In the last text, it was discussed the capacity of H5N1 of infecting a number of hosts and causing very harsh symptoms, causing deaths in over 50% of the recorded human cases. Despite this, its transmission from person to person seems to be well limited. Now we will see its characteristics that contribute to this.

acido_sialico

Types of sialic acid. Source: Reference 2.

ResearchBlogging.orgAs already seen before, what determines the type of cell to be infected by the influenza is the Hemagglutinin (HA), due to its preference for the sialic acid of the cell. But it is not any sialic acid that can be used. The recognition by HA depends on the position of the carbon that makes the bond between the acid and the molecule to which it is attached. The bond receives this name because of this position. In birds and mammals, occur especially in the sialic acids α2,3 and α2,6

In our respiratory tract, the α2,6 acid predominates in the upper part, region of the nasal cavity and the pharyngeal cavity, while the α2,3 occurs especially in the lower respiratory tract, in the alveoli, bronchia and other lung cells. Human virus has a hemagglutinin with higher affinity for sugars that end in an α2,6 sialic acid and therefore, can replicate in the upper tract and spread more easily through cough and sneeze. Bird virus, however, have an affinity for sugars that end with α2,3, the predominants in the digestive system of birds, where the virus replicates. – Although in mammals the influenza is predominantly a respiratory virus, in birds, it is predominantly an intestinal virus.

Colorized_transmission_electron_micrograph_of_Avian_influenza_A_H5N1_viruses

Influenza H5N1 shown in yellow, seen through an electronic and artificially colored microscope. Source: Wikimedia.

Therefore, when bird viruses like H5N1 infect humans, they end up bonding and replicating better in the lower respiratory tract. This explains the observed severe symptoms in the lungs, as well as the difficulty of H5N1 of being transmitted between humans. It replicates less in places that make easier its spreading, such as nasal cavities. [1]

Despite the elegance of the argument, α2,3 receptors have been found in the upper respiratory tract and α2,6 in the lower respiratory tract. What raises doubts on how significant this difference can be in order to explain the low transmission of the virus. [2]

Another important property of this virus also concerns hemagglutinin, more precisely its maturity. After being expressed by the cell, hemagglutinin still has to be digested by an external protease to work. Only the fragmented hemagglutinin in pieces can link the virus to the next cell, completing the infection, as already observed. Generally, what carries out this digestion is a protease produced in the mucus of the respiratory tract, restricting the virus to this environment.

However, the Hemagglutinin of H5N1 and other highly pathogenic viruses have a cleavage region with several basic aminoacids, which allows the digestion of the hemagglutinin by several proteases, not only those found in our respiratory tract. Like the furin protease, which occurs in almost any type of cell. Then, the influenza HPAI is able to infect and replicate in various other tissues and cause a systemic infection. [3]

Other characteristics are necessary for a virus to be highly pathogenic, such as the capacity to replicate its RNA efficiently in various cells. This occurs because the replacement of the low pathogenic viral hemagglutinin cleavage site by another site with more basic aminoacids, common in high pathogenic influenzas, was not enough for the virus to cause more severe symptoms in model animals, although it had replicated more efficiently. [4]

Constant monitoring of the virus and preventive preparation by the government is necessary to ensure that, in the case of the appearance of a highly pathogenic lineage successfully transmitted between humans, the measures to contain them are taken quickly before greater damage is caused. The possibility of the H5N1 undergoing a rearrangement with virus already adapted to humans, improving its transmission efficiency or providing dangerous properties, is very disturbing.

Due to the severity of its symptoms, diversity of hosts, circulation in animals close to humans and with dangerous properties, domestic and wild birds have been monitored since the appearance of H5N1. This threat is also the reason for the stock of antivirals, the expansion of vaccine production capacity and the conduction of diagnostic tests.

Many of these preparations are being used in this epidemic of 2009; in the USA alone over 50 thousand cases of Influenza A (H1N1), were diagnosed, a new number of tests. This amount of antivirals has never been readily available for use before. The same occurs for the quantity of vaccine doses being produced. Whatsoever as these measures have been taken against H5N1, they are effective for any Influenza. Prevention always yields returns.

Sources:

[1]van Riel, D. (2006). H5N1 Virus Attachment to Lower Respiratory Tract Science, 312 (5772), 399-399 DOI: 10.1126/science.1125548
[2] Zambon, M. (2007). Lessons from the 1918 influenza Nature Biotechnology, 25 (4), 433-434 DOI: 10.1038/nbt0407-433
[3] Steinhauer, D. (1999). Role of Hemagglutinin Cleavage for the Pathogenicity of Influenza Virus Virology, 258 (1), 1-20 DOI: 10.1006/viro.1999.9716
[4] Stech, O., Veits, J., Weber, S., Deckers, D., Schroer, D., Vahlenkamp, T., Breithaupt, A., Teifke, J., Mettenleiter, T., & Stech, J. (2009). Acquisition of a Polybasic Hemagglutinin Cleavage Site by a Low-Pathogenic Avian Influenza Virus Is Not Sufficient for Immediate Transformation into a Highly Pathogenic Strain Journal of Virology, 83 (11), 5864-5868 DOI: 10.1128/JVI.02649-08