- Wen S.C, Schuster J.E, Gilchuk P, Boyd K.L, Joyce S and Williams J.V. (2015) Lung CD8+ T Cell Impairment Occurs during Human Metapneumovirus Infection despite Virus-Like Particle Induction of Functional CD8+ T Cells. J Virol. 89: 8713-8726. | View Abstract
- Schuster J.E, Cox R.G, Hastings A.K, Boyd K.L, Wadia J, Chen Z, Burton D.R, Williamson R.A. and Williams J.V. (2015) A broadly neutralizing human monoclonal antibody exhibits in vivo efficacy against both human metapneumovirus and respiratory syncytial virus. J Infect Dis. 211: 216-225. | View Abstract
- Hastings A.K, Erickson J.J, Schuster J.E, Boyd K.L, Tollefson S.J, Johnson M, Gilchuk P, Joyce S. and Williams J.V. (2015) Role of type I interferon signaling in human metapneumovirus pathogenesis and control of viral replication. J Virol. 89: 4405-4420. | View Abstract
- Erickson J.J, Rogers M.C, Hastings A.K, Tollefson S.J. and Williams J.V. (2014) Programmed death-1 impairs secondary effector lung CD8(+) T cells during respiratory virus reinfection. J Immunol. 193: 5108-5117. | View Abstract
- Erickson J.J, Gilchuk P, Hastings A.K, Tollefson S.J, Johnson M, Downing M.B, Boyd K.L, Johnson J.E, Kim A.S, Joyce S. and Williams J.V. (2012) Viral acute lower respiratory infections impair CD8+ T cells through PD-1. J Clin Invest. 122: 2967-2982. | View Abstract
- Cox R.G, Livesay S.B, Johnson M, Ohi M.D. and Williams J.V. (2012) The human metapneumovirus fusion protein mediates entry via an interaction with RGD-binding integrins. J Virol. 86: 12148-12160. | View Abstract
- Cseke G, Maginnis M.S, Cox R.G, Tollefson S.J, Podsiad A.B, Wright D.W, Dermody T.S. and Williams J.V. (2009) Integrin alphavbeta1 promotes infection by human metapneumovirus. Proc Natl Acad Sci USA. 106: 1566-1571. | View Abstract
The focus of Dr. Williams’ research is the basic and clinical investigation of respiratory viruses. Respiratory infections are the leading cause of death in children less than five years old worldwide. Moreover, respiratory infections are a major cause of disease and death in immunocompromised patients such as transplant recipients.
Our major area of research is the cell entry, immunity, and pathogenesis of human metapneumovirus (HMPV). HMPV is a recently discovered paramyxovirus that is a leading cause of acute lower respiratory tract illness in infants and children worldwide. HMPV causes severe and fatal disease in high-risk individuals, including premature infants, transplant recipients, older adults, and persons with chronic cardiopulmonary disease. We have a comprehensive program of HMPV research including basic and translational components. We published molecular epidemiology studies establishing the importance of HMPV, in the process isolating dozens of field strains collected over twenty years. We use mouse models to study in vivo pathogenesis and immunity to HMPV. We identified RGD-binding integrins as receptors for HMPV and use a variety of experimental approaches to determine mechanisms of attachment, fusion, and entry.
We discovered that HMPV and other acute respiratory viral infections cause impairment of lung CD8+ T cells via PD-1 signaling, a pathway previously associated with chronic infections and cancer. Our lab has generated candidate vaccines and monoclonal antibodies against HMPV and identified mechanisms by which HMPV subverts the host innate immune response. We also conduct collaborative studies of the epidemiology of HMPV and other respiratory viruses with investigators at US and international sites.
We have active HMPV research projects in several areas:
- Host determinants of human metapneumovirus immunity and pathogenesis
- High-throughput Screening for Inhibitors of Human Metapneumovirus
- Respiratory viral infection and vitamin D in Jordanian infants
- Enhanced Active Surveillance Of Pediatric Infectious Diseases And Vaccines
- Mechanisms by which HMPV and other respiratory viruses lead to impaired pulmonary CD8+ T cells
- Candidate vaccines and therapeutic monoclonal antibodies against HMPV
- High-throughput screening for small molecule inhibitors of HMPV
- HMPV inhibition of type I interferon responses
- Integrin-mediated entry of HMPV
- Human T cell responses to HMPV
The overarching theme of our research on HMPV is to elucidate mechanisms of viral pathogenesis, understand the contribution of host immune responses to pathogenesis, and guide the development of interventions against this important human pathogen.