Rubella Virus Carrier Cultures Derived From Congenitally Infected Infants

Abstract

Spontaneous rubella carrier cultures derived from tissues of infants with congenital rubella were studied in an attempt to elucidate a possible mechanism for viral persistence observed in these infants. Chronically infected cells were found to have a reduced growth rate and the cultures appeared to have a shortened life span. The rubella carrier state was not dependent on serum inhibitors or rubella antibodies. Virtually every cell in the carrier population was found to be producing virus. The carrier cultures could not be cured by rubella antibodies. The rubella-infected cells were resistant to superinfection with vesicular stomatitis virus and herpes simplex virus but were susceptible to infection with echovirus 11. The replication of vesicular stomatitis virus was apparently blocked at an intracellular site, for the virus readily adsorbed to the chronically infected cells and entered into an eclipse phase; however no infectious virus developed. No evidence of interferon production by these cells could be obtained. It is postulated that clones of rubella-infected cells in vivo, with properties similar to those in carrier cultures developed in vitro from tissues of in utero infected infants, might explain the observed viral persistence noted in congenital rubella.

Altered growth, differentiation, and responsiveness to epidermal growth factor of human embryonic mesenchymal cells of palate by persistent rubella virus infection.

“…Furthermore, HEMP cell growth was also affected (Fig. 3 A), which is compatible with the previous reports (21,25), and stimulation ofgrowth by EGF was impaired in HEMP-RV cells (Table I) acetylcholine were significantly altered (26). Recently, the same virus has been shown to perturb endocrine function of pituitary gland cells in experimental animals (27,28 (29).…”

“…Although there are several reports that describe establishment of diploid cells in RV carrier states, these cells were isolated from cogenitally infected human embryos and infants and showed comparably slow growth and limited life span (22)(23)(24)(25), and were therefore unsuitable for extensive study of the pathogenesis of the rubella syndrome. Since epidemiological and serovirological studies suggest that the congenital rubella syndrome is due to chronic or persistent infection ofhuman embryos with RV, establishment of a suitable RV-infected embryonic cell line of human origin with functional markers of differentiation and growth is essential to elucidate the precise mechanism of viral pathogenesis.…”

Studies on the Persistent Infection with Measles Virus in HeLa Cells

“…In this sys tem, the maintenance of the carrier state seemed to depend on the ability of the cells releasing infectious virus to replicate and form colonies under the presence of anti measles serum. Similar systems were re ported in the carrier state of measles virus [9,11,12], mumps virus [14,15], rabies virus [2], rubella virus [5,10], arbovirus [7], parainfluenza virus HA2 [3,4,8], parainflu enza virus HVJ [6], and parainfluenza virus SV5 [1]. A unique property of HeLa/MV culture was that only 6 to 18% of cells were releasing infectious virus at any given time though virtually all cells appeared to have been infected.…”

Characteristics of a Persistent Rubella Infection in a Human Cell Line

“…Development of techniques for the isolation and identification of rubella virus led to the discovery that infection of the foetus by rubella virus during the first trimester of pregnancy may often result in a chronic or persistent infection and persistently infected cell lines have been established using tissue from infected human foetuses and newborn infants (Goffe, 1965;Rawls & Melnick, 1966). In addition, persistent infections have been established in continuous laboratory cell lines: RK-13 (Svedmyr, 1965), LLC-MK2 (Maassab & Veronelli, 1966) and BHK-21/WI-2 (Sato et al, 1977).…”