M. Colin Jordan

Progressive disease due to ganciclovir-resistant cytomegalovirus in immunocompromised patients.

CYTOMEGALOVIRUS (CMV) infections are a major cause of morbidity and mortality among immunocompromised patients, especially recipients of bone marrow and solid-organ transplants and those with the a...

Association of cervical cytomegaloviruses with venereal disease.

Abstract Parity, race, and use of oral contraceptive agents were not related to recovery of cytomegalovirus (CMV) from the cervix of 196 nonpregnant women, but CMV antibody was more prevalent among black women. Of 120 women examined because of suspected venereal disease, 16 (13.3 per cent) had cervical CMV infection, and seven (5.8 per cent) had cervical herpesvirus infection. Neither virus wag recovered from 76 women having routine examinations. CMV isolation and antibody were significantly more prevalent among those with documented past or active gonococcal infection, but CMV isolation did not correlate with the actual presence of Neisseria gonorrhoeae in the cervical secretions at the time of sampling. The study suggests, but does not prove, an association between cervical CMV infection and venereal disease in this population. (N Engl J Med 288:932–934, 1973)

Modification by Adoptive Humoral Immunity of Murine Cytomegalovirus Infection

The effects of specific antiviral antibody on several aspects of infection with murine cytomegalovirus (CMV) were examined. Administration of immune serum 24 hr before subcutaneous inoculation of 10(5) plaque-forming units of murine CMV prevented detectable viral replication in the tissues of 92% of animals. Protection was associated with the immune globulin fraction and not with normal serum or heterologous antiviral serum. However, the development of latent murine CMV infection was not prevented by prior administration of antibody since immunosuppression with antilymphocyte serum and cortisone 16 weeks later unmasked dormant virus in 17 of 20 animals. In normal animals murine CMV-immune serum administered six days after acute virus infection had been initiated did not influence the outcome; however, in immunosuppressed mice, virus dissemination during acute infection was substantially reduced by specific antibody. These results demonstrate a significant effect of humoral immunity on the course of experimental CMV infection.

Interactions of human cytomegalovirus with leukocytes in vivo: analysis by in situ hybridization

Reactivation of human cytomegalovirus (HCMV) from latency occurs in immunosuppressed individuals and infection is itself immunosuppressive. To better understand the basis for this virally induced impairment of immune function, we have analyzed virus-leukocyte interactions by in situ hybridization. We detected viral DNA in 12 viremic patients in the mononuclear cell population, predominantly in cells identified as monocytes by their morphology and by labelling the cells with a monocyte specific monoclonal antibody prior to in situ hybridization. We detected immediate early RNA in infected cells at frequencies comparable to DNA (10(-3) to 10(-5)). By contrast, no viral transcripts were detected in polymorphonuclear cells and viral DNA was inclusively cytoplasmic in accord with the interpretation that this cell type harbors HCMV in phagosomes. These findings in vivo continue to suggest that infection of monocytes plays an important part in the immunosuppressive effects of HCMV infections.

Quantitation of human cytomegalovirus glycoprotein H gene in cells using competitive PCR and a rapid fluorescence-based detection system

A technique is described for quantitation of the human cytomegalovirus (HCMV) glycoprotein H (gH) gene in cells using a quantitative-competitive polymerase chain reaction (QC-PCR). Two recombinant DNA molecules, differing in size due to a 92-bp deletion within the HCMV gH sequence, were used in co-amplification studies to construct a standard curve from which the copy number of the gH gene present in clinical samples could be interpolated. The use of primers labeled with a fluorescent dye allowed direct detection of the amplified products by measuring the amount of fluorescence emitted by each specific PCR fragment with an automated DNA sequencer coupled to a software program. This system was validated subsequently using bronchoalveolar lavage cells obtained from immunocompromised patients and found to be highly sensitive and reproducible over a range of 5-50,000 HCMV gH copies. This rapid procedure could easily be applied to study the pathogenesis of HCMV infection, identify the patients at high risk of developing HCMV disease, and monitor the effects of antiviral therapy at the molecular level.

Propagation and titration of murine cytomegalovirus in a continuous bone marrow-derived stromal cell line (M2-10B4).

Murine cytomegalovirus (MCMV) can only be propagated effectively in mouse embryo fibroblast (MEF) cells. We demonstrate that MCMV replicates significantly better in M2-10B4 cells, a continuous line of murine bone marrow stromal cells. M2-10B4 cells were also comparable to MEF cells for detection of small amounts of MCMV reactivating from latently infected spleen explants. M2-10B4 cells will be very useful for studies of MCMV pathogenesis.

Congenital cytomegalovirus infection as a result of nonprimary cytomegalovirus disease in a mother with acquired immunodeficiency syndrome

A pregnant woman with acquired immunodeficiency syndrome had nonprimary cytomegalovirus (CMV) viremia and died of complications from Pneumocystis carinii pneumonia and CMV sinusitis and pneumonitis. A boy was delivered by cesarean section at 34 weeks of gestation as the mothers health deteriorated and fetal distress developed. The infant died soon after delivery of interstitial pneumonitis and hyaline membrane disease with invasive CMV disease that affected the kidneys, adrenal glands, and placenta; the CMV strains from the mother and neonate were identical.

Ganciclovir Treatment of Cytomegalovirus Disease in Transplant Recipients and Other Immunocompromised Hosts

Thirty-one immunocompromised patients with severe cytomegalovirus (CMV) disease were treated with intravenous ganciclovir. Twenty-one patients had received transplants--15 bone marrow recipients, five renal allograft recipients, and one liver transplant recipient--while the other ten were immunocompromised due to acquired immunodeficiency syndrome (six), hematologic malignancies (three), and systemic lupus erythematosus (one). They presented with one or more of the following syndromes: CMV pneumonitis (19), CMV of the gastrointestinal tract (six), CMV retinitis (seven), and CMV hepatitis (three). Seventeen (55%) of 31 patients demonstrated clinical improvement during ganciclovir therapy, with the best response seen in the transplant recipients. Viremia ceased in 14 (93.3%) of 15 patients after a mean of 4.7 days of therapy; viruria ceased in eight (53.3%) of 15 patients after a mean of 11 days of therapy. Ganciclovir plasma concentrations at a dosage of 2.5 mg/kg/three times a day were as follows: mean peak, 16.04 mumol/L; mean trough, 2.38 mumol/L. Neutropenia occurred in 11 (35%) of 31 patients and in nine (60%) of 15 bone marrow transplant recipients. We conclude that ganciclovir exerted an antiviral effect against CMV and may play a role in the treatment of CMV disease in patients with depressed immunity, especially bone marrow and organ transplant recipients.