Biological Properties, Pathogenesis and Pathology of the Influenza Virus

Biological Properties, Pathogenesis and Pathology of the Influenza Virus

HemagglutininAll strains of influenza virus agglutinate erythrocytes from chickens, guinea pigs and humans and-unlike paramyxo viruses-agglutinate erythrocytes from many other species as well Agglutination of red blood cells occurs when the hemagglutinin interacts with a specific receptor on the red blood cell membrane. This receptor is a glycoprotein that contains sialic acid. This glycoprotein serves both as the receptor site for the hemagglutin and as the substrate for the viral neuraminidase, Cleavage of the glycoprotein by the enzyme dissociates the virion from the red cell, resulting in spontaneous elution. After elution, the cell receptors are destroyed and hence can no longer be agglutinated with fresh virus, however, the eluted virus can reattach and agglutinate additional cells.

Group antigenAll influenza A virus strains share a common antigen, distinct from those of influenza B and C. This soluble (S) antigen is found in the medium from infected cell cultures and is a component of the ribonucleoprotein of the virus it can be identified by CF. Antibody to this nucleoprotein antigen does not induce resistance to the virus in humans. The other internal proteins and the RNA polymerase also have group-specific antigenic activity.

Specific antigenThe infections virus particles induce in animals the development of virus-neutralizing and other antibodies, and the inoculated animals become resistant to infection, Influenza virus administered in large amounts is toxic. The effect is apparently associated directly with the virus particles and can’t be prevented by specific antibody. Virions contain 2 subtype or strain-specific antigens, the hemagglutinin and the neuraminidase. The hemagglutinin is the prinicipal specific envelope antigen and differences in this antigen among strains of virus can be shown by HI tests. Antibody to the hemagglutinin neutralizes virus and is a protective mechanism.

Neuraminidase is antigenically distinct from the hemagglutinin and is governed by a separate gene (RNA fragment); hence, it can vary independently of the hemagglutinin. The antigens of the hemagglutinin and the neuramidase of the virus are the basis for classifying new strains. Antibody against the neuraminidase does not neutralize the virus, but it modifies the infection, probably by its effect on the release of virus from the cells. The antibody against the neuramidase occurs in sera of humans who experience infection. The presence of antineuraminidase antibody results in marked protection against disease.

RecombinationThe multisegment nature of the influenza virus genome allows recombination to occur with high frequency by reassortment between orthomyxoviruses of the same group. The RNA fragments of different influenza A viruses migrate at different rates in polyacylamide gets. Similarly, the polypeptides of different influenza A viruses can be differentiated. Thus, using 2 different parental viruses and obtaining recombinants between them, it is possible to tell which parent donated which RNA fragments to the recombinant, these techniques enable rapid and more complete analysis of recombinants that emerge in nature.

Pathogenesis and pathologyThe virus enters the respiratory tract in airborne droplets. Viremia is rare. Virus is present in the nasopharynx from 1-2 days before to 1-2 days after onset of symptoms. The neuraminidase lowers the viscosity of the mucous film in the respiratory tract, laying bare the cellular surface receptors and promoting the spread of virus-containing fluid to lower portions of the tract. Even when neutralizing antibodies are in the blood they may not protect against infection.

Antibodies must be present in sufficient concentration at the superficial cells of the respiratory tract. This can be achieved only if the antibody level in the blood is high or if antibody is secreted locally. Inflammation of the upper respiratory tract causes necrosis of the ciliated and goblet cells of the tracheal and bronchial mucosa but does not affect the basal layer of epithelium. Interstitial pneumonia may occur with necrosis of bronchiolar epithelium and may be fatal. The pneumonia is often associated with secondary bacterial invaders: staphylococci, pneumococci, streptococci and Haemophilus influenzae.