Transmission:

 Virus travels via air in droplets when an infected person cough, sneeze, or talk
 Virus invades the epithelial cell of the upper respiratory tract.

Entry:

 Influenza virus enters the cell through a receptor-mediated endocytosis, the sialic acid
substances on the plasma membrane function as an entry receptor.
 Following endocytosis, the virus molecules are situated inside the endosome, and since
the latter has acidic pH, it induces the fusion between the two membranes.
 In the endosome, through M2 ion channel, the protons are imported inside the viral
envelope
 the nucleocapsids make up of vRNA, NP, and RdRp inside the envelope are discharged
to the cytoplasm and then enter the nucleus via nuclear pore

Transcription

 The RdRp of the influenza needs a primer for the transcription initiation and via cap-
snatching mechanism; the endonuclease activity of PA splits a capped RNA fragment
from the 5’ end of cellular mRNAs, which is utilized as a primer for viral mRNA.
 Shuttering occurs as it copied repeatedly the short runs of U residues at the 5’ end of
vRNA to make the tail and through template-dependent manner viral mRNA at the 3’ end
is joined. Viral transcription is stopped after polyadenylation.
 Viral mRNAs resultant is transported to cytoplasm and used as mRNA for the viral
protein synthesis.

Replication:

 Viral genome replication and viral mRNA synthesis take place upon the entry of vRNPs
into the nucleus.
 Nucleocapsid protein modulates the process of mRNA and cRNA sythesized using the
negative-sense RNA as template.
 Synthesizing vRNA is done by using a cRNA template and the budding vRNA is
enclosed by the NP which forms the vRNP

Translation Nuclear export

 Transported to cytoplasm are the viral mRNAs and afterward serve as mRNA for the
viral protein synthesis.
 Through secretary pathway HA and NA envelope proteins are translated in relation to
Endoplasmic Reticulum and Golgi apparatus.
Nuclear export

 Through nuclear pore, budding vRNPs are penetrated to the cytoplasm, where viral
genome replication takes place.

 M1 protein and NEP assists the nuclear export of vRNPs by binding M1 to vRNP, and
via the interaction of NEP to M1 it indirectly links to vRNP.

 Budding vRNPs in the nucleus are exported out of the cytoplasm via Crm-1- dependent
mechanism or protein export pathway.

Assembly and Release

 Cytoplasmic transport is a process where vRNAs are involved with the microtubule and
move toward the cell surface in a microtubule dependent way.
 Nucleocapsid is moved in the other path to the entry by the microtubule-driven transport.
 After the arrival near the plasma membrane, a set of vRNPs clustered together and then
engages with HA and NA that is already integrated in the plasma membrane
 During the assembly and budding process, M1 plays an essential part since an
engagement between M1 and envelope glycoproteins induces a bud formation.
 M1 proteins employ the vRNPs, and the neuraminidase activity of NA splits the HA in
the budding virions connected to the plasma membrane via sialic acid.