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.

http://www.ifpma.org/Influenza/content/images/diagram_virus.jpg

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.

http://www.influenzareport.com/ir/images/image27.jpg

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.

https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiHqTazCXYaCPS7IC_6LrvBUpxQD7rlkXoTLlVRH5hb8c9mTJJFJLa6qQVqFiE3UTo_NdM4ZfFb7EK5O5TmZoiXuJh8QYoS4fs0kaK6yw6TxzUIzffq6PoKdZQdQqKMPCCkJUj2Bg_7Fxiz/s1600-h/aaaa.jpg

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.

http://www.pyroenergen.com/articles/images/tamiflu.jpg

Specific Viral Families: Picornaviridae

Picornaviridae

Picornaviruses are named for their small (“pico” + “RNA” = picorna) size. Nevertheless, they sure do have a massive and diverse array of viruses – over 100 serotypes! These viruses can even be traced all the way back to Ancient Egyptian records of polio epidemics, but are still around and cause a menagerie of diseases today.

Unique features, Morphology and Genome

Ø    Picornaviruses contain positive sense, single-stranded RNA that is approximately 7-8 kilobases long. 

Ø    The genome is monopartite  and polyadenylated at the 3’ end, but has a VPg protein at the 5’ end in place of a cap. 

Ø    The viral RNA is infectious and replication takes place in the cytoplasm. 

Ø    The virus has an IRES (Internal Ribosomal Entry Site) which distinguishes it from many other RNA viruses. 

Ø    The virus is naked with an icosahedral capsid. 

Ø    The triangulation number is 3, while the capsid has four unique proteins: VP1, 2, 3, and 4.

Ø    The capsid is one of the smallest of all viruses with a diameter of only 27-30nm.

Ø    Translation and cleavage of viral polypeptides produces eleven distinct proteins.

One example of a Picornaviridae virus is Rhinovirus.

 

With as many as more than 100 serotypes, rhinoviruses are transmitted through the respiratory route and replicate in the nose (“rhino”).  The many serotypes are then divided into “major” and “minor” groups and all cause a similar syndrome – the “common cold.”  The large number of serotypes allows many rhinovirus infections to occur in one person over time, since immunity only develops for one serotype and each newly acquired rhinovirus causes a new “cold.”  About half of all colds can be attributed to rhinoviruses, particularly those that occur in the winter.

Pathogenesis includes an Upper Respiratory Tract infection with a short incubation period of 2 to 3 days. Production of the endogenous IFN (Interferon) will help battle the virus to protect the body. IgA (a type of immunoglobulin present in blood and body secretions which may aid in fighting infections) is then locally synthesized, though it will degrade with time. However, our serum IgG (memory cell of immune system) would confer lifetime immunity! 

And how would you know that you’ve been infected by rhinovirus?

 Symptoms include, a watery nasal discharge, congestion, sneezing and little or no fever. 

A lab diagnosis of this virus will include culturing the virus, nasal washings, EIA and PCR. 

This epidemic occurs practically throughout the year, albeit there are a few serotypes circulating simultaneously! This is most probably due to the fact that the virus is abundant in nasal discharge. 

How does one control this “common cold” then? 

Well, you could wash your hands regularly, avoid touching your eyes or nose. If you happen to sneeze into a tissue, be sure to discard it right after! You might also want to avoid people who have a cold! Or, if you are the one with the cold, do stay at home! This will ensure that other people would not be affected! 

Rhino Virus