Detection of cytomegalovirus in bronchoalveolar lavage fluid from immunocompromised patients with pneumonitis by viral culture and DNA quantification

Abstract

Purpose To compare the detection of human cytomegalovirus (HCMV) in bronchoalveolar lavage (BAL) fluid by viral culture and quantitative polymerase chain reaction (qPCR), and to establish a viral load threshold that can identify cases of HCMV replication indicative of pneumonitis. There is currently no universal viral load cut-off to differentiate between patients with and without pneumonitis, and the interpretation of qPCR results is challenging. Methods 176 consecutive BAL samples from immunosuppressed hosts with signs and/or symptoms of respiratory infection were prospectively studied by viral culture and qPCR. Results Concordant results were obtained in 81.25% of the BAL samples. The rest (18.75%) were discordant, as only 34% of the qPCR-positive BAL samples were positive by culture. The median HCMV load was significantly higher in culture-positive than in culture-negative BAL samples (25,188 vs 890 copies/mL). HCMV was isolated in 100% of the BAL cultures with a viral load of > 4,500 copies/mL. Conclusion Availability of reference values for the HCMV load in BAL fluid facilitates the interpretation of qPCR results and clinical decision-making. We found that a negative PCR test was a quick and reliable way of ruling out HCMV pneumonitis, but a positive result did not always indicate clinically significant replication in the lung. However, an HCMV load in BAL fluid of > 4,500 copies/mL was always associated with the disease, whereas < 1,000 copies/mL rarely so. These data may be useful for centres without access to gold-standard techniques.

MORC3 represses the HCMV major immediate early promoter in myeloid cells in the absence of PML nuclear bodies

“…Human cytomegalovirus (HCMV) is a ubiquitous beta‐herpesvirus that infects up to 99% of individuals in certain populations, depending on demographics. The virus is generally asymptomatic in immune competent individuals but causes a major disease burden in the immune compromised/suppressed, such as transplant patients, or in immune naïve neonates 1–3 . This is partly explained by the fact, after primary infection, virus establishes a lifelong latent infection in the host during which time the production of infectious virions is undetectable.…”