Influenza is an acute viral infection of the respiratory tract which is considered to be one of the life-threatening infectious diseases. In certain countries, seasonal influenza affects up to 40% of the population every year, with the worldwide death toll of 500 million people. The virus can be transmitted by direct contact with infected individuals, via contaminated objects (also called fomites) and by inhalation of virus-laden aerosols.
An unexpected emergence of a new and highly virulent influenza virus strains can result in a world-wide pandemics with high morbidity and mortality – such as the “avian flu” in 1997 and “swine flu” in 2009. Throughout history, some influenza pandemics were extremely devastating; for example, the 1918–1919 influenza pandemic has killed more people in absolute numbers than any other disease outbreak in history.
Structure of the influenza virus
Human influenza viruses are single-stranded RNA viruses with a pleomorphic appearance and a diameter range between 80 to 120 nanometers. They are members of the family Orthomyxoviridae, which consists of the genera Influenzavirus A, B and C, as well as the Thogotovirus, Isavirus and Quaranjavirus (in animals). The influenza virion – an infectious particle of the virus – is roughly spherical.
The virus is enveloped, which means that the outer part contains a lipid membrane taken from the host cell where the virus multiplies. In the lipid membrane there are glycoproteins (consisting of a protein linked to sugars), known as HA (hemagglutinin) and NA (neuraminidase). These are the structures that determine the subtype of influenza virus (for example, A/H1N1).
HA and NA are especially important in the immune response against the virus; hence they are also called antigenic determinants. Antibodies (proteins that our organism produces in order to combat infections) against these spikes may protect against infection. The NA protein is the target of the antiviral drugs zanamivir (Relenza) and oseltamivir (Tamiflu). The M2 protein is embedded in the lipid membrane as well, which is the target of other “flu” antivirals – amantadine and rimantadine.
Beneath the lipid membrane, a viral protein called M1 (or a matrix protein) is found. This protein forms a shell, thus giving rigidity and strength to the lipid envelope. The interior of the virion contains another protein called NEP, which recruits M1 to the viral ribonucleoprotein to mediate nuclear export.
Inside the virion are also the viral RNAs – 8 of them for influenza A and B viruses, and 7 for influenza C. These represent the genetic material of the virus and code for one or two proteins. Each of those RNA segments consists of RNA joined with specific proteins (PB1, PB2, PA, NP). These RNA segments are the genes of influenza virus.
How the virus causes a disease
In order to cause a disease, a virus must first enter the cell. Viruses are obligate intracellular parasites, which means that they cannot reproduce outside of a cell. After the virion attaches to sialic-acid containing receptors at the surface of a target cell, the resulting virus-receptor complex is taken into cells by endocytosis – a process which cells normally employ to take up molecules from the extracellular fluid.
When the pH in the virus-containing endosome drops, the viral HA protein undergoes a conformational rearrangement, causing a fusion of the endosomal membrane with the viral envelope. That represents a key event in releasing the viral RNAs into the cytoplasm. They are subsequently transported into the cell nucleus where viral RNA replication happens, and the infectious particles are released via budding from the plasma membrane. The time from entry to production of new virus is 6 hours on average.
The main targets of the influenza virus are the columnar epithelial cells of the respiratory tract, i.e. trachea, bronchi and bronchioles. Viral replication in combination with the immune response to infection results in the destruction and loss of the mucosal epithelial cells. Human influenza leads to complex cytopathic effects due to down-regulation of host cell protein synthesis and apoptosis (programmed cell death).
Infectivity of influenza virus particles depends on the pH, temperature and salinity of the water, as well as the UV irradiation. At 4 °C, the half-life of infectivity is between 2 and 3 weeks in water. Survival under normal environmental conditions is shorter due to the conformation of the lipid bilayer. Infectivity of the virion is easily inactivated by all alcoholic disinfectants, chlorine, aldehydes and temperature above 70 °C.
- Nicholson KG, Webster RG, Hay AJ. Textbook of Influenza. Blackwell Science, Oxford, 1998.
- Lamb RA, Krug RM. Orthomyxoviridae: The viruses and their Replication. In: Fields Virology fourth edition, Knipe DM, Howley PM eds, Lippincott, Philadelphia 2001, pp 1487-1531.