Kansas State University

No guts, no glory: Biologists receive nearly $2.8 million from NIH to study virus escape from mosquito midgut

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Kansas State University associate professors of biology Rollie Clem and Lorena Passarelli have been bouncing ideas off each other since they met in graduate school.

This strategy has recently paid off and resulted in Clem and Passarelli being awarded a four-year $2.8 million grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, to study how mosquitoes transmit viruses.

The two have maintained independent research programs even though they have been married for 20 years and have been research colleagues even longer. However, they have always used each other as sounding boards for ideas, and these discussions recently revealed that their latest research might be connected.

"Lorena's group was working on the problem of how a virus called baculovirus escapes from the midgut, which is the primary site of baculovirus infection in caterpillars," Clem said. "My group was working on apoptosis, a type of cell death, that occurs during virus infection in mosquitoes, when we realized that both processes use some of the same proteins."

Uncovering that both systems -- the caterpillar and the mosquito -- had similarities in the pathway that a virus uses to move through its host provided the couple with incentive to pool their knowledge.

"At the time we were each planning on submitting our own grant proposal to fund our projects, but then we realized that a joint proposal would be more competitive and innovative," Passarelli said.

With the help of their collaborator Alexander Franz from Colorado State University, the three will study how mosquito-borne viruses, such as dengue and Chikungunya viruses, are able to escape a mosquito's midgut after they are ingested and move to the salivary glands, where they can be transmitted to the mosquito's next host.

"There is not much known about the process of how viruses move from the midgut to the salivary glands," Clem said. "All that is known is that there are some examples where certain viruses can infect a strain of mosquito and can't escape the midgut, so there is a block called a midgut escape barrier. The existence of this barrier implies that midgut escape is not simply a passive process." 

To better understand the midgut escape barrier, the trio will be working with Aedes aegypti mosquitoes, which are known for their involvement in transmitting yellow fever and dengue fever. The eventual aim is that this knowledge can be used to prevent virus transmission by mosquitoes in the wild.

"Viruses that are transmitted by mosquitoes are a huge public health problem in many parts of the world and are becoming more of a problem in the U.S.," Clem said. "If we can figure out how to prevent the virus from escaping the midgut of the mosquito then we can hopefully block the transmission of these viruses. However, at this point we are in the early stages of trying to understand what controls the ability of the virus to escape from the midgut."

Insects have a protective mesh lining the midgut called a basal lamina, which is thought to inhibit viruses from escaping the midgut. However, penetrating the basal lamina are tracheal cells, part of a network of cells that aid in gas exchange throughout the insect's body. The tracheal cells reach into the midgut to provide gas exchange for the midgut cells, Passarelli said.

"If the tracheal cells that penetrate the midgut become infected, they can provide a pathway from the midgut to the rest of the insect," Passarelli said. 

Some of Passarelli's work on caterpillars, published in the Proceedings of the National Academy of Sciences in 2010, showed that baculoviruses are able to induce degradation of the tracheal cell basal lamina, infect the tracheal cell and invade the rest of the caterpillar. This led them to hypothesize that a similar process might be triggered by virus infection in mosquito midguts. Preliminary experiments indicated that this might be the case, Clem said.

Clem and Passarelli believe that their marriage is an advantage to them as scientists, since it provides opportunities to discuss science and learn from each other's expertise. However, they don't always agree, which makes for a more interesting discussion.

"Having different points of view is an advantage for our research," Clem said. "We met as graduate students in the same lab and from the very beginning we have worked well together."

Their partnership does not just end at research and marriage. They also teach a class together, BIOL 730 General Virology, and they are exercise partners. 

"Running together provides a relaxing setting to come up with new research ideas," Passarelli said. "Some of our best discussions happen while we are running."

Both Clem and Passarelli received their doctoral degrees from the University of Georgia and joined Kansas State University's Division of Biology in 1997.