Stage 1: Adsorption, endocytosis, and virus «uncoating»
The interaction between the virus and the target cell begins with adsorption. The primary targets for attachment are cellular receptors—specific compounds containing sialic acid. Specifically, these include sialooligosaccharides and lipid complexes located on the plasma membrane. The tropism of the pathogen directly depends on the architecture of the hemagglutinin (HA) «receptor pocket» and the chemical composition of the host cell membrane.
Following successful binding of hemagglutinin to the receptor, the entry mechanism is triggered. The viral particle is captured via endocytosis: an endocytic vacuole forms around the attached virion and is pulled into the cell.
This is followed by the multi-step process of deproteinization, or virus «uncoating». Initially, only partial deproteinization occurs within the cell. The released viral core is transported to the cell nucleus. Final «uncoating» is completed directly at the nuclear envelope, where the M protein is removed. Only then does the freed nucleocapsid enter the nucleus.
Stage 2: Genome transcription and the «cap-snatching» phenomenon
A key feature of influenza virus replication is the localization of synthesis processes. Unlike most RNA viruses, influenza virus transcription takes place strictly in the cell nucleus.
This process involves a polymerase complex consisting of the PA, PB1, and PB2 proteins, as well as the NP nucleoprotein. To synthesize viral messenger RNA (mRNA), the pathogen utilizes a unique transcription initiation mechanism known as "cap-snatching" (from English cap-snatching).
The mechanism proceeds as follows:
- The virus induces enhanced synthesis of cellular mRNAs.
- The viral PB2 protein recognizes cellular mRNA and «snips off» its protective cap structure along with a 10–13 nucleotide fragment.
- This short fragment is used as a primer to initiate the synthesis of its own viral mRNA.
Once transcription is successfully completed, the finished viral mRNA is transported to the cell cytoplasm, where it binds to cellular ribosomes for the translation of viral proteins.
Stage 3: Replication, nucleocapsid assembly, and virion formation
While viral protein synthesis is underway in the cytoplasm, work on the genome continues in the cell nucleus. There, transcription of the entire RNA segment takes place, along with full genome replication. Replication involves the synthesis of plus-strand RNA, which then serves as a template to create progeny minus-strand RNAs. The assembly of the new nucleocapsid also takes place in the nucleus.
The formed nucleocapsids head toward the cell membranes, where the formation of the mature virion takes place. By the time assembly begins, the infected cell has already incorporated new viral surface glycoproteins into its membrane—hemagglutinin and neuraminidase.
The final stage of reproduction is the release of newly formed viral particles. This process is carried out via budding. The virus captures a patch of the cell membrane, forms an outer envelope, and pinches off from the cell surface.
Briefly: answers to topical questions
Through what mechanisms does the viral envelope fuse with the endosome membrane following endocytosis?
- Endosome acidification (acidificatio) — following endocytosis, an acidic environment is created within the endosome.
- Hemagglutinin conformation change (haemagglutininum) — as a result of acidification, the conformation of hemagglutinin changes.
- Membrane fusion (fusio) — the conformational change of hemagglutinin leads to the fusion of the endosome membrane with the viral envelope.
What role does neuraminidase play in the release of newly formed virions from the cell via budding?
- Disruption of the bond (nexus) — the viral enzyme neuraminidase disrupts the bond between hemagglutinin and sialic acid residues.
- Virion separation (virion) — this ensures the final separation of the virion and prevents its aggregation upon exit from the cell.
- Prevention of aggregation (agregatio) — neuraminidase controls the budding of new virions, preventing them from clumping together and remaining stuck to the surface.
To memorize the «cap-snatching» mechanism, imagine a pickpocket: the virus (PB2 protein) incites a crowd (cellular mRNA synthesis), stealthily «slashes» the cap-hat (snips off 10–13 nucleotides), and places it onto its own RNA to use as a primer for the polymerase complex.
Class and exam questions
Where exactly does transcription of the influenza virus genome take place, and why is this important?
Transcription takes place in the nucleus of the infected cell. This is a unique feature of the influenza virus compared to many other viruses whose life cycle occurs in the cytoplasm.
What is the «cap-snatching» mechanism?
This is a transcription initiation process in which the viral PB2 protein «snips off» the cap structure and a 10–13 nucleotide fragment from cellular mRNA. This fragment is then used as a primer for viral mRNA synthesis.
What structures act as receptors for influenza virus attachment?
The virus attaches to membrane compounds containing sialic acid (sialooligosaccharides and lipids). Binding is ensured by the specific «receptor pocket» of hemagglutinin.
How do new virions exit the infected cell?
Virion assembly occurs on cell membranes into which hemagglutinin and neuraminidase have been previously incorporated. The release of new viral particles itself is carried out via budding.
What else to study on this topic
- The structure of the hemagglutinin «receptor pocket» and its role in determining species specificity.
- The role of the matrix M protein in virion structure and the uncoating process at the nuclear envelope.
- Interaction of polymerase complex subunits (PA, PB1, PB2) during transcription.
- Functions of the surface glycoprotein neuraminidase during the budding and virion release stage.
Study the full topic in the «Microbiology» course
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