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300 || AWSAR Awarded Popular Science Stories - 2019
its genome and transcription, vRNAs enter into the nucleus. After transcription, mRNAs exit the nucleus, under goes translation and produce proteins. However, the mechanism of assembly and packaging is a bit of unsolved mystery.
Packaging and assembly of virus
Like any other viruses, replication of IAV is also totally dependent on host cell machinery and acts like a non-living outside host. One of the most important parts of IAV life cycle is protein synthesis and this is completely mediated by host cell translation machinery. The function is divided between two kinds of ribosomes of the host. Most of the proteins, like PB1, PB2, M1, NS, PA, and NP are synthesized by cytosolic ribosome. However, other proteins like HA, NA, M2 are synthesized by endoplasmic reticulum associated ribosome. After synthesis, proteins get busy with their corresponding function with a mission to infect a new cell.
For that, some proteins remain
in the cytosol, for example,
NS1. It suppresses the host
cell’s anti-viral response. While
some proteins contain specific
signal sequence that targets
them to specific location with
particular function. PB1, PB2,
and PA enter the brain of the cell
using importin protein to guide
nuclear proteins to synthesize
more viral mRNA and vRNA to
accomplish the mission. HA,
NA contains a stretch of amino
acids which are hydrophobic.
These proteins do not like the
aqueous environment of cytosol thus they need to hide somewhere else. Following the synthesis of hydrophobic signal sequences, it is recognized by signal recognition particle (SRP), a guiding protein, to assist them to reach a safe shelter, which is endoplasmic
reticulum. Inside the ER, they not only get the shelter, but gain some other modifications which also help them to get dressed properly. Disulfide bond formation, oligosaccharide chain addition favoured them to get the correct folding. Here HA, NA undergoes trimerization and tetramerization, respectively, which will give them the structure with best functions.
Once they are dressed and prepared properly, they become ready to infect a new host. Now they need to assemble. Since they need to deceive the landlord, they disguise themselves in the same feather. They pinch- off a part of the host cell membrane and wrap themselves in it. That’s why IAV envelope is rich in cholesterol. C-terminal cysteine modification of HA inside golgi targets it to the apical surface of host. Trans-membrane domain of NA targets it at the budding site. Here M1 acts as a bridge between the envelop and other vRNPs. And, finally, Rab11 protein helps the
viral RNPs to exit the nucleus and to reach its destination, that is, the assembly site. M2 protein has an amphiphillic helix, where amino acid residues get incorporated into lipid bilayer leaflet and introduce negative bending. This negative membrane curvature is proposed to facilitate bed neck formation, reduce the distance between two opposing membranes of the viral envelop and achieve the ultimate goal, that is, to get released as a functional, infective virion or virus.
Visualization of movement of HA
It is always fascinating to image any intracellular event at a molecular level. However, sometimes there are many obstructions. This is applicable here as well. Some common
   Influenza virus is the prime mover of Influenza, an acute respiratory disease, commonly called ‘flu’. It is the cause of global mortality and morbidity with seasonal epidemics and sporadic pandemics. The pandemic strain H1N1 resulted in so severe a flu that it infected around 22 million people around the world.
  







































































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