P~ 94(Received for publication, July 13, 1962.) Viral carrier states in cell cultures have been described by several investigators using a variety of virus-cell systems (reviewed in reference 1). Because of techniques applicable to cell cultures, such carrier states would seem to offer particularly good opportunities to gain understanding of interactions of virus and cell that may be important to those naturally occurring infections in which viruses invade and remain in hosts for relatively long periods without causing apparent harm. From the studies already reported, however, it is evident that there is considerable variation in the virus-cell relationships found in carrier systems in vitro. This is to be expected since, at least superficially, the examples of persistent, inapparent viral infections found in man and animals present a diversity of characteristics. Those carrier cultures so far described have, however, usually had several things in common in that they often have utilized cells relatively resistant to the virus; many have required antibody in the medium or have appeared to depend upon some form of interference for protection of the cells; many show evidence for infection of only a small proportion of the cells in the culture. In this and the following paper we shall describe a virus carrier system that is unusual in its combination of features that include (a) lack of any requirement for antibody, (b) indication that there is not a selection of resistant cells, (c) alteration in the cytopathogenicity of the persisting virus, (d) infection of almost all of the cells of the culture, and (e) indication that infected cells are capable of repeated division. Materials and MethodsViruses.--The Dunai strain of mumps virus was isolated from a patient with parotitis (2) by inoculation of throat washings into the amniotie sac of the chick embryo. After the initial amniofic passage, it was cultivated in human conjunctiva cells.

A viral agent has been isolated from naturally infected wild cottontail rabbits (Sylvilagus floridanus). The virus appears to have the general physical, chemical, and biological properties of the herpesvirus group. It differs significantly in host range and antigenic structure from the previously recognized herpesviruses and is proposed as a new member of this group of viruses. The name of Herpesvirus sylvilagus is suggested for the agent.

Herpesvirus sylvilagus, a recently recognized virus indigenous to cottontail rabbits, was examined for its ability to produce experimental disease in its natural host. Infection led to the establishment of a persisting low‐grade viremia in which virus was found in the cellular portion of the blood for the entire observation period. Pathologic changes seen in infected animals were related exclusively to stimulation of the lymphoid organs which varied in intensity from mild to apparently malignant. The response in all cotton tails was a generalized lymphoid hyperplasia with a corresponding lymphocytosis and the appearance of large numbers of abnormal mononuclear cells in the peripheral blood. In addition, 27% of immature cottontails (juveniles) and 10% of adult animals showed a loss of normal lymph‐node structure and massive mononuclear cell infiltration of other organs which was unrelated to destruction of parenchymal cells by the virus and which resembled, in some respects, the histologic picture seen in malignant lymphoma.

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Cultural changes that follow infection of rabbit kidney cells with fibroma virus were studied. Characteristic alterations of cell morphology and development of multilayered piles and cords of cells were found to occur in infected cultures in which cell division was blocked by gamma radiation or by cell crowding and serum deprivation, thus indicating no dependence upon cell division. Fibroma virus infection did not remove blocks to cell division, but it did exert distinct effects upon nuclear deoxyribonucleic acid synthesis in cells blocked by radiation or cell crowding. Use of tritium-labeled thymidine and autoradiography demonstrated that after infection initial inhibition of nuclear incorporation was followed by sharply increased nuclear labeling at a time that coincided with beginning alterations of cell morphology and development of cell piling. MATERPALS AND METHODS Cells. Domestic rabbit kidney (DRK) cells, a strain of epithelial cells of New Zealand white rabbit origin (8), were used between the 20th and 35th subcultures.