**2. Influenza Virion**

Influenza virions are particles with a diameter of 80–100 nm, coated with a lipid membrane with an integrated surface of three types of glycoproteins: hemagglutinin (HA), neuraminidase (NA), and the viral ion channel (M2) [13]. On one side, this membrane is in contact with the cytoplasmic domains of HA and NA, and on another, with the core of the virion. The ribonucleoprotein (RNP) is represented by eight segments of the genome: single-stranded negative-polarity RNA in a complex with the nucleoprotein protein and three subunits of the polymerase complex [14,15]. After the virus enters the cell, the ribonucleoprotein gets to the nucleus, where transcription, translation, and replication of segments of the viral genome occur (Figure 1).

**Figure 1.** The life cycle of influenza virus.

The binding of the influenza virus with cell sial-containing receptors creates surface glycoproteins, i.e., hemagglutinin (HA), neuraminidase (NA), and viral ion channel (M2). Influenza virus penetration into the cell and fusion with endosome: HA contributes to the release of free nucleocapsid in the cytoplasm (the so-called fusion sites). M2 is involved process of "disassembly" of the virus in endosomes and the Golgi apparatus. Transcription and replication of the viral genome creates transcription and replication of virus-specific RNAs carried out by a viral polymerase complex. Ribonucleoprotein (RNP) enters the cytoplasm and then into the nucleus. The release of the RNA virus in the cytoplasm allows for NA to end the replication and helps to separate matured virion from epithelial cells. Further, the matrix protein (M1) comes into contact with the cytoplasmic domains of HA, NA, and the core of virion. M1 plays an important role in the assembly and disassembly processes of new virus particle.

Transcription and replication of virus-specific RNAs are carried out by a viral polymerase complex. Unlike the polymerases of eukaryotic cells, viral polymerase has no error correction mechanism. Therefore, the frequency of mutations of the viral genome is, according to various estimates, from 10−<sup>4</sup> to 10−<sup>6</sup> nucleotides per replication cycle [16,17]. This is several orders of magnitude higher than the rate of mutation in bacteria and eukaryotes [18]. Due to a short life cycle, the evolution of the influenza virus is fast. As a result, the rapid appearance of mutations allows the virus to escape the host's immune response [19,20]. Thus, it can cause annual epidemics, despite the formation of an immune layer in the population due to vaccination and natural incidence. In addition, as result of the use of antiviral drugs, drug-resistant strains of the virus have developed, leading in a decrease in the effectiveness of antiviral chemotherapy [21].

Influenza virus, like all complex viruses, has a supercapsid, i.e., an additional envelope or peplos, the structural elements of which are peplomer, including HA and NA [22]. The capsid encloses the genome of the virus. Three types of influenza virus (genera) have been described: A, B, and C [23]. Type B and C viruses cause disease only in humans. Hemagglutinin and neuraminidase carry antigenic determinants of the influenza virus and determine its subtype (H5N1, H3N2, H1N1, etc.). Influenza hemagglutinin is a highly variable surface glycoprotein, with 17 known antigenic subtypes [24]. The main function of hemagglutinin is receptory, i.e., it mediates the attachment of virions to target cells by binding to sial-containing receptors [25]. Hemagglutinin is the main specific antigen of the virus, causing the formation of antibodies that neutralize the infectivity of the virus. The presence of antibodies against HA is the main criterion for assessing the post-infectious or post-vaccination humoral immune response to the influenza virus [21].

However, the value of HA is not limited to physical contacts between the virus and the cell. It continues to act in the subsequent stages of infection, contributing to the release of free nucleocapsid into the cytoplasm. This occurs in the acidic environment of endosomes (phagolysosomes), due to the special structures of HA (its so-called fusion sites) that promote the unification of viral and cellular membranes.

The NA of influenza destroys sialic acid-based cell receptors on infected cell surfaces and on virions after generation, and thereby prevents virion self-aggregation, facilitating the passage of the virus through mucin during a natural infection. In influenza A viruses, there are nine subtypes of NA, but there is only one NA in B and C viruses. The NA separates the virions from sialylated mucins that cover the mucosa, promoting virus attachment to the surface of epithelial cells. At the end of the replication cycle, it helps to separate mature virions from epithelial cells. In both cases, NA acts as a spreading factor, expanding the area of infection. That is why antibodies to NA show a protective effect, but weaker than antibodies against HA [26].

The nucleoprotein of influenza virus (NP) is the main antigen recognized by cytotoxic T lymphocytes. Amino acid sequences 260–283 of the nucleoprotein of influenza A virus induce the T cell response. The NP of influenza virus is a major factor in the cycle of viral infection when switching the synthesis of influenza virus RNA from transcription mode to replication mode [25].

Protein M1 is the matrix protein of the influenza virus; it covers the lipid membrane. It is in contact with the cytoplasmic tails of HA and NA, and it is bound to the ribonucleoprotein complex of the virus [27]. This protein plays an important role in the assembly and disassembly processes of new virus particles [28]. Membrane protein M2 is an influenza virus surface protein that participates in the creation of an ion channel that regulates pH while disassembling the virus in endosomes and the Golgi apparatus. An acidic pH is a prerequisite for disassembly the virus and stabilizing it during intracellular transport. Viruses with a defect in the activity of this ion channel have poor reproduction efficiency [29].
