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Abstract:
Defective interfering particles (DIPs) of the influenza virus are non-infectious particles,
which can only replicate in cells that are co-infected with a wild-type virus. Because of
an advantage in replication, DIPs strongly interfere with virus production in these coinfections
and dramatically reduce virus yields during cell culture-based vaccine production.
To examine the interference of DIPs systematically, we developed a mathematical
model, which describes the replication of DIPs and wt particles in a single co-infected
cell. Intriguingly, our results show a significant decrease in total viral protein production
leading to a shortage of both the nucleoprotein (NP) and the viral polymerase complex.
The low number of these two proteins can limit the replication of viral genome copies,
thereby impairing the release of progeny virions. We identified three major factors affecting
DIP replication and virus release: (i) the length of the defective segment, (ii) the
time of co-infection and (iii) the number of infecting particles. Furthermore, we propose
that there is only a small time window after wt-infection, in which the co-infection with
DIPs alters viral replication. Hence, our newly developed model provides an ideal basis
for studying the intracellular dynamics of viral genome segments and viral proteins
upon co-infection with defective interfering particles.
