In this article we will discuss about the replication of influenza viruses.
Influenza virus is transmitted from infected mammals through the air by sneezing. Sneezing creates aerosols which consist of several virus particles. Besides, influenza is also transmitted by saliva, nasal secretions, blood and faeces. Moreover, it also spreads through droppings of infected birds.
These bodily fluids or contaminated surfaces cause infection after making contacts. Influenza viruses can remain infectious for about one week at human body temperature. It remains viable over 30 days at 0°C and indefinitely at very low temperatures. Disinfectants and detergents easily inactivate the virus.
Coming in the contact of host cell surface, virus particles bind to a cell. Viral binding to host cell is initiated by interactions between its hem-agglutinin glycoprotein and sialic acid sugars present on the surfaces of epithelial cells in the lung and throat (Fig. 17.36, step 1). Virus enters inside the cell through endocytosis.
The endosome encloses the viral particle. In the acidic endosome, part of viral haemagglutinin protein fuses with the membrane of the vacuole consequently, the viral RNA (vRNA), accessory proteins and RNA-dependent RNA polymerase are released into the cytoplasm (step 2). These proteins and vRNA form a complex that is transported into the nucleus, where transcription of complementary (+) sense vRNA is started by RNA- dependent RNA transcriptase (steps 3a and b).
The vRNA either remains in the nucleus, or is exported into the cytoplasm translated (step 4). Newly synthesized viral proteins are either transported back into the nucleus to bind vRNA and form new viral genome particles (step 5a), or secreted through the Golgi bodies onto the cell surface (in the case of neuramimdase and hem-agglutinin, step 5b).
In the host cell the other viral proteins carry out several functions such as degradation of cellular mRNA, use of released nucleotides for vRNA synthesis and also inhibition of translation of mRNAs of the host cell.
Virions are assembled after accomplishment of genome replication and protein synthesis. The (-) vRNAs that is to act as genome, RNA-dependent RNA transcriptase, and other viral proteins are assembled into a virion. Hem-agglutinin and neuraminidase molecules cluster into a bulge of the cell membrane. The vRNA molecules and viral core proteins are transferred from the nucleus and enter the protrusion of the membrane (step 6).
The mature virus buds off from the cell in a spherical structure formed by the host’s membrane. The haemagglutinin and neuraminidase get attached to the surface of this membrane (step 7). Now, the viruses remain attached to the cell through hem-agglutinin. When the neuraminidase has cleaved sialic acid residues of the host cell, the mature viruses are detached and released from the cell. The host cell dies, after the release of new influenza virus.
Since there is no RNA proofreading enzymes, the RNA-dependent RNA transcriptase makes a single nucleotide insertion error roughly every 10 thousand nucleotides. This is about length of the influenza vRNA. Therefore, almost every newly formed influenza virus contains mutation in its genome.
If more than one variety of influenza viruses has infected the same cell, the separation of the genome into eight separate segments of vRNA allows re-assortment of the genes. It is called as antigenic shift. Because the altered genome segments packaged into viral progeny confers new behavior in infecting the new host species or protective immunity of host populations to its old genome.