vRNA-vRNA interactions in influenza A virus HA vRNA packaging

The genome of the influenza A virus is composed of eight single-stranded negative-sense RNA segments (vRNAs). The eight different vRNAs are selectively packaged into progeny virions. This process likely involves specific interactions among vRNAs via segment-specific packaging signals located in the...

Full description

Saved in:
Bibliographic Details
Published inbioRxiv
Main Authors Miyamoto, Sho, Muramoto, Yukiko, Shindo, Keiko, Fujita, Yoko, Morikawa, Takeshi, Tamura, Ryoma, Gilmore, Jamie Lynn, Nakano, Masahiro, Noda, Takeshi
Format Paper
LanguageEnglish
Japanese
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 16.01.2020
Subjects
Genomes
Hemagglutinins
Influenza
Influenza A
Mutants
Mutation
Packaging
Pandemics
Ribonucleic acid
RNA
Virions
Viruses
Online AccessGet full text

Cover

More Information
Summary:The genome of the influenza A virus is composed of eight single-stranded negative-sense RNA segments (vRNAs). The eight different vRNAs are selectively packaged into progeny virions. This process likely involves specific interactions among vRNAs via segment-specific packaging signals located in the 3' and 5' terminal coding regions of vRNAs. To identify vRNA(s) that interact with hemagglutinin (HA) vRNA during genome packaging, we generated a mutant virus, HA 5m2, which possessed five silent mutations in the 5' packaging signal region of HA vRNA. The HA 5m2 virus had a specific defect in HA vRNA incorporation, which reduced the viral replication efficiency. After serial passaging in cells, the virus acquired additional mutations in the 5' terminal packaging signal regions of both HA and PB2 vRNAs. These mutations contributed to recovery of viral growth and packaging efficiency of HA vRNA. A direct RNA-RNA interaction between the 5' ends of HA and PB2 vRNAs was confirmed in vitro. Our results indicate that direct interactions of HA vRNA with PB2 vRNA via their packaging signal regions are important for selective genome packaging and enhance our knowledge on the emergence of pandemic influenza viruses through genetic reassortment.
DOI:10.1101/2020.01.15.907295