What is the cause of the flu? The genomic product of the flu virus

Abstract: Influenza virus belongs to the Orthomyxoviridae family. It is an enveloped RNA virus with a spherical shape of 80-100 nm in diameter or a filament of thousands of nanometers.

What is the cause of the flu? The genomic product of the flu virus

Cause of influenza

The influenza virus belongs to the Orthomyxoviridae family and is an enveloped RNA virus. Its appearance is spherical with a diameter of 80-100 nm or a filament of thousands of nanometers. The virus consists of the envelope and the nucleocapsid .

The components of the envelope include membrane proteins (M1, M2), bilayer lipid membranes, and glycoprotein protrusions. The glycoprotein neurites contain both hemagglutinin (HA) and neuraminidase (NA), both of which are antigenic and subtype specific. The nucleocapsid is a thin spiral filament, spirally symmetric, 9 to 15 nm in diameter, including nuclear protein (NP), three polymerase proteins (PB-1, PB-2, PA) and viral RNA; the viral genome is single-stranded Negative strand RNA.

Classification and nomenclature of influenza virus According to the different antigenicity of viral nuclear protein (NP) and membrane protein (MP), the influenza virus is divided into three types: A, B, and C; according to the difference of HA and NA antigens, the same type of virus is divided into two types. Several subtypes. Subtype division is based on genetic analysis and agar diffusion double diffusion. The principles of influenza virus nomenclature published by the World Health Organization in 1980 are as follows: type/host/separation site/segregation date/viral strain number (hemagglutinin subtype and neuraminidase subtype). For example, A/equine/Singapore/3/52 (H7/N3), meaning: influenza A virus/host is horse/separated in Singapore/time is March 1952/subtype is H7N3. Up to now, there have been 15 subtypes of hemagglutinin (H1~15), and 9 subtypes (N1~9) of neuraminidase. The main ones related to humans are A1 (H1N1), A. 2 (H2N2), A3 (H3N2) and Type B.


Influenza virus stability The influenza virus is the most stable between pH 6.5 and pH 7.9, and has weak resistance to high temperature. It loses pathogenicity after heating to 56 ° C for several minutes, and is inactivated at 100 ° C for 1 min. The virus is relatively stable, can survive for more than 1 month at 4 °C, and can survive for more than 5 months at -70 °C. The influenza virus is sensitive to dry, ultraviolet radiation and common disinfectants such as ether and formaldehyde.

Genome product of influenza virus

(1) Hemagglutinin: HA is one of the glycoprotein protuberances of the influenza virus envelope and plays an important role in influenza virus infection and replication.

•  The surface of the host cell (including red blood cells) has a hemagglutinin receptor, and the influenza virus binds to it by hemagglutinin, so that the influenza virus can be adsorbed to the host cell membrane. Since the adsorption of red blood cells by influenza virus is characterized by red blood cell agglutination, hemagglutinin is named after it. After the influenza virus is adsorbed on the surface of the host cell, the fusion process between the viral envelope and the cell membrane is initiated, and the virus penetrates into the host cell membrane, and then enters into the host cytoplasm in the form of vesicles through the pinocytosis.
• In the low pH environment of vesicles, HA cleaves into HA-1 and HA-2 subunits, undergoes a conformational change, and the fusion sequence present at the amino acid terminus of HA-2 is exposed, activating the lytic polypeptide, so that The vesicle form enters the host cytoplasm and the viral nucleocapsid is released from the capsule.

(2) Neuraminidase (NA): NA is another glycoprotein protuberance of the influenza virus envelope. But the amount is significantly less than hemagglutinin. It cleaves the binding bond between the oligomeric polysaccharide and the terminal neuraminic acid residue (ie, N-acetylneuraminic acid, also known as citric acid). The hemagglutinin receptor on the surface of the host cell contains tannic acid coupled to the oligomeric polysaccharide. Neuraminidase has important biological biological significance for the degradation of tannic acid contained in it:

• Neuraminidase damages the sialic acid contained in the host cell surface receptor, allowing the influenza virus to be released from the infected cells, and releasing the extracellular flu virus to disaggregate and disperse from each other, thereby Conducive to its spread.
• The mucus of the respiratory tract also contains a citrate component. The lytic activity of the neuraminidase is such that the influenza virus breaks through the mucus and is prone to spread in the respiratory mucosa.

Because neuraminidase plays an important role in the replication of influenza virus, and the active site of neuraminidase is highly conserved in influenza A and B viruses. Therefore, many of the new anti-influenza drugs developed have NA as a target for drug effects.

(3) Nucleocapsid protein (RNP): a viral structural protein that together with viral RNA constitutes a nucleocapsid, including nuclear protein (NP) and three polymerase proteins (PB-1, PB-2, PA). All three polymerase proteins are synthesized in the host cytoplasm and then transferred to the nucleus. Among all structural proteins of influenza A and B viruses, PB-1 is the most homologous protein, and its function is responsible for the extension of viral mRNA synthesis initiation. PB-2 is a viral RNA-dependent RNA polymerase. Its function is to recognize and bind to the cap-like structure transcribed by the host cell polymerase II, and the cap-like structure can be excised from the host cell and ligated to the 5-end of the virus-specific mRNA. The cap-like structure is a primer for viral mRNA transcription, which initiates transcription of RNA. During post-transcriptional processing, PB-2 may be involved in the excision of the mRNA 5-terminal cap structure. The role of PA in viral RNA synthesis has not been fully elucidated and may be a kinase or an unwinding protein.

(4) Membrane protein (MA) is one of the structural components of the influenza virus envelope, including M1, M2. M1 contains 252 amino acids and is the most abundant polypeptide in virion. It has type-specificity and is one of the main basis for influenza virus typing. M1 may play an important role in progeny virus assembly while protecting ribonucleoprotein particles. M2 is a complete membrane protein containing 97 amino acids, found only in influenza A virus. M2 is abundantly present on the surface of infected host cells in the form of tetramers, but is rarely present in virions. Its function is a proton channel to control the pH in the Golgi cavity during HA synthesis and the acidification inside the vesicle during viral decapsulation.

The rapid variation of influenza virus mutations is a major feature of influenza viruses. Influenza virus mutations are mainly due to changes in the structure of HA and NA antigens, especially HA. This is because the antibody produced by the body against HA is a neutralizing antibody, so the influenza virus can effectively achieve immune escape by changing the antigenic properties of HA. Because its genome consists of multiple segments, the virus is prone to mutation. When the spontaneous point mutation of the genome is aggregated to a certain extent, it causes an antigenic drift. This genetic variation, which occurs to a lesser extent, occurs frequently in influenza A or B every year or every few years. If two different subtype strains infect cells and recombine their genomes, they can cause antigenic shifts, leading to the emergence of new serotypes. The mutations of HA and NA are continuously combined into new mutants. When the mutations make the immune barrier established by the original epidemic in the population no longer play an effective protective role, the mutants attack and invade the fully susceptible population. It caused an outbreak of the epidemic, which is an important cause of repeated epidemics. Significant mutations occur mainly in influenza A viruses, while influenza B viruses are much less common, while influenza C viruses generally do not.