Disseminated cytomegalovirus infection. Molecular analysis of virus and leukocyte interactions in viremia.

Cited by 114 publications

References 33 publications

Nuclear expression of the lower matrix protein of human cytomegalovirus in peripheral blood leukocytes of immunocompromised viraemic patients

Nuclear expression of the lower matrix protein of human cytomegalovirus in peripheral blood leukocytes of immunocompromised viraemic patients

Polymorphonuclear cells are not sites of persistence of human cytomegalovirus in healthy individuals

Novel Functions of Tyrosine Kinase 2 in the Antiviral Defense against Murine Cytomegalovirus

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