ROTTERDAM, NETHERLANDS—Virtually all children in the Netherlands older than 5 years have been exposed to a previously undescribed virus isolated from 28 children with symptoms ranging from upper respiratory tract infection (RTI) to severe bronchiolitis and pneumonia. “The disease is clinically indistinguishable from that caused by RSV [human respiratory syncytial virus],” commented Albert D. M. E. Osterhaus, DVM, PhD.

Discovered by Dr. Osterhaus and his colleagues at Erasmus Medical Center in Rotterdam, the virus, dubbed human metapneumovirus (hMPV), appears closely related to avian pneumovirus.[1]

“In the children’s hospital, we see many patients with respiratory disease, especially in the winter months. RSV is the single most important pathogen. But in about 10% to 20% we never find the causative agent,” said Dr. Osterhaus, a Professor at Erasmus.

During the winter of 2000, nasopharyngeal aspirate samples were collected from 68 children presenting with RTIs at Erasmus who tested negative for RSV, influenza A and B, parainfluenza virus types 1 to 3, human rhinovirus, and corona virus. Using reverse transcription polymerase chain reaction, hMPV was detected in seven of the 68. Therefore, hMPV may account for approximately 10% of all unexplained RTIs.

Serologic testing of samples from the general population in the Netherlands grouped by age showed that of 20 infants ages 6 months to 1 year, 25% were seropositive. Children ages 1 to 2 years and 2 to 5 years showed 55% and 70% seropositivity, respectively. “By the age of 5 years, all have seroconverted,” said Dr. Osterhaus, based on the sampling. The researchers also tested 72 sera obtained from adults in 1958; all had antibodies to the virus, indicating that its prevalence did not develop recently. “The virus has been around for at least 50 years,” Dr. Osterhaus remarked.

Symptoms of hMPV infection were frequently severe in young children, requiring hospitalization and mechanical ventilation, but, Dr. Osterhaus noted, “these patients are somewhat pre-selected—in our clinic, we probably see the severest cases.” Unlike another member of its genus, a metapneumovirus that infects turkeys, hMPV could not replicate in birds. However, Dr. Osterhaus told PULMONARY REVIEWS, “Monkeys were readily infected and developed mild respiratory symptoms.” Susceptibility of primates but not birds to the virus, together with the epidemiological data, suggests humans as the primary hosts.

Why has this widespread virus remained uncharacterized until now? The authors partly attribute the virus’ anonymity to its poor replication in standard culture. “We use different cells than other laboratories to culture the virus (tertiary monkey kidney cells), and we keep the cells longer—the virus appears to take more than 10 days after inoculation to cause cytopathic changes,” Dr. Osterhaus explained.

Further , lack of immunological cross-reactivity and poor sequence homology with known viruses allowed hMPV in patient samples to escape detection with diagnostics for other viruses.

—Mimi Zucker, PhD

Reference
1. Van Den Hoogen BG, De Jong JC, Groen J, et al. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med. 2001;7:719-724.

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