RESEARCH INTERESTS:
Molecular Biology of Retroviruses Immunosuppression as the result of infection with HIV-1 is fatal and is associated with the appearance of opportunistic infections and cancers that include EBV-driven lymphomas and HHV-8-driven Kaposi's sarcoma. Successful suppressive therapy of HIV-1infection has been achieved with the introduction of inhibitors directed at the HIV-1 protease. Therapy failure is associated with the development of drug resistance. A major effort is directed at understanding the role of the protease and proteolytic processing in the virus life cycle, and assessing the nature of drug resistance to protease inhibitors. We are especially interested in defining the extent to which drug resistance mutations compromise the fitness of the drug-resistant virus. A second area of research has to do with the role of the HIV-1 Env protein in pathogenesis and its use in vaccine development. Evolution within the env gene can result in a more pathogenic version of HIV-1 that leads to accelerated disease course. These studies have led to a more general consideration of the nature of selective pressure on the viral envelope protein and the mechanisms at work generating diversity in the viral genome as a result of that selective pressure. Finally, in a collaborative effort with Dr. Robert Johnston and Dr. Nancy Davis, we have been involved in the use of an alphavirus vector to deliver HIV-1 sequences in a vaccine strategy. RECENT PUBLICATIONS:
Tang Y, Swanstrom R. Development and characterization of a new single cycle vaccine vector in the simian immunodeficiency virus model system. Virology. 2007 Patel MB, Hoffman NG, Swanstrom R. Subtype-specific conformational differences within the V3 region of subtype B and subtype C human immunodeficiency virus type 1 Env proteins. J Virol. 2008 Jan;82(2):903-16. Epub 2007 Fluet ME, Whitmore AC, Moshkoff DA, Fu K, Tang Y, Collier ML, West A, Moore DT, Swanstrom R, Johnston RE, Davis NL. Effects of rapid antigen degradation and VEE glycoprotein specificity on immune responses induced by a VEE replicon vaccine. Virology. 2008 Jan 5;370(1):22-32. Epub 2007 Harrington PR, Connell MJ, Meeker RB, Johnson PR, Swanstrom R. Dynamics of simian immunodeficiency virus populations in blood and cerebrospinal fluid over the full course of infection. J Infect Dis. 2007 Oct 1;196(7):1058-67. Epub 2007 Low AJ, Dong W, Chan D, Sing T, Swanstrom R, Jensen M, Pillai S, Good B, Harrigan PR. Current V3 genotyping algorithms are inadequate for predicting X4 co-receptor usage in clinical isolates. AIDS. 2007 Sep 12;21(14):F17-24 Haubrich RH, Jiang H, Swanstrom R, Bates M, Katzenstein D, Petch L, Fletcher CV, Fiscus SA, Gulick RM; AIDS Clinical Trials Group Protocol 359 Team. Non-nucleoside phenotypic hypersusceptibility cut-point determination from ACTG 359. HIV Clin Trials. 2007 Mar-Apr;8(2):63-7 Resik S, Lemey P, Ping LH, Kouri V, Joanes J, Pérez J, Vandamme AM, Swanstrom R. Limitations to contact tracing and phylogenetic analysis in establishing HIV type 1 transmission networks in Cuba. AIDS Res Hum Retroviruses. 2007 Mar;23(3):347-56 Harrington PR, Nelson JA, Kitrinos KM, Swanstrom R. Independent evolution of human immunodeficiency virus type 1 env V1/V2 and V4/V5 hypervariable regions during chronic infection. J Virol. 2007 May;81(10):5413-7. Epub 2007 Cecil C, West A, Collier M, Jurgens C, Madden V, Whitmore A, Johnston R, Moore DT, Swanstrom R, Davis NL. Structure and immunogenicity of alternative forms of the simian immunodeficiency virus gag protein expressed using Venezuelan equine encephalitis virus replicon particles. Virology. 2007 Jun 5;362(2):362-73. Epub 2007 Coetzer M, Cilliers T, Ping LH, Swanstrom R, Morris L. Genetic characteristics of the V3 region associated with CXCR4 usage in HIV-1 subtype C isolates. Virology. 2006 Dec 5-20;356(1-2):95-105. Epub 2006 Foulkes JE, Prabu-Jeyabalan M, Cooper D, Henderson GJ, Harris J, Swanstrom R, Schiffer CA. Role of invariant Thr80 in human immunodeficiency virus type 1 protease structure, function, and viral infectivity. J Virol. 2006 Jul;80(14):6906-16 |
Biochemistry and Biophysics - UNC School of Medicine
