Faculty / Research
Sidonie A. Morrison, PhDAssociate Professor of Medicine
Ph. D., Biochemistry, Oxford University, 1973
Our research concerns mechanisms of AIDS pathogenesis, including how host factors normally involved in the inflammatory response modulate infection of cells by HIV-1. For instance, infected macrophages express a proteinase, urokinase type plasminogen activator or uPA, that may be responsible for damage to lung, skin or brain when they take up residence in these tissues. In macrophages, expression of the proteinase is transcriptionally regulated in concert with HIV replication itself. We have found that macrophages in tissue culture secrete uPA in response to contact with HIV virions. The proteinase then binds to HIV-1 and increases its ability to replicate suggesting, essentially, that HIV-1 helps its own entry into target cells. These effects are under investigation using methods that detect transcriptional activation in the form of new DNA-binding proteins and increased expression of specific messenger RNA.
In the HIV-1 infected person, untreated infection is characterized by gradual loss of cellular and humoral immunity despite increased expression of antibodies which are futile, i.e. not to the virus or ineffective against it. We have shown that, in people receiving the most potent antiretroviral drugs for long periods, immune activation is eventually suppressed, though extremely slowly and literally years after detectable HIV has disappeared from the blood. Apparently, therefore, undetectable HIV (e.g. hidden in the lymph nodes or other sites) continues to activate the immune system or, perhaps, new naive lymphocytes stimulate old ones to continue making antibody. Immunocytochemical methods such as flow cytometry, ELISA, ELISPOT and magnetic cell separation assist in distinguishing between these possibilities by demonstrating the presence of markers of activation in the T lymphocyte and B lymphocyte populations from both blood and lymph node.
- Handley MA, Steigbigel RT, Morrison SA (1996) A role for urokinase-type plasminogen activator in human immunodeficiency virus type 1 infection of macrophages. J Virol 70, 4451-4456.
- Moorjani H, Craddock BP, Morrison SA, Steigbigel RT (1996) Impairment of phagosome-lysosome fusion in HIV-infected macrophages. J AIDS & Human Retrovirol 13, 18-22.
- Morrison SA, Pearson SL, Steigbigel RT (1998). Anti-F(ab')2 antibody in HIV type 1 infection: Relationship to hypergammaglobulinemia and to antibody specific to the V3 loop region of glycoprotein 120. AIDS Res & Human Retroviruses 14, 491-498.
- Moss R B; Wallace M R; Steigbigel R T; Morrison S A; Giermakowska W K; Nardo C J; Diveley J P; Carlo D J. Predictors of HIV-specific lymphocyte proliferative immune responses induced by therapeutic vaccination. Clinical & Experimental Immunology. 128(2). May, 2002. 359-364.