Department of Biochemistry & Biophysics
Retroviruses have provided some of the greatest scientific opportunities and challenges in recent times. As tumor causing-agents, retroviruses provided us with a window to cellular oncogenes. The spread of human retroviruses (HIV and HTLV) represents a serious and expanding medical threat. There are currently several aspects of the retrovirus life cycle and virus/host interaction under study in my laboratory.
A hallmark of HIV-1 is genetic instability. The virus uses this instability to evade the host immune response, and this same capacity for rapid evolution is at play in generating drug resistance and other types of biological variation. We use genetic variability as a starting point to ask questions about virus transmission, compartmentalization within the host, and determinants of pathogenesis. These areas of research are impacting our understanding of HIV neuropathogenesis and informing future vaccine design.
Another focus of our work has been the study of HIV-1 protein processing mediated by the viral protease. We continue to study the processing pathway and the impact of resistance to protease inhibitors. Finally, in a collaborative effort we have started exploring the role of RNA folding in the virus life cycle.
Russell ES, Kwiek JJ, Keys J, Barton K, Mwapasa V, Montefiori DC, Meshnick SR, Swanstrom R (2011). The genetic bottleneck in vertical transmission of subtype C HIV-1 is not driven by selection of especially neutralization-resistant virus from the maternal viral population. J Virol. 85(16):8253-62.
Anderson JA, Ping LH, Dibben O, Jabara CB, Arney L, Kincer L, Tang Y, Hobbs M, Hoffman I, Kazembe P, Jones CD, Borrow P, Fiscus S, Cohen MS, Swanstrom R; Center for HIV/AIDS Vaccine Immunology (2010). HIV-1 Populations in Semen Arise through Multiple Mechanisms. PLoS Pathog. 6(8):e1001053.
Ince WL, Zhang L, Jiang Q, Arrildt K, Su L, Swanstrom R (2010). Evolution of the HIV-1 env gene in the Rag2-/- gammaC-/- humanized mouse model. J Virol. 84(6):2740-52.
Swanstrom R (2009). Comments from a former Journal of Virology editor. J Virol. 83(21):11412.
Lee SK, Harris J, Swanstrom R (2009). A strongly transdominant mutation in the human immunodeficiency virus type 1 gag gene defines an Achilles heel in the virus life cycle. J Virol. 83(17):8536-43.
Harrington PR, Schnell G, Letendre SL, Ritola K, Robertson K, Hall C, Burch CL, Jabara CB, Moore DT, Ellis RJ, Price RW, Swanstrom R (2009). Cross-sectional characterization of HIV-1 env compartmentalization in cerebrospinal fluid over the full disease course. AIDS. 23(8):907-15.
Schnell G, Spudich S, Harrington P, Price RW, Swanstrom R (2009). Compartmentalized human immunodeficiency virus type 1 originates from long-lived cells in some subjects with HIV-1-associated dementia. PLoS Pathog. 5(4):e1000395.
Ince WL, Harrington PR, Schnell GL, Patel-Chhabra M, Burch CL, Menezes P, Price RW, Eron JJ Jr, Swanstrom RI (2009). Major coexisting human immunodeficiency virus type 1 env gene subpopulations in the peripheral blood are produced by cells with similar turnover rates and show little evidence of genetic compartmentalization. J Virol. 83(9):4068-80.
Schnell G, Ince WL, Swanstrom R (2008). Identification and recovery of minor HIV-1 variants using the heteroduplex tracking assay and biotinylated probes. Nucleic Acids Res. 36(22):e146.
Kwiek JJ, Russell ES, Dang KK, Burch CL, Mwapasa V, Meshnick SR, Swanstrom R (2008). The molecular epidemiology of HIV-1 envelope diversity during HIV-1 subtype C vertical transmission in Malawian mother-infant pairs. AIDS. 22(7):863-71.
Patel MB, Hoffman NG, Swanstrom R (2008). Subtype-specific conformational differences within the V3 region of subtype B and subtype C human immunodeficiency virus type 1 Env proteins. J Virol. 82(2):903-16. Epub 2007 Nov 14.
Harrington PR, Connell MJ, Meeker RB, Johnson PR, Swanstrom R (2007). Dynamics of simian immunodeficiency virus populations in blood and cerebrospinal fluid over the full course of infection. J Infect Dis. 196(7):1058-67. Epub 2007 Aug 29.
Resik S, Lemey P, Ping LH, Kouri V, Joanes J, Pérez J, Vandamme AM, Swanstrom R (2007). Limitations to contact tracing and phylogenetic analysis in establishing HIV type 1 transmission networks in Cuba. AIDS Res Hum Retroviruses. 23(3):347-56.
Harrington PR, Nelson JA, Kitrinos KM, Swanstrom R (2007). Independent evolution of human immunodeficiency virus type 1 env V1/V2 and V4/V5 hypervariable regions during chronic infection. J Virol. 81(10):5413-7. Epub 2007 Feb 28.
Pettit SC, Lindquist JN, Kaplan AH, Swanstrom R (2005). Processing sites in the human immunodeficiency virus type 1 (HIV-1) Gag-Pro-Pol precursor are cleaved by the viral protease at different rates. Retrovirology. 2:66.
Ritola K, Robertson K, Fiscus SA, Hall C, Swanstrom R (2005). Increased human immunodeficiency virus type 1 (HIV-1) env compartmentalization in the presence of HIV-1-associated dementia. J Virol. 79(16):10830-4.
Resch W, Parkin N, Watkins T, Harris J, Swanstrom R (2005). Evolution of human immunodeficiency virus type 1 protease genotypes and phenotypes in vivo under selective pressure of the protease inhibitor ritonavir. J Virol. 79(16):10638-49.
Kitrinos KM, Nelson JA, Resch W, Swanstrom R (2005). Effect of a protease inhibitor-induced genetic bottleneck on human immunodeficiency virus type 1 env gene populations.J Virol. 79(16):10627-37.
Harrington PR, Haas DW, Ritola K, Swanstrom R (2005). Compartmentalized human immunodeficiency virus type 1 present in cerebrospinal fluid is produced by short-lived cells. J Virol. 79(13):7959-66.
Department of Microbiology & Immunology
Center for AIDS Research (CFAR)
Center for HIV/STDs and Infectious Disease (CFID)
Lineberger Comprehensive Cancer Center (LCCC)
Program in Molecular Biology and Biotechnology
Genetics and Molecular Biology
Interdisciplinary Program in Biomedical Sciences