Studies of HIV Pathogenesis and Replication

M.D., University of Rochester, 1966.

HIV, the causative virus of AIDS induces both suppression of the immune system and abnormal activation of it. Much of the former is corrected with potent anti-retroviral therapy, however abnormal activation, manifested by hypergammaglobulinemia, an increased Th-2 and decreased Th-1 response to stimuli persists for many years after otherwise successful therapy. We are characterizing the nature of the abnormal immune activation using blood cells and lymph tissue from patients on long- term therapy for HIV. The goal of these studies is to understand the mechanism for the abnormal immune activation so that corrective measures can be made.
We are also studying specific aspects of HIV entry into mononuclear cells relating to conformational changes that might be induced by host cell proteases. These effects can enhance the binding of portions of HIV env proteins to chemokine receptors on the cell.

Selected Publications

• Tussey LG. Nair US.Bachinsky M. Edwards BH. Bakari J. Grimm K. Joyce J. Vessey R. Steigbigel R Robertson MN Shiver JW. Gepfert PA. Antigen burden is major determinant of human immunodeficiency virus-specific CD 8 T cell maturation state potential: implications for therapeutic immunization. J Infect Dis 187:364-374.,2003
  
  
• Moss RB, Wallace MR, Steigbigel RT, Morrison SA, Giermakowska WK, Nardo CJ, Diveley JP, Carlo DJ: Predictors of HIV-specific lymphocyte proliferative immune responses induced by therapeutic vaccination. Clin Exp Immunol. 128:359-364, 2002.
  
  
• Hirsch MS, Steigbigel R, Staszewski S, Mellors J, Scerpella E, Hirschel B, Lange J, Squires K, Rawlins S, Meibohm A and Leavitt R for the Protocol 039 Study Group: A randomized, controlled trial of indinavir, zidovudine, and lamivudine in adults with advanced Human Immunodeficiency Virus type 1 infection and prior antiretroviral therapy. J Infect Dis 180:659-665, 1999.
  
  
• Morrison SA, Pearson SL, Steigbigel RT: Anti-F(ab')2 antibody in HIV-1 infected individuals. Relationship to hypergammaglobulinemia and to levels of antibody to the V3 loop region of glycoprotein 120. AIDS Research and Human Retroviruses 14(6):491-498, 1998.
  
  
• Handley MA, Steigbigel RT, Morrison SA: A role for urokinase-type plasminogen activator in the human immunodeficiency virus type 1 infection of macrophages. J Virology 70:4451-4456, 1996.