Andrea Gamarik explains molecular mechanisms in dengue
CONICET/DICYT Andrea Gamarnik is a principal researcher at the Conicet. She completed her doctorate in Pharmacy and Biochemistry at the University of Buenos Aires (UBA) in 1993 and the following year she began to study poliomyelitis in the US. In 2001, she decided to come back to Argentina and became part of the Leloir Institute Foundation, where she founded the Molecular Virology Laboratory in which scientists have been studying molecular mechanisms involved in dengue virus for the past 14 years.
In the following interview, the researcher explains how this virus multiplies and infects human and mosquito’s cells.
Why does the dengue virus have to adapt?
Mosquitoes and humans have different immune systems. The dengue virus has to escape from the immune system of men and when it is in a mosquito, it also has to escape from it. Besides, it has endure different temperatures because the human body temperature is 37 centigrade grades and the mosquito’s one is at room temperature. There are several biological questions regarding the way in which the virus multiplies and is efficient in human and mosquitoes cells.
How does it do it?
We found that it has to reprogram its genetic material to adapt to the environments. Viruses are not all equal; they are a population of similar but not identical individuals, and that is what allows them to adapt to different environments quickly and develop, for instance, resistance to antiviral drugs.
How does the dengue adapt to different environments?
A virus infects a cell and multiplies, and from one, thousands of them are formed. However, they are not identical. The small differences have to do with the fact that virus’ mechanism that is in charge of multiplying it makes mistakes in the genetic material. The virus adapts to a speed thousands of times faster than a bacteria or any other organism because the “mistakes” are positive: they provide diversity which provides an advantage to those that have them.
What changes in its genetic material?
Viruses adapt easily and thus they can change the host effortlessly. For instance, major flu outbreaks were caused because from poultry or pigs these viruses “jumped” to humans. There is something that allows the virus to pass from one species to another. So far, all these changes happened in proteins such as in the case of the flu. But in the dengue virus we found that what changes are the signals in the RNA. Those viruses more adapted to multiply in mosquitoes have disadvantages to do it in human cells, because there is an opposite selection process in each host. This is the first example in the literature on a virus that has to change RNA structures to adapt to different hosts. This finding is very interesting because it provides a new way to study how the virus adapts and evolves when it has to jump from one species to another.
How did you achieve those results?
We took virus from infected mosquitoes and conducted deep sequencing, that is to say, we deeply sequenced thousands and thousands of virus we obtained from Aedes aegypti. We found the differences we compared that viral population with the one that can be obtained from human cells.
Could these studies be applied to other viruses transmitted by mosquitoes?
The dengue belongs to the genus Flavivirus in the family Flaviviridae, which includes 70 different types, 50 of which infect humans. Among this number, we find yellow fever, West Nile and zika viruses, among others. They all have the same RNA structure found in dengue, whereby this can be extrapolated to several viruses. The chikungunya virus is not a member of this family but it is transmitted by the same mosquito as dengue. Although it does not have the same structure, it is likely to operate with the same mechanism due to the fact that its structure is very similar. Hence it is likely to extrapolate the studies.
Would it be possible to think about the development of a vaccine from this find?
At our laboratory, we are conducting several projects focused in understanding the virus and in generating knowledge in order to find methods to control infections, either with vaccines or antivirals. In particular, this study provides information regarding dengue transmission. This virus is only transmitted by the Aedes mosquito genus – the rest of the mosquitoes do not transmit it- , so this finding could explain the reason for this. Our major aim is to develop a vaccine but it is rather complicated and so far none of them has been accepted. I believe that eventually we will have an effective vaccine, but it will take time. The society has to raise awareness on mosquito control and at the same time we must provide knowledge to develop vaccines or antivirals.
Why is it necessary to study the dengue virus?
I studied at the UBA, where I also obtained my doctorate and then I went to US. When I came back to Argentina, in 2001, I had to select a field of study and at that time I thought that that was a crucial issue in Latin America. Although the subject was not so present in Argentina, in Brazil and in other countries the dengue was an alarming issue. I thought about choosing about a relevant biological system for the region and at that time there were not many laboratories working on that. For that reason, I opened a laboratory devoted to learn how the virus works. We aim to provide knowledge to find solutions. Furthermore, it is also important to train people who will be able to understand other viruses.
How about the research in terms of the dengue?
We are working in several lines of research. Our following objective is to find why the virus has to change to better infect humans and mosquitoes. So far we have proved how it happens at a molecular level and now we would like to understand the molecular basis of why this happens. This study is never-ending, once something is discovered; it leads you to another one. We are generating knowledge on a virus that currently ravages health systems in all Latin America. Although this subject is not presently alarming in our country, it is necessary to prevent and warn the society so as not to have a more serious problem.