Lark Coffey, an assistant professor in the Department of Pathology, Microbiology and Immunology, UC Davis School of Veterinary Medicine and a member of the Center for Vectorborne Diseases, will speak on "Zika Virus in Macaques, Mice and Mosquitoes: Contrasting Virulence and Transmissibility in Disparate Hosts."
And her host is medical entomologist and seminar coordinator Geoffrey Attardo, assistant professor in the UC Davis Department of Entomology and Nematology. This is part of the department's series of fall seminars.
Coffey says on her website: "Mosquito-borne viruses like Zika, chikungunya, West Nile, St. Louis encephalitis and dengue virus are expanding to cause more human infections worldwide. Unfortunately, no licensed human vaccines for these viruses are available. Management of disease is therefore restricted to palliative care for infected people and minimizing exposure to mosquitoes. Our research focuses on several central themes with a common goal of reducing the burden of disease caused by arboviruses. These include: understanding viral genetic factors that promote arbovirus outbreaks predicting viral mutations that enhance arbovirus transmissibility by mosquitoes and disease in humans or animals increasing safety of candidate live-attenuated vaccines improving arbovirus surveillance in mosquitoes."
Her abstract of her seminar Nov. 7 is technical. "Fetal microcephaly and death are now recognized as severe forms of congenital Zika syndrome; however, it is still unclear whether recent Zika virus (ZIKV) mutations contribute to this phenotype," Coffey says in her abstract. "We identified a single intrahost variant in the ZIKV NS2B protein (NS2BM1404I) from a rhesus macaque (RM) fetus that died after experimental ZIKV inoculation in the first trimester. Targeted deep sequencing flanking NS2B1404 in subsequent cohorts of RM mothers and their fetuses identified NS2BM1404I at minority frequency and sometimes at consensus levels in 3 additional dead or stillborn RM fetuses and/or the plasma of their mothers and in 2 more RM mother and fetus pairs whose fetuses survived to near term or were born alive. In outbred pregnant mice inoculated subcutaneously, we observed that NS2BI1404 engineered into an infectious clone confers fetal infection while ZIKV-NS2BM1404 does not. By examining sequence data from recent epidemics, we found that NS2BM1404I occurs rarely (5/500, 1%) in consensus human ZIKV genomes.
"We also deep sequenced ZIKV genomes from non-pregnant human adults, infants, and Ae. aegypti from the epidemic and observed that NS2BI1404 was more often present at intra-host levels in humans compared to mosquitoes," she continues in her abstract. "Since the primary ZIKV transmission cycle is human-mosquito-human, viral mutations that arise in one host must be maintained in the alternate host to be perpetuated. We therefore hypothesized that ZIKV NS2BM1404Imay not be efficiently transmitted by Aedes aegypti mosquitoes, explaining its low frequency in humans during outbreaks. Using infectious clone-derived ZIKV, we examined vector competence in Ae. aegypti from Puerto Rico. Although infection and dissemination rates were not different, we found that Ae. aegypti did not transmit ZIKV-NS2BI1404 as efficiently compared to ZIKV-NS2BM1404 5 [7/20 (35%) versus 10/20 (50%), p>0.05] and 7 [3/20 (15%) versus 13/20 (65%), P<0.001, Chi-squared] days post-feed. The poor transmissibility of this potentially vertebrate adaptive ZIKV mutation may explain its low frequency in febrile humans. This data highlights the evolutionary complexity during arbovirus transmission cycles and suggests that some pathogenic viral mutations are not likely to spread in epidemics."
Coffey received her bachelor of science degree in biology from the University of the South, Sewanee, Tenn., in 2000, and her doctorate in experimental pathology at the University of Texas Medical Branch, Galveston, Texas in 2005.
The annual UC Davis Research Symposium on the Designated Emphasis in the Biology of Vector-Borne Diseases (DEBVPD) takes place from 3 to 8 p.m., Thursday, May 3 in the Putah Creek Lodge, and will feature two speakers and a graduate student poster session.
Addressing the gathering will be speakers Lark Coffey, member of the Department of Pathology, Microbiology and Immunology in the UC Davis School of Veterinary Medicine, and research director Stéphane Blanc of the program, Biology and Genetics of Plant-Pathogen Interactions at the Institut National de la Recherche Agronomique (INRA) in Montpellier, France.
The event begins with opening remarks at 3:10, followed by Coffey's presentation at 3:20 on “Contrasting Virulence and Transmissibility in Disparate hosts: A Zika Virus Mutation that Associates with Fetal Death in Rhesus Macaques Reduces Transmission by Aedes aegypti Mosquitoes.”
The graduate student poster session begins at 4:05 p.m., with Laura Backus, Nicholas Booster, Marisa Donnelly, Jessica Franco, Karen Holcomb, William Louie, Risa Pesapane, Benjamin Plourde, Maribel Portilla, Jennifer Reed, Kasen Riemersma, Pascale Stiles and Olivia Winokur presenting.Blanc's address follows at 5:30 p.m. on "Current Research Trends in the Interaction between Plant Viruses and Insect Vectors."
Coffey focuses her research on the ecology and evolution of arthropod-borne viruses, including Zika, West Nile and Chikungunya. They are significant causes of human disease, with no vaccines or treatments beyond palliative care.
Her team seeks to understand patterns of viral molecular evolution in enzootic and epidemic settings and the viral genetic factors that promote emergence of epidemic variants via host range changes. Studies also focus on how intrahost arboviral genetic diversity generated by error-prone viral replication to produce minority variants influences infectivity and transmissibility in mosquito and vertebrate hosts. The team is also developing approaches to improve arbovirus surveillance.
Coffey received her bachelor's degree in biology at the University of the South, Sewanee, Tenn., and her doctorate in experimental pathology from the University of Texas Medical Branch in Galveston, Texas. She then conducted research at the Institut Pastuer in Paris, France, and at the University of San Francisco.
Blanc has been with INRA Montpellier since 1997 and with his current research unit since 2004. He studies interactions among viruses, insect vectors and plant hosts. His group works at multiple scales from molecular to viral genetics and population dynamics. In addition, he has an innovative focus on understanding multipartite viruses.
He received his undergraduate degree in biology of populations and organisms from the University of Montpellier. His doctoral research, also at the University of Montpellier, addressed molecular mechanisms of plant virus transmission by insect vectors. After receiving his doctorate in 1993, he studied plant virus vector-transmission at the University of Kentucky, Lexington, with Professor T. P. Pirone.
The Department of Entomology and Nematology and the Department of Plant Pathology are home to the Designated Emphasis in the Biology of Vector-borne Diseases (DEBVBD).
It's good to see UC Davis mosquito researchers featured in the KQED's science program, "Deep Look."
KQED journalists recently traveled to the UC Davis campus to visit several mosquito labs. The end result: The KQED news article on “How Mosquitoes Use Six Needles to Suck Your Blood,” which includes an embedded video. The National Public Radio's health blog, “Shots,” includes a shorter version. You can also see the Deep Look video on YouTube (embedded below).
- Parasitologist and entomologist Shirley Luckhart, professor in the UC Davis School of Medicine's Department of Medical Microbiology and immunology and the Department of Entomology and Nematology
- Medical entomologist Gregory Lanzaro, professor, Department of Pathology, Microbiology and Immunology (PMI), UC Davis School of Veterinary Medicine, and an associate of the UC Davis Department of Entomology and Nematology
- Chemical ecologist Walter Leal, professor in the UC Davis Department of Molecular and Cellular Biology and former chair of the UC Davis Department of Entomology
- Virologist Lark Coffey of PMI
- UC Davis post-doctoral researcher Young-Moo Choo of the Leal's lab who discovered a receptor by dissecting mosquitoes' mouthparts and genetically testing them.
“Mosquitoes don't find the blood vessel randomly," Leal said, pointing out that the receptors respond to chemicals in the blood.
The receptor that the Leal lab discovered is called 4EP, and may lead to drug companies developing new mosquito repellents. “First they'd need to find a repellent against the receptors," Choo told Quirós. "Then they'd treat people's skin with it. When the mosquito tried to penetrate the skin, it would taste or smell something repulsive and fly away.”
But back to the video. The narrator reveals the sophisticated tools that the mosquito uses to draw your blood.
- A protective sheath retracts: inside are six needles, and two of them have sharp, tiny teeth
- The mosquito uses the sharp, toothed needles to saw through your skin
- Other needles hold the tissues apart while she works
- Receptors on the tip of one of her needles guide her to your blood vessel.
- She uses the same needle like a straw to sip your blood
- She uses another needle to spit chemicals into you so your blood will flow easily. That's what gives you the itchy, scratch-me-now welts.
Of course, it's the viruses or parasites that the mosquito transmits that can sicken and kill us. Depending on the species, they give us such diseases as malaria, dengue, yellow fever, West Nile virus, Zika virus and elephantiasis.
As KQED says "This is the deadliest animal in the world. Mosquitoes kill hundreds of thousands of people each year...the most vulnerable people: children and pregnant women."
KQED performed an excellent public service in reporting and sharing this scientific information, gleaned from the UC Davis labs. The first day the video was posted, it drew nearly 400,000 views.
We worry about what mosquitoes do to us. If mosquitoes could talk--if they could communicate with us--they ought to be worried about what we're going to do to them.
(Access the American Mosquito Control Association website to learn the biology of mosquitoes.)