Journal of Experimental Medicine, Vol 147, 1637-1652, Copyright © 1978 by Rockefeller University Press
Isolation of a heterogeneous population of temperature-sensitive mutants of measles virus from persistently infected human lymphoblastoid cell lines
G Ju, S Udem, B Rager-Zisman and BR Bloom
Two human lymphoblastoid B-cell lines, WI-L2 and 8866, were infected with
the Edmonston strain of measles virus at a multiplicity of infection of
10(-6), and stable persistent infections were established. By
immunofluorescence and electron microscopy, the vast majority of cells from
both cell lines were expressing viral antigens and releasing virion-like
particles. However, very little infectious virus could be detected at 37
degrees C, either by an infectious centers assay or by titration of
supernates from persistently infected cultures. When cultures were shifted
to 31 degrees C, the cells released a population of virus that was
temperature-sensitive. Clonal analysis of supernatant virus at 31 degrees C
revealed a highly heterogeneous population of temperature-sensitive
mutants, differing in plating efficiency ratios, thermolability, and
antigen production at the nonpermissive temperature. Factors such as
interferon, defective interfering particles, and extracellular virus do not
appear to be important in maintaining the persistent carrier state. These
studies have important implications for persistent infections of lymphoid
cells in vivo, and the slow neurological diseases associated with measles,
subacute sclerosing panencephalitis, and multiple sclerosis.
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