The Medical Characteristics of the Orthomyxovirus (Influenza) Family

The name myxovirus was originally applied to influenza viruses. It meant virus with an affinity for mucins. Now there are 2 main groups-the orthomyxoviruses and the paramyxoviruses. All orthomyxoviruses are influenza viruses, isolated strains are named after the virus type (A, B, C), the host and location of initial isolation, the year of isolation and the antigenic designation of the hemagglutinin and neuraminidase. Eleven hemagglutinin antigenic subtypes and 8 neuramidase antigenic subtypes are designated. Both of these are glycoproteins under separate genetic control, and they vary independently. Examples of influenza designations follow: A/swine/New Jersey/76 (H1N1), previously (Hsw1N1), A/Brazil/78 (H1N1), B/Singapore/79, A/Bangkok/79 (H3N2).

Influenza

Influenza is an acute respiratory tract infection that usually occurs in epidemics. Three immunologic types of influenza virus are known: A, B, and C. Antigenic changes continually take place within the A group of influenza viruses and to a lesser degree in the B group, whereas influenza C appears to be antigen stable. Influenza A strains are also known for pigs, horses, ducks, and chickens (fowl plague). Some animal isolates are antigenically similar to the strains circulating in the human population.

Influenza virus type C differs from the type A and type B viruses; its receptor-destroying enzyme does not appear to be a neuraminidase, and its virion structure is not fully understood. The following descriptions are based on influenza virus type A.

Properties of the Virus

Structure

Influenza virus consists of pleomorphic, approximately spherical particles having an external diameter of about 110nm and an inner electron-dense core of 70nm. The surface of the virus particles is covered with 2 types of projections, or spikes approximately 10nm long possessing either the hemagglutinin or the neuramidase activity of the virus.

The RNA genome consists of 8 distinct pieces with an aggregate molecular weight of 2-4 X 10^6. Due to its divided genome, viruses of this group exhibit several biologic phenomena such as high recombination frequency, multiplying reactivation, and ability to synthesize hemagglutinin and neuraminidase after chemical inactivation of viral infectivity. Although viral RNA has not proved to be infectious, viral ribonucleoproteins appear to be so. This structure contains the virion-associated RNA-dependent RNA polymerase as well as the genome. Evidently, all messenger RNA is complementary to the virion RNA.

The results of hybridization studies on RNA have supported the immunologic grouping of the hemagglutins of the influenza A viruses. Similar studies of the neuramidase genes have been in agreement with N antigen subtype designations based on the results of serologic tests.

Reactions of Physical and Chemical Agents

Influenza viruses are relatively stable and may be stored at 0-4 degrees Celsius for weeks. The virus is less stable at -20 degrees Celsius than at +4 degrees Celsius. Ether and protein denaturants destroy infectivity. The hemagglutinin and CF antigens are more stable than the infective virus. Ultraviolet irradiation destroys infectivity, hemagglutinin activity, neuraminidase activity and CF antigen, in that order. Infectivity and hemagglutination are more stable at alkaline pH than at acid pH.

Animal susceptibility and Growth of virus

Human strains of the virus can infect different animals; ferrets are most susceptible senal passage in mice increases its virulence, producing extensive pulmonary consolidation and death. The developing chick embryo readily supports the growth of virus, but there are no gross lesions. Wild influenza viruses do not grow well in tissue cultures. In most instances, only an abortive growth cycle occurs, i.e, viral subunits are synthesized but little or no new infections progeny is formed. From most influenza strains mutants can be selected that will grow in cell culture. Due to poor growth of many strains in cell culture, initial isolation attempts should employ inoculation both of the amniotic cavity of the embryonated egg and of monkey cell cultures.

The process of infection begins by adsorption of the virus onto its receptor sites (neuraminic acid- containing glycoproteins). The hammagglutinin protein is involved in this reaction. The other spike protein, neuraminidase, can destroy the site. The virus particle is taken into the cell, where it is disrupted, causing a decrease in detectable virus shortly after infection intracellular synthesis of the viral RNA and protein then occurs. Viral RNA pieces are synthesized individually in the nucleus within 2-3 hours. All viral proteins are synthesized in the cytoplasm structural proteins bind to the cell membrane and are joined by the ribonucleoprotein at 8 hours, new virus particles bud through the membrane. Neuraminidase may be important in release of the completed virion.

In most influenza virus systems, non infectious particles capable of hem agglutination are produced. These particles, called “incomplete”, increase in number upon serial, high-multiplying passage of the virus. The incomplete particles are smaller and more pleomorphic than standard virus, and they interfere with replication of standard virus. They are known as defective interfering, or DI, particles been the largest Virus RNA piece is missing from such particles.

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