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J Gen Virol. PB2 and PA Genes Control the Expression of the Temperature Sensitive Phenotype of Cold-Adapted B/USSR/60/69 Influenza Master Donor Virus.

Giuseppe

Emeritus
J Gen Virol.. [Epub ahead of print]

PB2 and PA Genes Control the Expression of the Temperature Sensitive Phenotype of Cold-Adapted B/USSR/60/69 Influenza Master Donor Virus.

Kiseleva I, Voeten T, Teley L, Larionova N, Drieszen-van der Cruijsen S, Basten S, Heldens J, van den Bosch H, Rudenko L.

Insitute of Experimental Medicine, Saint Petersburg, Russia;

The cold-adapted (ca) and temperature sensitive (ts) influenza Master Donor Virus (MDV) B/USSR/60/69 was derived from its wild type parental virus after successive passages in eggs at 32 degrees C and 25 degrees C. This strain is currently in use for preparing reassortant influenza B vaccine viruses which are used in the Russian trivalent live attenuated influenza vaccine. Vaccine viruses are obtained by classical reassortment of MDV and a currently circulating wild type virus. The phenotypic properties cold adaptation and temperature sensitivity are inherited from the six genes encoding the internal proteins of the MDV. However, the role of the individual gene segments in temperature sensitivity and thus attenuation is not known. In this study, 35 reassortant viruses of B/USSR/60/69 MDV with current wild type non-temperature sensitive influenza B viruses were generated in eggs or MDCK cells and studied in order to identify the genes responsible for their ts phenotype. For each virus the exact genome composition was determined as well as its ts phenotype. Results demonstrated that the polymerase PB2 and PA gene segments of B/USSR/60/69 MDV independently controlled expression of the ts phenotype of B/USSR/60/69 MDV based reassortant viruses. The other genes coding for internal proteins played no role in this respect. This suggests that mutations in the polymerase genes PB2 and PA play an essential role in attenuation of B/USSR/60/69 MDV based reassortant influenza B vaccine viruses.

PMID: 20007357 [PubMed - as supplied by publisher]

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