Tonya Colpitts, Ph.D.
Adjunct Assistant Professor of Microbiology
Associate Director of Virology, Moderna, Inc.
B.A. University of Hawaii and Manoa, Honolulu, HI
Ph.D. University of Texas Medical Branch, Galveston, TX
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.
- Londono-Renteria B, Troupin A, Cardenas JC, Hall A, Perez OG, Cardenas L, Hartstone-Rose A, Halstead SB, Colpitts TM. 2017. A relevant in vitro model for the study of Zika virus antibody-dependent enhancement. J Gen Virol 98(7):1702-1712. PMID: 28691657
- Troupin A, Shirley D, Londono-Renteria B, Watson AM, McHale C, Hall A, Hartstone-Rose A, Klimstra WB, Gomez G, Colpitts TM. 2016. A role for human skin mast cells in dengue virus infection and systemic spread. J Immunol 197(11):4382-4391. PMID: 27799312
- Londono-Renteria B, Cardenas JC, Troupin A, Colpitts TM. 2016. Natural Mosquito-Pathogen Hybrid IgG4 Antibodies in Vector Borne Diseases: A Hypothesis. Front Immunol 7:380. PMID: 27746778
- Conway MJ, Londono-Renteria B, Troupin A, Watson AM, Klimstra WB, Fikrig E, Colpitts TM. 2016. Aedes aegypti D7 saliva protein inhibits dengue virus infection. PLoS Negl Trop Dis Sep 15;10(9):e0004941. PMID: 27632170
- Troupin A, Londono-Renteria B, Conway MJ, Cloherty E, Jameson S, Vanlandingham D, Higgs S, Fikrig E, Colpitts TM. 2016. A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection. Biochim Biophys Acta 1860(9):1898-1909. PMID: 27241849
- Londono-Renteria B, Grippin C, Troupin A, Cardenas JC, Colpitts TM. 2016. Human C5a protein participates in the mosquito immune response against dengue virus. J Med Entomol 53(3):505-512. PMID: 26843451
- Londono-Renteria B, Troupin A, Conway MJ, Vesely D, Ledizet M, Roundy CM, Cloherty E, Jameson S, Vanlandingham D, Higgs S, Fikrig E, Colpitts TM. 2015. Dengue virus infection of Aedes aegypti requires a putative cysteine rich venom protein. PLoS Pathog 11(10)e1005202. PMID: 26491875
- Londono-Renteria B, Drame PM, Weitzel T, Rosas R, Gripping C, Cardenas JC, Alvares M, Wesson DM, Poinsignon A, Remoue F, Colpitts TM. 2015. An. gambiae gSG6-P1 evaluation as a proxy for human-vector contact in the Americas: a pilot study. Parasit Vectors 8(1):533. PMID: 26464073
- Conway MJ, Watson AM, Colpitts TM, Dragovic SM, Li Z, Wang P, Feitosa F, Shepherd DT, Ryman KD, Klimstra WB, Anderson JF, Fikrig E. 2014. Mosquito saliva serine protease enhances dissemination of dengue virus into the mammalian host. J Virol. 88(1):164-175. PMID: 24131723
- Voorham JM, Rodenhuis-Zybert IA, Nunez NVA, Colpitts TM, van der Ende-Metselaar H, Fikrig E, Diamond MS, Wilschut J, Smit JM. 2012. Antibodies against the envelope glycoprotein promote infectivity of immature dengue virus serotype 2. PLoS One 7(3):e29957. PMID: 22431958
- Colpitts TM, Barthel S, Wang P, Fikrig E. 2011. Dengue virus capsid protein binds core histones and inhibits nucleosome formation in human liver cells. PLoS One 6(9):e24365. PMID: 21909430
- Colpitts TM, Cox J, Vanlandingham DL, Feitosa FM, Cheng G, Kurscheid S, Wang P, Krishnan MN, Higgs S, Fikrig E. 2011. Alterations in the Aedes aegypti transcriptome during infection with West Nile, dengue and yellow fever viruses. PLoS Pathog 7(9):e1002189. PMID: 21909258
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