Saira K, Lin X, Depasse JV, Halpin R, Twaddle A, Stockwell T, Angus B, Cozzi-Lepri A, Delfino M, Dugan V, Dwyer DE, Freiberg M, Horban A, Losso M, Lynfield R, Wentworth DN, Holmes EC, Davey R, Wentworth DE, Ghedin E, INSIGHT FLU002 FLU003 Study Groups
Sequence Analysis of In Vivo Defective-interfering (DI)-like RNA of Influenza A H1N1 Pandemic Virus.
Journal of Virology. 2013 May 15;
Influenza virus defective interfering (DI) particles are naturally occurring non-infectious virions typically generated during in vitro serial passages in cell culture of the virus at high multiplicity of infection. DI particles are recognized for the role they play in inhibiting viral replication, and for the impact they have on the production of infectious virions. To date, influenza virus DI particles have been reported primarily as a phenomenon of cell culture and in experimentally infected embryonated chicken eggs. They have also been isolated from a respiratory infection of chickens. Using a sequencing approach we characterize several subgenomic viral RNAs from human naso-pharyngeal specimens infected with the influenza A (H1N1)pdm09 virus. Distribution of these in vivo-derived DI-like RNAs was similar to that of in vitro DIs, with the majority of the defective RNAs generated from the PB2 (segment 1) of the polymerase complex, followed by PB1 and PA. The in vivo-derived DI-like segments are also of similar length as known in vitro DIs and share internal deletions of the same segments. The presence of identical DI-like RNAs in patients linked by direct contact is compatible with transmission between them. The functional role of DI-like RNAs in natural infections remains to be established.