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Of molecules and mosquitoes: molecular biology techniques underlie our efforts to sustainably eradicate mosquito-borne viruses

Written by Stephanie Moon, SoGES 2013-2014 Sustainability Leadership Fellow, and PhD Candidate in the Department of Microbiology, Immunology, and Pathology

Not so very long ago, the prevailing belief was that mosquitoes were not capable of transmitting such devastating agents of disease as malaria, Yellow fever virus (YFV) and West Nile virus (WNV). It was believed that YFV was transmitted through mysterious fogs or general filth, and it wasn’t until early in the twentieth century that scientific investigation by the U.S. Army in Cuba uncovered the role of mosquitoes in virus transmission (1). Despite the prevailing public sentiment that it was ridiculous to consider that mosquitoes carried human pathogens, experiments by the U.S. Army led by Dr. Walter Reed in Cuba in the early 1900’s revealed that humans can transmit YFV to mosquitoes and mosquitoes can in turn consistently pass the virus back to humans. Shockingly, these experiments would not have been possible without the help of human volunteers willing to be infected with YFV, and some died as a result of their participation (1). However, the eventual eradication of YFV from Central and North America during the twentieth century would not have taken place without these key experiments defining the transmission cycle and a rigorous multi-pronged approach that aimed to destroy mosquito populations, discover a vaccine, and prevent mosquito-human contact through quarantine efforts, screens and mosquito nets (1).

Laboratory-based research efforts were successful in eradicating YFV from the U.S., but surveillance efforts to detect YFV or research into finding a cure for the disease are still important goals. Aside from contributing to sickness and death in sub-Saharan Africa and Central and South America, there is still a risk of YFV and other mosquito-borne viruses once again gaining a foothold in the U.S. It was also recently reported that the main vector for YFV and the related Dengue virus, Aedes aegypti, has been found in California, and 22 patients have been identified so far as having acquired Dengue virus in Key West, Florida (2).

Today in the U.S., West Nile virus is rapidly becoming a major concern as human and animal cases have burgeoned since the virus was introduced in New York in 1999. Yellow fever virus and its mosquito vector Aedes aegypti were also imported to the New World (thought to derive from West Africa and spread to the Americas as a consequence of the African slave trade) and we know now that the way we changed the landscape during the European expansion into the Americas contributed to the expanding region in which YFV was found (1). For example, razing the forest to create sugar cane plantations in the islands of the Caribbean in the early seventeenth century promoted the formation of new favorable habitats for Aedes aegypti, facilitating the spread of YFV (1). Similarly, the incidence of WNV in the northeastern U.S. has been shown to be higher in urban areas, and our agricultural practices have also contributed to WNV disease incidence in the western U.S. (3, 4).

Because West Nile virus normally exists in a transmission cycle between birds and mosquitoes (with humans and horses acquiring WNV incidentally), the ecology of this virus-host-vector system is in some ways more complex than that of YFV, which is maintained in humans and tree-dwelling monkeys (in the Americas). Eradicating WNV therefore presents a particularly complex challenge, especially as WNV, unlike YFV, has no vaccine. It follows that mitigation efforts will focus on mosquito control rather than disease prevention, which can negatively affect ecosystems by harming other insects and the animals that depend on insects as a food source (5). Coming up with new ways to treat patients infected with WNV and other mosquito-borne pathogens or prevent infection in the first place through vaccinations will permit a more sustainable approach to eradicating these diseases. Therefore, molecular biology research into the underlying molecular mechanisms of virus infection and transmission will be essential for our future efforts if we want a more environmentally friendly, sustainable solution to the problem of mosquito-transmitted viruses.

How do we manage the risk of WNV transmission locally? The city of Fort Collins provides a wealth of information to the public about this process. Data you can access online includes how many patients have been diagnosed with WNV, the severity of their disease symptoms, and fatalities in Larimer County. You can also easily find how many mosquitoes were trapped in certain areas in Larimer County and whether or not they tested positive for WNV online (6). These data are used to determine what actions the city should take to prevent a WNV outbreak. Part of the city’s response to a predicted outbreak is the use of insecticides that kill larval or adult mosquitoes, but they are applied in small areas and only used when the risk of WNV transmission is high. Despite the efforts of the city of Fort Collins to make data and information available to the public about WNV transmission risk and insecticide application, there is controversy surrounding the use of insecticides. A fairly recent article in the Coloradoan (http://noconow.co/1hqQcti) discusses some the pitfalls of the current system the city uses to decide when and where to spray insecticides (7). One major problem with our current system is the way that we decide when to spray (7). Because the city won’t spray insecticides until several human cases are reported, there is a delay of almost a month between when people are getting infected with WNV and when they come down with symptoms and therefore when the city may take action (7). We could potentially stop this delay by relying more on mosquito surveillance efforts (7) and by developing improved diagnostics that will detect infection in people who are at risk of infection before the onset of symptoms.

The way that we currently evaluate and abrogate the risk of WNV transmission locally is rooted in molecular biology techniques, as both surveillance and (some) diagnostic tests rely on a method called the polymerase chain reaction (PCR) to detect viral genetic material. Unfortunately, our current repertoire of diagnostic tests are not useful until the patient has symptoms of the disease, so there is a need for more rapid, reliable diagnostic tests to detect WNV before the onset of illness. Surprisingly, there are no specific treatments or human vaccines for many important mosquito-borne viral diseases, including WNV. Research aimed at developing new vaccines, diagnostic tests and exposing new viral (or host) drug targets to mitigate the onset of disease symptoms will be a crucial component of a sustainable strategy for disease control. Laboratory-based research efforts can potentially also pinpoint why certain viruses cause disease or spread across the globe.

My research is focused on how a large group of arthropod-borne viruses including Dengue virus and WNV cause disease at the cellular and molecular level. If we can determine what factors are required for viruses to replicate in human cells, then we can potentially develop novel treatments to reduce the symptoms of the disease. Furthermore, by studying the common mechanisms that many different viruses use to cause disease, we could ultimately derive a common treatment. Many viruses that aren’t transmitted by mosquitoes (including Hepatitis C virus and Bovine viral diarrhea virus- a common ailment of cattle) are close relatives of YFV, Dengue virus, and WNV. Our work has uncovered some exciting mechanisms that these related viruses share to potentially cause disease in humans and animals that you can read about here: http://bit.ly/1lF4M0x (8). Ultimately, research efforts should contribute to the production of treatments, vaccines, and sustainable methods of implementing both to supplement or replace our current approaches that rely heavily on mosquito control to mitigate disease risk in humans and animals.

Works cited and suggested reading:

(1) McNeill, JR. Mosquito Empires: Ecology and War in the greater Caribbean, 1620-1914. New York: Cambridge University Press, 2010. Press.

(2) Centers for Disease Control and Prevention- Dengue Homepage. http://www.cdc.gov/dengue/epidemiology/local_dengue.html. 27 Sept. 2012. Accessed 8 Jan 2014.

(3) Brown HE, Childs JE, Diuk-Wasser MA, Fish D. Ecologic factors associated with West Nile virus transmission, northeastern USA. Emerg Infect Dis [serial on the Internet]. 2008 Oct [8 Jan. 2014]. Available from http://wwwnc.cdc.gov/eid/article/14/10/07-1396.htm

(4) Kilpatrick AM. “Globalization, land use, and the invasion of West Nile virus” Science. 2011 Oct 21; 334(6054):323-7. doi: 10.1126/science.1201010.

(5) U.S. Fish & Wildlife Services, Appendix K4, Environmental Effects of Mosquito Control www.fws.gov/cno/refuges/DonEdwards/CCP-PDFs/Appendix-K4_EffectsofMosquitoControl.pdf 2004. Accessed 1 Jan. 2014.

(6) Colorado Mosquito Control, Inc. http://www.comosquitocontrol.com/larimer.html 2010. Accessed 8 Jan. 2014.

(7) Duggan, Kevin. “Fort Collins’ West Nile spraying could fly in new directions” Coloradoan.com. The Coloradoan, 12 Nov. 2013. http://www.coloradoan.com/apps/pbcs.dll/article?AID=2013311090084 Web. 6 Jan. 2013.        

(8) Moon, SL and Wilusz, J. Rage against the (cellular RNA decay) machine. PloS Pathog. 2013 Dec 9 (12):e1003762. doi: 10.1371/journal.ppat.1003762.

 

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