Chikungunya virus is an emerging mosquito-borne alphavirus that causes febrile illness and arthritic disease and is endemic in 110 countries. In November 2023, the US Food and Drug Administration licensed IXCHIQ®, the first chikungunya virus vaccine. A new project we began in July 2025 aims to define alphavirus circulation dynamics in the novel landscape provided by IXCHIQ rollout. This will be accomplished by defining IXCHIQ-mediated protection against disease caused by other human pathogenic alphaviruses, evaluating potential for mosquito-borne IXCHIQ transmission, and determining the impact of prior alphavirus exposure on IXCHIQ efficacy against chikungunya virus infection. These studies involve use of our new non-human primate model of Mayaro virus infection. This project will identify consequences of IXCHIQ rollout in contexts where the vaccine is administered to people with or without prior alphavirus exposure and define the potential for mosquito-borne IXCHIQ spread in areas with Aedes vectors.
St. Louis encephalitis virus (SLEV) re-emergence
St. Louis encephalitis virus (SLEV) is a mosquito-borne flaviviral pathogen that causes febrile illness and sometimes fatal encephalitis that reemerged and spread in the Western US from 2015-2025. In a project funded in 2022 by the National Institutes of Health NIAID, we are assessing the extent by which SLEV reemergence is promoted by augmented infectivity and transmissibility compared to historical strains in avian and mosquito cells and Culex mosquito vectors. A second project that we started in July 2025 also involves comparing the relative fitness of multiple strains of SLEV isolated over time after competition in the same vector and avian hosts. This project also seeks to define infection and transmission dynamics of reemerging SLEV in avian hosts and the role of antibody from prior SLEV or related West Nile virus infection in protection from viremia in avian hosts. This project is significant in that it will define SLEV transmission dynamics in the context of sequential invasion and concurrent spread of 2 Culex-borne human pathogenic flaviviruses endemic to the United States. Information learned from these studies can inform strategies to reduce SLEV disease in people.
In another NIAID funded project, we are developing immunocompetent mouse models of SLEV using recombinant collaborative cross mice to recapitulate the spectrum of human disease outcomes (ranging from febrile illness to encephalitis) and to understand virus kinetics, tropism, pathology, and innate immune responses that associate with protection from neurologic disease. The outcome of this project will the development of new human-relevant mouse models of SLEV which can be further used to study the spectrum of pathogenesis, define virus-host interactions and host genetic determinants of susceptibility and severity, test interventions like therapeutics and candidate vaccines, and rapidly adapt to model human disease for other new or re-emerging encephalitic flaviviruses.
We are developing new human-relevant mouse models of St. Louis encephalitis virus which can be further used to study the spectrum of pathogenesis, define virus-host interactions and host genetic determinants of susceptibility and severity, test interventions like therapeutics and candidate vaccines, and rapidly adapt to model human disease for other new or re-emerging encephalitic flaviviruses.
Together with partners in the One Health Institute, we were part of the NIH funded Centers for Research in Emerging Infectious Diseases (CREID) network. Our EpiCenter for Emerging Infectious Disease Intelligence (EEIDI) was focused on advancing understanding of viral emergence from wildlife in urbanizing environments in Peru and Uganda.
Infectious disease epidemiology
With the Epicenter for Disease Dynamics we are studying the impacts of environmental change on the epidemiology, ecology, and evolution of zoonotic diseases in Southeast Asia via an Ecology and Evolution of Infectious Diseases project funded by the National Science Foundation.
Intrahost genetic diversity and arboviral disease
We are studying how genetically diverse viral populations of chikungunya virus generated by error-prone viral replication influence mosquito-borne virus transmission and disease.
Alphavirus mutation rates
We are performing studies to measure the mutation rate of three alphaviruses using a novel PCR-independent assay that captures lethal mutations. We will use mutation rate measurements to understand alphavirus molecular evolution by defining constancy of and environmental factors that affect it, which can inform the potential for viral escape from countermeasures like drug treatment.
As part of a NIH NIAID Centers for Excellence in Influenza Research and Surveillance (CEIRS) project, we perform surveillance for influenza virus in birds and marine mammals in California.
Together with the California National Primate Research Center including Koen Van Rompay, we generated a pregnant macaque model of human Zika virus disease. In addition to using the model to understand human ZIKV infection dynamics and disease with potential effects on fetal development and transfusion transmission, we are testing candidate vaccines and therapies.
Together with Vitalant Research Institute (formerly Blood Systems Research Institute)/University of California San Francisco, we characterized blood transfusion-transmission of Zika virus in macaques to establish minimal requirements for Zika virus blood or organ transfusion-transmission and to characterize pathogen reduction approaches to interrupt transfusion or organ transmission.
We sequenced Zika virus evolved intrahost in pregnant rhesus macaques to determine whether mutations developed in pregnancy are responsible for fetal neurologic disease and death. Defining the viral determinants of clinical Zika virus outcome in macaques could be translated to candidate vaccines or therapies to protect mothers and their infants against the most severe forms of Zika virus disease. We identified a mutation evolved in pregnant macaques that shows increased viral fitness in pregnant mice, but is more poorly transmitted by Aedes aegypti vectors. These data show that intrahost ZIKV mutations capable of augmenting fitness in pregnant vertebrates may not necessarily spread efficiently via mosquitoes during epidemics.
