Virus-host interactions involved in the pathogenesis of alphaviruses and flaviviruses. Analysis of virus induced structures and cytoskeletal modifications in mammalian host and insect vector using high-resolution live cell imaging and electron microscopy. Viral determinants of neurotropism, encephalitis, transmission and persistence in BSL-3 pathogens.
Alphaviruses and flaviviruses are vector-borne, enveloped, positive-strand RNA viruses from the Togaviridae and Flaviviridae family respectively. Infectious diseases caused by many of these arthropod-borne viruses (arboviruses) remain an international public health concern as there are no vaccines, prophylactic or therapeutic treatments against these human pathogens. Virus-vector interactions and vector-pathogen adaptation to climate variability play important roles in the emergence and transmission of infectious diseases caused by these viruses. Our lab investigates the virus-host and virus-vector interactions that facilitate virus entry, modification of the host system for virus replication, and dissemination. Using BSL-2 and BSL-3 viruses such as West Nile, dengue, Zika, Sindbis, western equine encephalitis and chikungunya, we aim to investigate the molecular pathogenesis and transmission in mouse models and live mosquitoes. Our long-term goals are to understand molecular details of virus life cycle, and design and develop new strategies to perturb them to control and combat these pathogens.
Spatio-temporal dynamics of alphavirus and flavivirus replication and assembly in mosquito and mammalian cells
Our group is building upon our foundational research on live cell imaging of alphavirus replication and assembly. We are going to expand this research area using modified RNA and protein components of Chikungunya, West Nile, dengue and Zika virus. Utilizing molecular virology, live cell imaging, super-resolution microscopy, and electron microscopy techniques, we are aiming to achieve high spatial and temporal resolution of cellular processes in the context of an invading pathogen. Information obtained from these studies will help to understand how spatial and temporal differences of host and viral components affect different disease outcomes in mammalian host and arthropod vector.
Cytoskeletal modification and virus induced structures associated with viral RNA replication
Many positive-strand RNA viruses manipulate the hosts with multi-functional proteins encoded in their relatively small genome. These viruses also evade the immune system by a myriad of techniques and cause diseases such as arthralgia, encephalitis and hemorrhagic fever. We are interested in mapping the host cellular pathways that are impacted by virus replication to elucidate how positive-strand RNA viruses hijack cellular pathways to efficiently complete the virus lifecycle. Specifically, we are interested in understanding how cytoskeleton modification occurs and how that affects virus cell-to-cell transport, and antibody neutralization. The crosstalk between virus replication components and the host factors that restrict virus replication will help to identify new targets for antivirals.
Understanding viral determinants of neurotropism, encephalitis and persistence
We are planning to unravel the molecular processes involved in virus-receptor engagement during entry and host pathways that restrict virus replication. These studies are aimed at establishing the role of alphavirus and flavivirus envelope proteins in determining neurotropism, neurovirulence, cytopathicity, and neuronal persistence. We are using BSL2 and BSL-3 level neurotropic and encephalitic arboviruses including West Nile virus and western equine encephalitis to unravel molecular pathways in infected neuronal cells that lead to cell death, viral clearance or persistence. Additionally, we are interested in modifying neurotropic viruses to be used as tools to probe various host pathway in neurons.