Research in the Weinberg Laboratory
Research in the Weinberg Laboratory is focused on understanding interactions between adenoviruses and host immune responses. Respiratory infection with a human adenovirus can present with varying severity, ranging from mild upper respiratory tract infections to more severe pneumonia and destructive lung disease. Adenovirus infection of immunocompromised patients, particularly bone marrow transplant (BMT) recipients, can be particularly devastating, often resulting in rapidly disseminated infection and death. Emerging evidence suggests a role for persistent adenovirus infection in chronic lung diseases such as chronic obstructive lung disease (COPD) and asthma. The strict species specificity of the human adenoviruses precludes a complete study of their pathogenesis. Instead, we use a mouse pathogen, mouse adenovirus type 1 (MAV-1), to study the pathogenesis of an adenovirus in its natural host.
Our research seeks to define mechanisms by which host inflammatory responses are induced by viral infection and the contributions that specific components of these host responses make to the control of acute viral infection. Trainees in the laboratory will have the opportunity to participate in a variety of projects related to this work. Prostaglandin E2 (PGE2) is a lipid-derived mediator that influences host immune function in many ways. A central goal of our research program is to characterize ways in which PGE2 modulates the pathogenesis of MAV-1 respiratory infection. Specifically, we use MAV-1 to study the effects of PGE2 on viral replication and virus-induced inflammation in a normal host, in PGE2-deficient and PGE2-unresponsive hosts, and in a BMT model in which PGE2 is aberrantly overexpressed. A second major goal of our research is to characterize the contributions of specific cytokines and immune cells to the clearance of MAV-1 during acute infection. We define ways in which these immune responses to MAV-1 differ between neonates and adults. In related work, we are interested in learning how these different responses in neonates lead to increased susceptibility to infection and to long-term effects on lung physiology, such as increased airway hyperreactivity. We anticipate that information derived from our work will enhance the understanding of the adenovirus pathogenesis. Ultimately, we hope that our work will identify novel virus- and host-specific targets to exploit for the treatment of adenovirus infections and adenovirus-associated lung disease.
Weinberg, JB, Lutzke, ML, Kunkel, SL and Rochford, R. Elevated chemokine responses are maintained in lungs after clearance of viral infection. Journal of Virology 2002; 76(20): 10518-10523. PMCID136555
Weinberg, JB, Lutzke, ML, Alfinito, R and Rochford, R. Mouse strain differences in the chemokine response to acute lung infection with a murine gammaherpesvirus. Viral Immunology 2004; 17(1): 69-77. PMCID not available.
Weinberg, JB, Stempfle, GS, Wilkinson JE, Younger JG and Spindler, KR. Acute respiratory infection with mouse adenovirus type 1. Virology 2005; 340:245-254. PMCID1351061
Weinberg, JB, Jensen, DR, Gralinski, LE, Lake, AR, Stempfle, GS and Spindler, KR. Contributions of E1A to mouse adenovirus type 1 pathogenesis following intranasal inoculation. Virology 2007, 357(1):54-67. PMCID1764815
Nguyen, Y, Anderson, VE, McGuffie, BA and Weinberg, JB. Gammaherpesvirus modulation of mouse adenovirus type 1 pathogenesis. Virology 2008, 380:182-190. PMCID2577692
Anderson, VE, Nguyen, Y and Weinberg, JB. Effect of allergic airways disease on mouse adenovirus type 1 respiratory infection. Virology 2009, 391:25-32. PMCID2759195
Ashley, SL, Ameres, SM, Gerrard, SR, Foreman, O, Eaton, KA, Weinberg, JB, and Spindler, KR. Mouse strain differences in susceptibility to Punta Toro virus. Virus Research 2010; 157:71-75. PMC Journal - In Process
Olivadoti, M, Weinberg, JB, Toth, LA, and Opp, MR. Murine gammaherpesvirus alters sleep and induces fatigue in C57BL/6 mice. Brain Behav Immun 2011; 25:696-705. PMC Journal - In Process
Nguyen, YN, Procario, MC, Ashley, SL, Gendler, SJ, O'Neal, WK, Pickles, RS and Weinberg, JB. Effects of Muc1 deficiency on mouse adenovirus type 1 respiratory infection. Virus Research; in press. PMC Journal - In Process