Carried by rodents, shrews, moles, voles and bats, hantaviruses are emerging zoonotic viruses that cause hantavirus pulmonary syndrome (HPS) in the New World and hemorrhagic fever with renal syndrome (HFRS) in the Old World. Enhanced overlap of human populations with hantavirus reservoir habitats due to climate and ecological changes is predicted to increase hantavirus incidence in future. Hantaviruses are high-containment agents, thus requiring biosafety level-3 or 4 (BSL-3/4) laboratories for their studies. By transplanting hantavirus surface Gn/Gc glycoproteins into the vesicular stomatitis virus (VSV) genome, we have developed recombinant (rVSV)-based “sheep in wolf’s clothing” pseudotype systems to study hantavirus entry in a BSL-2 setting. Using genetic screens and selections in human haploid cells, we have uncovered host factors, including cholesterol and protocadherin-1 (PCDH1), required for hantavirus entry. Recently, we reported the human asthma-associated gene PCDH1 as a critical host determinant for Andes (ANDV) and Sin Nombre virus (SNV) entry in vitro, and ANDV-induced lethal HPS in vivo. Currently, I am interested in further understanding the mechanism by which PCDH1 facilitates New World hantavirus entry and in exploiting this knowledge to develop anti-hantaviral interventions.
While rodent-borne hantaviruses are mainly responsible for human disease, non-rodent hantaviruses can also cause human infections. My long-term interest is to define the molecular determinants of susceptibility and permissivity in reservoir hosts and humans for pathogenic and non-pathogenic hantaviruses to better understand virus-host co-evolution.
I have also utilized the rVSV system to study entry of the newly discovered filoviruses, Lloviu and Bombali viruses, and helped develop a human monoclonal antibody (mAb)-based pan-ebolavirus therapy.
Given my experience with a diverse array of viruses, I am well-positioned to expand the rVSV platform to other emerging and reemerging viruses of human and veterinary importance to develop antiviral vaccines and mAb-based interventions.