My research focuses on arbovirus pathogenesis and cellular interactions during infection in the mosquito and the mammal, examining the host-virus-vector interface. Arboviral diseases are one of the leading causes of morbidity and disability in the developing world. The majority of these diseases lack an effective vaccine or specific treatment to prevent infection and control transmission. We aim to uncover mechanisms at play during the entire arboviral transmission cycle, from infection in the mammal to acquisition in the mosquito vector, and transmission from the mosquito back to the mammal.
Currently our research is focused on dengue and Zika viruses, both flaviviruses transmitted by Aedes mosquitoes. Dengue virus causes serious human disease and mortality worldwide. Infection results in a severe febrile illness, occasionally leading to lethal hemorrhagic fever, especially in children. In recent years, there has been increased epidemic activity and geographic expansion of dengue infection along with its mosquito vector, and it is considered a serious emerging global health problem. The disease has an enormous impact on the health and economies of tropical and subtropical regions, with dengue infections occurring in Asia, the Americas, Africa, Pacific and Mediterranean regions. While most cases in the United States occur in travelers returning from endemic areas, there have been recent outbreaks in Texas, Florida and Hawaii, where transmission occurred on American soil. Zika virus is a rapidly emerging flavivirus that has recently been responsible for severe disease outbreaks in the Western hemisphere. Zika fever is characterized by mild headache, rash, fever, malaise, conjunctivitis, and joint pain. There are no targeted therapeutics or prophylactic drugs, and treatment is generally palliative. Recently described neurological complications of Zika virus infection include babies born with microcephaly and the development of Guillain-Barre syndrome in adults. As climate change continues, the range of Aedes, the mosquito vectors of dengue and Zika viruses, is expected to expand northwards, placing an increased proportion of the US public at risk for disease.
There are no vaccines or specific therapeutic agents approved for dengue or Zika virus infection. The development of a safe and effective vaccine for dengue has been hindered by antibody-dependent enhancement, in which exposure to and development of antibodies against one dengue serotype can lead to severe hemorrhagic fever upon infection with a different serotype. Our lab and others have also shown that dengue antibodies can enhance Zika virus infection. We are currently examining the causes and effects of antibody-dependent enhancement of both viruses using primary human cells. As mentioned, both dengue and Zika are transmitted to humans by mosquito vectors. An attractive complement to traditional vaccine design is to induce an immune response in the vertebrate host (infected or non-infected) that will block virus infection of mosquito transmission vectors. These types of vaccine strategies are termed transmission-blocking vaccines (TBVs). Inhibiting the ability of mosquitoes to acquire a dengue virus infection would eliminate an important step in the infection cycle and represent a novel, highly effective method to disrupt the infected patient to mosquito transmission step and limit the size of arboviral outbreaks. We are currently working on the development of TBVs using Aedes mosquito proteins in our lab. Other projects in the lab include examining the impact of human host blood factors on mosquito arbovirus infection, investigating human-mosquito immune cross-talk, looking at the role of skin cells in initial flavivirus infection and what impact immature virions have on both acquisition in the mosquito vector and transmission to mammalian hosts.