STUDIES ON PERSISTENT INFECTIONS OF TISSUE CULTURES

Abstract

Efforts were made to obtain information on some of the quantitative aspects of host cell-virus interactions in MCN cultures persistently infected with Newcastle disease, mumps, and 6-6 viruses, and to elicit the mechanism which permits simultaneous maintenance of virus and cells for indefinite periods of time. It was shown by 4 different techniques that only between 10 and less than 1% of the cells yield infectious virus, depending upon the agent employed and possibly variations in the conditions of the cultures. No evidence was found to indicate production of non-infectious virus materials. Only the cells carrying infectious virus are capable upon transfer to uninfected cultures of transmitting the infection. Cells from persistently infected cultures, which are free of infectious virus at the time of transfer, failed to liberate virus at a later time during incubation periods of up to 4 weeks. The virus-producing cells contain at any given moment not more than 1 infectious unit of virus, suggesting a linear mode of production; i.e., as soon as a virus particle is completed, it is released. Upon inoculation of MCN test tube cultures with chick embryo-adapted NDV, persistent infection and interference with vesicular stomatitis virus (VSV) is established with considerable delay. In contrast, following transfer of MCN-adapted NDV, in form of MCNNDV cells or first allantoic passage seeds derived therefrom, the number of virus-producing cells increases logarithmically, doubling every 6 to 8 hours until a total of about 104 is reached. Thereafter their numbers rise in proportion to the increase in total cell population; i.e., doubling approximately every 48 hours. At the time when 104 virus-producing cells are present in the culture interference with VSV is solidly established. In order to obtain this result about 106 cells must have adsorbed virus particles, or, in other words, at least 106 virus units in toto must have been produced instead of the 104 measured by infectivity assay. The implications of these and previously reported data have been discussed in detail and a scheme of the course of events in persistently infected cultures has been presented.