Orthomyxoviruses

GENERAL CONCEPTS:

The Orthomyxoviruses are composed of one genus and 3 types; A, B and C.
The disease caused by these viruses, influenza, is an acute respiratory disease with prominent systemic symptoms despite the fact that the infection rarely extends beyond the respiratory tract mucosa.
Type A is responsible for periodic worldwide epidemics; types A and B cause regional epidemics during the winter.
The recurring pattern of the influenza viruses is due to their ability to exhibit variation in surface antigens. Two phenomenon account for this variability:
1. Antigenic drift is due to mutations in the RNA that leads to changes in the antigenic character of the H and N molecules. Antigenic drift involves subtle changes that may cause epidemics but not pandemics.
2. Antigenic shift is due to rearrangement of different segments of the viral genome that produces major changes in the antigenic character of the H and N molecules. Antigenic shift usually occurs in animal hosts and is responsible for producing both epidemics and pandemics.
Influenza epidemics have been documented since 1173 AD; a pandemic in 1918 was responsible for 20 million deaths worldwide.
The table outlines some of the differences between the three types of influenza virus:

DISTINCTIVE PROPERTIES:

Orthomyxoviruses contain a single stranded, negative RNA genome divided into 8 segments.
The viruses have a lipid bilayer envelope with surface glycoproteins (hemagglutinin and neuraminidase)
There are 3 viral antigens of importance: the nucleoprotein antigen that determines the virus type (A, B or C), the hemagglutinin (H) antigen, and the neuraminidase (N) antigen. The H and N antigens are variable. There are about 13 different H antigens and 9 different N antigens found in birds. This provides a total of 117 (13 x 9) possible combinations, 71 of which have been observed. There are only about 3 combinations that affect humans, however.
Viral attachment is mediated by the hemagglutinin. The virus enters host cells by pinocytosis and uncoating occurs by fusion of the viral envelope with the membrane of the vacuole. The RNA is capped and replication proceeds in the nucleus. The progeny are released by budding and cell death ensues.
The segmented genome of the influenza virus allows rearrangements to occur in simultaneously infected cells. This accounts for the periodic appearance of new variants. The new variants are responsible for the process of antigenic shift.

PATHOGENESIS:

Transmission of disease is airborne. The viruses deposit in lower respiratory tract, their primary site is the tracheobronchial mucosa.
Neuraminidase produces liquefaction, which leads to viral spread.
Respiratory symptoms include a cough, sore throat and nasal discharge. There is no viremia but systemic symptoms such as fever and muscle aches do occur.
The extent of respiratory tract cell destruction is a probable factor in the disease.
Severe complications include pneumonia (viral or bacterial).

HOST DEFENSES:

Interferon is one non-specific defense but antibody is the prime defense. IgA is produced in the upper respiratory tract and IgG is produced in the lower respiratory tract. These antibodies are directed primarily against the hemagglutinin and neuraminidase. Cell-mediated (i.e. CTL) defenses are important in recovery.

EPIDEMIOLOGY:

Number and percentage of respiratory specimens testing positive for influenza,
by type, subtype, surveillance week, and year; CDC.gov

Influenza displays a typical pattern: school children bring the disease home and infect siblings and parents.
Epidemics usually last from 3-6 weeks and the highest attack rates are for 5-19 year olds (generally Type A).
Every winter, the recurring population susceptibility is due to changes in the surface antigens; major changes are referred to as antigenic shift. These changes are responsible for pandemics and they result from rearrangement of the viral genome segments. Minor changes are called antigenic drift and these are responsible for many epidemics. They result from mutation in the viral RNA. Antigenic drift occurs every 2-3 years while antigenic shift only occurs every 10 years.
The table illustrates this pattern for pandemics due to antigenic shift. Notice the 10 year span between pandemics and the 30 year (generational) span between recurrence of the same antigenic character:

DIAGNOSIS:

Clinical: Influenza usually displays a sudden onset with fever, malaise, headache, muscle aches, sore throat, cough and rhinorrhea, generally in winter. The presence of disease in the community (i.e. epidemiology) is helpful in diagnosis.
Laboratory: Serology on the patient's serum can be performed or the viruses may be isolated in chick embryos if necessary.

CONTROL:

Sanitary: Avoid contacts.
Immunological: Every year, inactivated vaccines are prepared using the most likely types and antigenic characters expected for any particular season. These vaccines are given parenterally in the fall, primarily for those at risk (older persons or those with chronic disease). Protection against disease is variable (50-90%).
Chemotherapeutic: The drug amantadine HCl can be used for influenza type A but not type B in patients with other disease conditions. Generally, however, pain relievers (e.g. acetaminophen) are more generally employed.