Detection of Minute virus of mice strains in different cell lines: Implications for adventitious agent testing

Abstract

AbstractMinute virus of mice (MMV) has contaminated biotechnological processes in the past and specific MMV testing is therefore recommended, if the production cell line is known to be permissive for this virus. Testing is widely done using cell‐culture‐based adventitious virus assays, yet MMV strains may differ in their in vitro cell tropism. Here, we investigated the growth characteristics of different MMV strains on A9 and 324K cells and identified significant differences in susceptibility of these widely used indicator cell lines to infection by different strains of MMV, which has implications for MMV detectability during routine testing of biotechnology process harvests. An MMV‐specific polymerase chain reaction was evaluated as a more encompassing method and was shown as suitable replacement for cell culture‐based detection of the different MMV strains, with the additional benefit that detection is more rapid and can be extended to other rodent parvoviruses that might contaminate biotechnological processes. Although no MMV contamination event of human‐derived cell lines has happened in the past, biotechnological processes that are based on these also need to consider MMV‐specific testing, as, for example, HEK293, a human‐derived cell line commonly used in biopharmaceutical manufacturing, was shown as susceptible to productive MMV infection in the current work.