Influenza Virus

Categorization
Class: Orthomyxovirus
Genome: RNA Virus, Negative ssRNA Virus, Segmented Virus Structure: Enveloped Virus, Helical Virus
Virology
  • Overview
    • The Influenza Virus envelope possesses two important proteins, Hemagglutinin and Neuraminidase, which are critical for viral replication.
  • Hemagglutinin (HA)
    • Hemagglutinin is the viral envelope protein which mediates attachment of the virus to host cells. HA appears to specifically interact with sialic acid residues present on host cell membrane proteins. The protein derived its namesake due to its ability to aggregate erythrocytes which also possess sialic acid residues. Neutralizing antibodies to HA are the primary source of immunity to influenza virus.
  • Neuraminidase (NA)
    • During egress of virus, the HA protein of a freshly shed virus often attaches to the sialic acid residues on the infected cell, thus tethering the shed virus and preventing effective spread. The neuraminidase envelope protein cleaves sialic acid residues during egress, thus untethering shed virus. Neutralizing antibodies to NA contribute to immunity to influenza virus.
Epidemiology
  • Overview
    • Influenza infections (AKA: The Flu) are common throughout the world but occasionally can spread in a pandemic pattern. Pandemic and non-pandemic spread of influenza can in large part be explained by the replicative features of the virus together with the host immune response. As described above, host immunity depends on neutralizing antibodies to the HA and NA viral envelope proteins; however, there are many different subtypes of the virus which possess radically different serotypes of HA and NA. During non-pandemic periods, immunity to the predominant influenza virus subtypes circulating through the world is spread relatively evenly among the world population, thus preventing the occurrence of a pandemic
    • Two questions now arise: How can the influenza virus continue to exist in the world given increasing population-wide immunity to the predmoninant subtypes and how can pandemics occur? The theories of Antigenic Drift and Antigenic Shif have been developed to answer these questions.
  • Antigenic Drift
    • Antigenic Drift refers to the gradual change of HA and NA structure due to randomly occurring point mutations as the virus replicates. The slow accumulation of mutations gradually changes the antigenic properties of HA and NA and renders previously developed neutralizing antibodies ineffective. Because the changes to HA and NA is slow (i.e. drifting), this allows influenza virus to continue to exist throughout the world but does not allow for rapid pandemic events.
  • Antigenic Shift
    • The influenza virus genome is divided into eight segments with HA and NA encoded on different segments. Some influenza subtypes primarily infect animals, especially birds, and thus there will be little to no immunity to their encoded HA or NA in the world population. On very rare occasions a single individual may be infected with two influenza viruses of radically different subtypes (e.g. One subtype that primarily infects humans and one that primarily infects animals). If a single cell becomes doubly-infected, hybrid viruses may become packaged which contain an HA from one virus and an NA from another virus. The "Antigenically Shifted" hybrid virus will thus possess either an HA or an NA to which there is little to no immunity in the general world population, allowing for rapid, uncontrolled spread of the hybrid virus in a pandemic pattern.
Pathogenesis
  • Influenza virus appears to exclusively infect cells of the respiratory tract and does not spread systemically. It primarily infects ciliated cells of the columnar respiratory epithelium and results in their death. The pathology associated with viral infection significantly decreases pulmonary immunity and thus substantially increases the risk of a secondary pulmonary bacterial infection.
Clinical Consequences
  • Influenza is characterized by the rapid onset of constitutional symptoms such as fever, headache, myalgia, and chills as well as a pharyngitis and cough. Constitutional symptoms usually subside within 4-5 days although the respiratory symptoms may last for a week or longer. When infection is uncomplicated, most patients return to normal health rapidly.
Complications
  • Complicated courses of influenza are more common in those with pre-existing chronic diseases as well as the elderly and in children. The primary complication of Influenza is an atypical community-acquired pneumonia. Pneumonia due to the influenza virus itself (Primary Influenza Pneumonia) is rare but when it does occur is quite severe. Much more commonly, reduced pulmonary immunity following influenza infection results in a secondary bacterial pneumonia usually due to Streptococcus pneumoniae, Staphylococcus aureus, or Haemophilus influenzae. In these patients, recovery from the influenza infection is followed in a few days by a bacterial pneumonia.
Treatment