Specific Viral Families: Orthomyxoviridae

Orthomyxoviridae

The orthomyxoviruses are medium-sized, enveloped, (-)-sense RNA viruses that vary in shape from spherical to helical. Their genome is segmented into eight pieces. Orthomyxoviruses have an affinity for mucus. The influenza A and B viruses in this viral family are of particular medical importance to humans since they cause disease in humans.

Influenza Viruses

The influenza A virus is an orthomyxovirus that infects humans, birds, swine and horses. It causes pandemics of influenza (~10-20 years) and major outbreaks of influenza (virtually every year in various countries). The influenza B virus, on the other hand, appears to be specific to humans only. It causes major outbreaks of influenza, which occur less often as those caused by the influenza A virus.

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Diagram of the Influenza virus

Important Properties

    · Typically spherical (100nm in diameter).

    · Composed of a single stranded (-) sense RNA genome in eight segments, a helical nucleocapsid, and an outer lipoprotein envelope.

    · 3 polymerase polypeptides with each segment.

    · 5’ and 3’ end of all segments are highly conserved.

    · Virion contains RNA-dependent RNA polymerase, which transcribes the (-) sense RNA to mRNA. Thus, the genome is not infectious.

    · Viral envelope is covered with two different types of spikes—haemagglutinin (HA) and neuraminidase (NA).

    · The ratio of HA:NA is 5:1.

Haemagglutinin functions at the beginning of infection, whereas the neuraminidase functions at the end.

Haemagglutinin

    · Binds to the cell surface receptor (neuraminic acid, sialic acid) to initiate infection.

    · Target of neutralizing antibody.

Neuraminidase

    · Cleaves neuraminic acid (sialic acid) to release progeny virus from the infected cell.

    · Degrades the protective layer of mucus in the respiratory tract, thus enhancing the ability of the virus to infect the respiratory epithelium.

Pathogenesis

    · After the virus has been inhaled, the neuraminidase degrades the protective mucus layer, allowing the virus to gain access to the cells of the upper and lower respiratory tract.

    · The infection is limited primarily to this area because the HA receptors have a specific affinity for the epithelial cells of the respiratory tract.

    · Despite systemic symptoms, viremia rarely occurs.

    · The systemic symptoms are due to cytokines circulating in the blood.

    · There is necrosis of the superficial layers of the respiratory epithelium.

    · Immunity rests mainly upon secretory IgA in the respiratory tract.

    · IgG is also produced and confers protection against future infections.

    · Innate resistance also plays a role in immunity—a mucus blanket and cilia helps to trap and expel the influenza virus out of the respiratory tract.

    · Cytotoxic T cells also play a protective role.

    · Immunocompromised patients especially prone to secondary infection such as pneumonia.

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Clinical Features

    · After an incubation period 24-48 hours, fever, myalgias, headache, sore throat, and cough develop suddenly.

    · Severe myalgias (muscle pains) coupled with respiratory tract symptoms are typical of influenza.

    · Vomiting and diarrhoea are rare.

    · Symptoms usually resolve spontaneously in 4-7 days.

Differentiating Between the Common Cold and Flu

Laboratory Diagnosis

    · Nasal/throat washings or swabs; sputum.

    · Virus culture in MDCK cell line or chick embryo.

    · Direct ELISA for Haemagglutinin

    · PCR assay

Transmission and Epidemiology

    · Virus is transmitted by airborne respiratory droplets.

    · Ability of influenza A virus to cause epidemics is dependent on antigenic changes in haemagglutinin and neuraminidase.

    · Influenza infections are found all year round.

    · In the northern hemisphere, influenza occurs primarily in the winter months.

    · In the southern hemisphere, influenza occurs primarily in the winter months of June through August.

    · Few serotypes circulating simultaneously.

    · Epidemics and pandemics occur when the antigenicity of the virus has changed sufficiently that the pre-existing immunity of many people is no longer effective.

    · The antigenicity of influenza B virus also varies but not as dramatically or as often.

Antigenic Drift vs. Antigenic Shift

Antigenic Drift	Antigenic Shift
Minor change in genome.	Major change in genome.
Occurs in both Influenza A and B viruses.	Occurs in only Influenza A virus.
Point mutation in the genetic code of surface antigens.	Gene reassortment, where entire segments of RNA are exchanged, each one of which codes for a single protein (e.g. haemagglutinin).
Results in a new strain.	Results in a new subtype.
Happens all the time.	Happens occasionally.
Responsible for epidemics.	Responsible for pandemics.

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Strain Naming Convention

Strains of influenza are named as follows:

(Influenza Type)/(Animal species (omitted if human)/(Place of Isolation)/(Number of Isolates)/(Year of First Isolation)(H and N subtypes)

Example: A/Texas/36/91/(H1N1)

Control and Treatment

    · The main mode of prevention is the vaccine, which consists of killed influenza A and B viruses. It is rendered useless by antigenic shift/drift—therefore, the vaccine is usually reformulated every year to contain the current antigenic strains.

    · Antiviral drugs are used to treat influenza. This includes receptor analogues, transcriptase inhibitors, reverse transcriptase inhibitors, protease inhibitors and neuraminidase inhibitors etc.

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