Orthomyxoviridae family comprises of unique classes of viruses (i.e. Orthomyxoviruses) that causes highly contagious respiratory disease known as influenza or viral flu in humans. Orthomyxoviruses viruses are zoonotic disease agents transmissible from animals to humans. The Orthomyxoviruses are distributed worldwide and they cause respiratory infections in both humans and animals. Orthomyxoviruses have a ss(-)RNA genome, and they have a helical nucleocapsid. They measure between 80-120 nm in diameter. They replicate in the nucleus. Orthomyxoviruses are enveloped viruses. Though the synthesis of the RNA genomes of RNA viruses occurs in the cytoplasm; that of the Orthomyxoviruses are known to occur in the nucleus of the cell, and this is possible because they contain or harbour an RNA-dependent RNA polymerase (as aforementioned) which convert their ss(-)RNA genome to a ss(+)RNA genome.
Orthomyxoviruses are released from the host cell via the cytoplasmic membrane by the process of budding. There are five genera of viruses that make up the Orthomyxoviridae family; and three of these viral genera cause significant human infections. Influenzavirus A, Influenzavirus B, Influenzavirus C, Thogotovirus and Isavirus are the five genera that make up the orthomyxoviridae family. Influenzavirus A (which comprise of influenza A), Influenzavirus B (which comprise influenza B) and Influenzavirus C (which comprise influenza C) are the genera of Orthomyxoviridae family that cause infections in humans. Thogoto virus (found in the Thogotovirus genera) and infectious salmon anemia virus (found in Isavirus genera) cause infections in mammals and fish respectively. The influenza viruses (especially influenza A and B) are important human pathogens that are primarily transmitted via the respiratory tract or route in aerosols of infected persons. Influenza viruses have continued to cause epidemics amongst human population; and this is due in part to the reassortment of the genetic makeup of the organism. And this mutation or gene reassortment in influenza viruses has impacted negatively on the development of long-lasting immunity against the pathogen due to the continuous change in the structural and genetic makeup of the organism.
When the RNA genome of two genetically distinct strains of influenza virus that infect the same cell or organism are re-assorted, a biological process known as antigenic shift occurs; and this leads to the production of a new virus that is different from that of the two original virions from which it was initially developed from. Influenza viruses also undergo antigenic drift in their quest to mutate into new virions. Antigenic drift occurs when the protein structure of the virus (especially the neuraminidase and haemagglutinin) undergoes mutation to produce newer virions that will not be recognized by protective antibodies produced by the host’s immune system. Antigenic drift and antigenic shift are mainly responsible for the continuous emergence of new epidemics of influenza virus because these processes lead to the formation of novel strains of the virus. Neuraminidase (NA or N) and haemagglutinin (HA or H) are the two important proteins found on the surface of influenza virus; and they are used in the typing of the organism especially in the face of outbreak of disease caused by influenza virus. HA and NA are the two major antigens of influenza viruses.
While HA is mainly involved in the attachment and fusion of influenza virus to the host cell, NA basically aids in the release of the virion from the cell. There are several serotypes or subtypes of influenza viruses, and these have been classified based on their HA and NA variations. Influenza viruses are mainly reserved in animals inclusive of birds from which human infections have also occurred. The H5N1 influenza virus that caused influenza outbreaks in parts of Asia, Europe and Africa is mainly transmitted from birds to humans; and human to human transmission of this particular strain has not been recorded but likely. (The first outbreak of the H5N1 influenza virus infection known as “Avian Flu” occurred in poultry farms in Hong Kong in 1997; and human outbreaks of avian flu have been recorded). The virus replicate in the mucosa of the nasopharynx where they cause pharyngitis. The incubation period of the disease is between 2-3 days; and the infection can reach the lungs where pulmonary infections also occur.
The clinical symptoms of infections caused by the influenza viruses include fever, headache, cough, sore throat and nasal congestion. Secondary bacterial infections can occur in influenza infections; and these infections which occur mainly in the lungs are caused by Streptococcus and Haemophilus species. However, secondary bacterial infections due to influenza are common amongst the immunocompromised host and people who are seriously ill. Flu is usually the general name used to describe viral infections caused by influenza virus. But the infection is sometimes confused with common cold and other bacterial respiratory diseases which present with similar symptoms. Proper clinical and laboratory diagnosis are critical for the effective treatment of flu caused by influenza viruses. Antiviral therapy such as the use of amantadine (a synthetic amine and a viral uncoating blocker) is available for the treatment of flu caused by influenza virus. And since the organism is a genetically variable viral pathogen (as exemplified by their antigenic drift and antigenic shift), effective vaccination and prophylaxis should be administered to vulnerable groups of the human population.
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