engleski

Structure and origin of mumps virus defective interfering particles

Defective interfering viral particles (DIPs) arise naturally during viral replication. They are packaged into viral particles, but cannot replicate without the co-infection with helper/non-defective virus. However, once the co-replication takes place, the DIPs replicate preferentially over non-defective virus. DIPs were shown to posses multiple biological activities: they are essential for induction of type I interferons, they attenuate pathogenic effect caused by a complete viral particle and enhance the maturation of dendritic cells. The knowledge of the mechanism by which DIPs genomes are generated is scarce in spite of their significance during infection. To identify mechanisms involved in the displacement of viral RdRp during genome replication, we amplified and sequenced copy-back DIP genomes of three mumps virus strains JL5, UrabeAM9 and L-Zagreb. We identified three types of DIPs for JL5 and five types of DIPs for UrabeAM9 and L-Zagreb ranging from approx. 750 nt up to 1.6 kb. The length of the complementary ends was unique for every DIPs identified by sequence analysis and the range was 72 to 347 nucleotides. Our findings indicate a strain specific nature of DIP. Further experiments show that the generation of DIPs is non-random by nature. The mechanism underlying generation of DIPs is unknown. Some studies report on the importance of RNAi mechanisms. Hence we investigated the generation of MuV DIPs in the Tet-inducible dicer knock-down cell system. Our finding shows that a host dicer protein is not required for the replication of preexisting DIPs, but is indispensable for de novo generation of DIPs.

Mumps virus; defective interfering particles

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