Discovery of cytomegalovirus

The history of the discovery of CMV is closely linked to the study of fetuses and newborns who died and had pathologic findings of multiorgan involvement suggestive of congenital infection (see review in Riley, 1997). Features consistent with CMV cytopathology were described more than 50 years prior to the isolation of CMV, including intranuclear inclusions, though the viral etiology of these changes was not at first recognized. Cytopathologic changes similar to those seen in autopsies of fetuses and newborns were subsequently described in salivary glands and other organs of infants and children. The term "cytomegalia" was first used in 1921, and the presence of this cytopathology in stillbirths was considered evidence of a prenatal insult. The possibility that the responsible agent might be more common than the congenital disease was suggested by a report of cells with intranuclear and intracytoplasmic inclusions in 14 percent of salivary glands from 183 infant postmortem examinations (Farber and Wolbach, 1932). In the early 1950s, the term "generalized cytomegalic inclusion disease" was used to describe the infants with multiorgan involvement (Wyatt et al., 1950). Detection of inclusion-containing cells in urine was described as an early diagnostic technique, and developmental delay and cerebral palsy were reported in a surviving infant prior to the isolation of CMV (Fetterman, 1952; Margileth, 1955).

Weller, one of the discoverers of human CMV, reviewed the circumstances and chronology of the initial tissue culture isolation of CMV which occurred in three laboratories at roughly the same time in the mid-1950s (Weller, 1970). The first isolation of CMV from tissues of a living human was made serendipitously in 1955, when Weller's laboratory was attempting to isolate Toxoplasma from a liver biopsy taken from an infant with hepatosplenomegaly, cerebral calcification, and chorioretinitis; the focal cytopathic effect that developed in tissue culture was typical of cytomega-loviruses, and Weller and colleagues concluded that they had recovered the agent of cytomegalic inclusion disease. Shortly afterwards, it was possible to prepare antigens for serologic testing. Study of sera from adults showed that the majority were antibody-positive, showing that CMV infections are common (Rowe et al., 1956).

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