September 8, 2009
In the previous text, I addressed why it is difficult to develop antivirals, here we will understand the characteristics of the influenza virus that worries us.
Where do viruses come from and what makes them more or less dangerous?
The virus that infects us may already be with us during our evolutive history, or have recently come from other animals. HTLV for instance, has already infected the common ancestor between humans and chimpanzees before our divergence. Generally, these viruses hardly cause severe diseases. They and their hosts have had enough time to reach a point where, although virus can replicate and infect, it does not debilitate the carrier to an extent that reduces its chances of being transmitted.
Other viruses can circulate only in humans; however, they must have been transmitted by animals a long time ago. It appears to be the case of smallpox, which was transmitted to us by cows or camels around 10000 B.C., but lived with us long enough for people more resistant to the disease to be selected. This explains the enormous mortality of the Incas and of other people of the Americas that had never been exposed, before the arrival of the Spanish people that lived with the virus for thousands of years. Moreover, the death of so many Incas because of smallpox shows what happens when a new virus infects humans.
The virus that kills a large percentage of infected persons, such as the Marburg or Ebola, both filoviruses that cause terrible hemorrhagic fevers, are generally viruses that were recently transferred from animals to humans. In some cases they kill half the number of sick people. This mortality shows that the virus is still not adapted to the human host. When it enters a person, it causes so much damage, and so fast that the transmission to the next victims is affected. As much as we become impressed with the symptoms, such as collapse of organs and bloody vomit, this makes it possible to recognize an infected person and isolate that person.
The fruit-eating bats Rousettus aegyptiacus, considered natural hosts of the Marburg, show how a well-established virus would be like. The isolated virus of these bats in a cave of Uganda has diversity much greater than that found in humans, in addition to being found in healthy bats. A situation that indicates a balance between the parasite and the host.
Although we worry a lot with these zoonoses (viruses transmitted to humans by animals) and others like the yellow fever, they are generally diseases with recognizable symptoms and with little transmission to humans. Therefore, they tend to cause severe damage locally but do not easily spread globally.
Another factor that must be considered is the vectors. Vectors are the intermediaries that bring the virus from a reservoir to humans. The most frequent are the mosquitoes, transmitters of various diseases like dengue and West Nile Fever. Diseases that depend on vectors are restricted to the locations where the vectors occur, and can be prevented by combating the vector, such as the control campaigns of Aedes aegypti for the prevention of dengue.
What about the Influenza?
In the case of Influenza, various of such factors favors the virus. Their natural reservoirs are aquatic birds, carriers of the virus in their digestive system that have a greater diversity of HA (H1-H16) and NA (N1-N9). These birds are migrants and spread the virus all over the world, especially through lakes where various species are found. With this, the virus is able to circulate worldwide in little time and is always in contact with human beings.
The vectors of the Influenza are also special. They are reared animals, especially pigs and ducks. In addition to living in contact with wild birds, they are not animals that we can eradicate as a method of prevention; this situation is deteriorated by the rearing techniques of the pigs, the mixture of animals from various locations and the cohabitation of a large number of them, which favors the transmission and circulation of Influenza.
Another aggravating factor is the reassortment. Reassortment is the mixture of two or more viruses that infect a same cell and mix their genes on leaving. In addition to the pig having the same type of cell receptor as we, it can be infected by human and bird viruses, serving as an intermediary where the virus can adapt to humans and be transmitted more easily. The ideal host for the virus to reassort and obtain proteins that are new to our immune system.
The mutations also favor the virus. The Influenza has RNA as genetic material and to replicate it, it uses its own RNA polymerase, which is prone to error. With this, on every replication cycle, the virus mutates its genetic material and changes its proteins. It changes enough to cause our antibodies not to recognize the virus any longer after some years, and this way, the population susceptible to it is not reduced and the transmission chain is maintained.
The variation of the virus also contributes to prevent the vaccine from being efficient for a long time. While only one vaccine was enough to combat the smallpox virus, which was distributed worldwide and eradicated the disease in humans, we have to develop new vaccines every year to combat Influenza, and the six months period between the isolation of the circulating virus and the distribution of the vaccine may be enough for it to lose its efficiency due to mutations of the virus.
Lastly, about the transmission of the virus. Although the ducks and pigs may serve as vectors for the bird virus, once adapted to humans they transmit perfectly well. On top of it there is the fact that the flu symptoms are common to various other diseases and about 1/3 of sick persons do not develop the symptoms (although they can transmit the virus) and we have a situation difficult to control.
Sneezes, cough and hands stained with mucus carrying the Influenza are very efficient methods of transmission, and they are worsened by our growing agglomeration in public places, transport vehicles and others. Therefore, the virus is not only transmitted easily but also has a population with increasing susceptibility and intimate cohabitation.
What concerns us after all is this confluence of factors. A large natural reservoir, intermediaries which we cannot eradicate, enough variability to escape our immunity and vaccine at regular intervals, chances of reassorment and introduction of new genes of the virus in the human population and an easy and fast transmission, aggravated by the growing ability of travels and large agglomerations.
Wolfe, N., Dunavan, C., & Diamond, J. (2007). Origins of major human infectious diseases Nature, 447 (7142), 279-283 DOI: 10.1038/nature05775
Carrat, F., Vergu, E., Ferguson, N., Lemaitre, M., Cauchemez, S., Leach, S., & Valleron, A. (2008). Time Lines of Infection and Disease in Human Influenza: A Review of Volunteer Challenge Studies American Journal of Epidemiology, 167 (7), 775-785 DOI: 10.1093/aje/kwm375