The main focus of my laboratory is to develop therapies that can treat and cure patients infected with persistent viruses. We use the LCMV mouse model of acute and persistent viral infection to understand what determines a protective immune response and to consider the immune status of the host in their capacity to respond to opportunistic pathogens. Our goal is to design therapies to treat patients that are persistently infected with viruses such as HCV and HIV and discover adjuvant targets to enhance alternative vaccine designs.
A focus of the lab is on understanding and developing therapies to blunt or reverse morbidity following a virus infection. Cachexia is defined as a loss of weight, muscle atrophy, fatigue, weakness, and loss of appetite in someone not actively trying to lose weight. Cachexia can be a sign of various underlying disorders and is a common feature of cancer, sepsis, AIDS, and congestive heart failure. Cachexia syndromes are diverse but with features suggesting a common pathway. We use our developed lymphocytic choriomeningitis virus (LCMV) model of virus infection to study morbidity. In our studies, we have identified 4 distinct stages of wasting and that CD4 T cell maintain virus induced wasting. One goal of the lab is to identify the CD4 response that is involved in wasting in order to develop targets that can reverse the process.
Another focus in the lab is on understanding immune suppression following infection with chronic LCMV. It has been shown that mice persistently infected with LCMV cl-13 are unable to respond immunologically to secondary infections. We have discovered that these LCMV persistently infected mice are immune competent in their ability to clear a second infection even though they do not mount an antigen specific response to the second virus. The clearance of the secondary infection in these LCMV cl-13 infected mice is dependent on an IFNg induced antiviral state. The IFNγ induced antiviral state is effective regardless of the route of secondary viral entry. Therefore, the in vivo naturally induced antiviral state is dependent on IFNγ rather than type I IFN and persistently infected mice are cable of clearing secondary virus infection non-specifically.
Andrew Stamm, Laura Valentine, Rashaun Willett and Mary Premenko-Lanier. An intermediate dose of LCMV cl-13 caused prolonged morbidity that is maintained by CD4+ T cell+ T cells. 2011. Manuscript in press, Virology. 2012 Apr 10;425(2):122-32. Epub 2012 Feb 4.
Gurfein BT, Stamm AW, Bacchetti P, Dallman MF, Nadkarni NA, Milush JM, Touma C, Palme R, Di Borgo CP, Fromentin G, Lown-Hecht R, Konsman JP, Acree M, Premenko-Lanier M, Darcel N, Hecht FM, Nixon DF. Mol Med. 2012 Feb 29. doi: 10.2119/molmed.2012.00053
Mary Premenko-Lanier, Hodge G, Rota P, Tamin A, Bellini W, McChesney. Maternal antibody inhibits both cellular and humoral immunity in response to measles vaccination at birth. 2006. Virology, Jul 5;350(2):429-32.
Mary Premenko-Lanier, Paul Rota, Gary Rhodes, William Bellini, Michael McChesney A measles DNA vaccine protects infant macaques when administered in the presence of neutralizing antibodies. 2004. J Infect Dis. Jun 1;189(11):2064-2071.
Mary Premenko-Lanier, Paul Rota, Gary Rhodes, William Bellini, Michael McChesney. Prior DNA vaccination does not interfere with the live, attenuated measles vaccine. 2004. Vaccine. Jan 26;22(5-6):762-5.
Mary Premenko-Lanier, Gary Rhodes, William Bellini, Paul Rota, Michael B. McChesney DNA Vaccination of Infants in the Presence of Maternal Antibody: A Measles Model in the Primate. 2003. Virology. Mar 1;307(1):67-75.