Professor of Biochemistry & Biophysics, UNC-CH
PHD - University of California, Irvine
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-1 infection 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.
- Liu MKP, Hawkins N, Ritchie AJ, Ganusov VV, Whale V, Brackenridge S, Li H, Pavlicek JW, Cai F, Abrahams M-R, Treurnicht F, Hraber P, Riou C, Gray C, Ferrari G, Tanner R, Ping L-H, Anderson JA, Swanstrom R, Cohen M, Abdool Karim SS, Haynes B, Borrow P, Perelson AS, Shaw GM, Hahn BH, Williamson C, Korber BT, Gao F, Self S, McMichael A, Goonetilleke N. Vertical T cell immunodominance and epitope entropy determine HIV-1 escape. J Clin Invest 123:380-393, 2013.
- Liao H-X, Tsao C-Y, Alam M, Muldoon M, Vandergrift N, Ma B-J, Lu X, Sutherland L, Scearce R, Bowman C, Parks R, Chen H, Blinn J, Lapedes A, Watson S, Xia S-M, Foulger A, Hahn B, Shaw G, Swanstrom R, Montefiori D, Gao F, Haynes B, Korbe B. Antigenicity and Immunogenicity of Transmitted/Founder, Consensus and Chronic Envelope Glycoproteins of Human Immunodeficiency Virus Type 1. J Virol 87:4185-4201, 2013.
- Fouda GGA, Mahlokozera T, Salazar-Gonzalez J, Salazar M, Learn G, Kumar SB, Dennison SM, Russell ES, Rizzolo K, Jaeger F, Cai F, Vandergrift N, Gao F, Hahn B, Shaw GM, Ochsenbauer C, Swanstrom R, Meshnick SR, Mwapasa V, Kalilani L, Fiscus S, Montefiori DC, Haynes BF, Kwiek JJ, Alam MS, Permar SR. Postnatally-transmitted HIV-1 Envelope variants have similar neutralization-sensitivity and function to that of nontransmitted breast milk variants. Retrovirology 10:3. 2013
- Ping L-H, Joseph SB, Anderson JA, Abrahams M-R, Salazar-Gonzalez JF, Kincer LP, Treurnicht FK, Arney LA, Ojeda S, Zhang M, Keys J, Chu H, Moore P, Salazar MG, Iyer S, Jabara C, Kirchherr J, Mapanje C, Ngandu N, Seoighe C, Hoffman I, Gao F, Tang Y, Labranche C, Lee B, Saville A, Vermeulen M, Fiscus S, Morris L, Karim SA, Haynes BF, Shaw GM, Korber BT, Hahn BH, Cohen MS, Montefiori D, Williamson C, Swanstrom R. Comparison of the Viral Env Protein From Acute and Chronic Infections of Subtype C HIV-1 Suggests A New Strategy For Immunogen Design. J Virol in press, 2013. PMC in process.
- Potempa M, Swanstrom R. Integrating the HIV-1 assembly/maturation pathway. Proc Natl Acad Sci USA 110:8327-8328, 2013. PMC in process. Pollom E, Dang KK, Potter EL, Gorelick RJ, Burch CL, Weeks KM, Swanstrom R. Comparison of SIV and HIV-1 Genomic RNA Structures Reveals Impact of Sequence Evolution on Conserved and Non-conserved Structural Motifs. PLoS Pathogens 9(4):e1003294. 2013.
- Russell ES, Ojeda S, Fouda GG, Meshnick SR, Montefiori D, Permar SR, and Swanstrom R. HIV-1 subtype C variants transmitted through the bottleneck of breastfeeding are sensitive to new generation broadly-neutralizing antibodies directed against quaternary and CD4-binding site epitopes. AIDS Research and Human Retroviruses in press, 2013.
- Swanstrom R and Coffin JM. HIV-1 Pathogenesis: The Virus. In HIV: From Biology to Prevention and Treatment (Bushman FD, GJ Nabel, and R Swanstrom, Eds). Cold Spring Harbor Perspectives In Medicine. pp 159-176, 2012.
- Coffin JM and Swanstrom R. HIV Pathogenesis: Dynamics and Genetics of Viral Populations and Infected Cells. In HIV: From Biology to Prevention and Treatment (Bushman FD, GJ Nabel, and R Swanstrom, Eds). Cold Spring Harbor Perspectives In Medicine. pp 177-191, 2012.
- Henderson GJ, Lee S-K, Irlbeck DM, Harris J, Kline M, Pollom E, Parkin N, and Swanstrom R. Interplay Between Single Resistance-Associated Mutations in the HIV-1 Protease and Viral Infectivity, Protease Activity, and Inhibitor Sensitivity. Antimicrobial Agents and Chemotherapy 56:623-633, 2012.
- Arrildt KT, Joseph SB, Swanstrom R. The HIV-1 Env protein: a coat of many colors. Current HIV/AIDS Reports 9:52-63, 2012. Valley-Omar Z, Sibeko S, Anderson J, Goodier S, Werner L, Arney L, Naranbhai V, Treurnicht F, Abrahams M-R, Bandawe G, Swanstrom R, Abdool Karim Q, Abdool Karim S, Williamson C. CAPRISA 004 Tenofovir Microbicide Trial: No impact of Tenofovir gel on the HIV transmission bottleneck. J Inf Dis 206:35-40, 2012.
- Lee S-K, Potempa M, Kolli M. Ozen A, Schiffer C, and Swanstrom R. Context surrounding processing sites is crucial in determining cleavage rates of a subset of the processing sites in the HIV-1 Gag and Gag-Pro-Pol precursors by the viral protease. J Biological Chem 287:13,279-13,290, 2012.
- Price RW, and Swanstrom R. Editorial Commentary: Targeting Chronic Central Nervous System HIV Infection. Antiviral Therapy 17:1227-1231, 2012.
- Lee S-K, Potempa M, and Swanstrom R. The Choreography of HIV-1 Proteolytic Processing and Virion Assemby. J Biological Chem 287:40867-40874, 2012.
- Moore PL, Gray ES, Wibmer CK, Bhiman JN, Nonyane M, Sheward DJ, Hermanus T, Bajimaya S, Tumba NL, Abrahams M-R, Lambson BE, Ranchobe N, Ping L-H, Ngandu N, Karim QA, Karim SSA, Swanstrom RI, Seaman MS, Williamson W, Morris L. Evolution of an HIV glycan–dependent broadly neutralizing antibody epitope through immune escape. Nature Med 18:1688-1692, 2012.
- Sturdevant CS, Dow A, Jabara CB, Joseph SB, Schnell G, Takamune N, Mallewa M, Heyderman RS, Van Rie A, and Swanstrom R. Central Nervous System Compartmentalization of HIV-1 Subtype C Variants Early and Late in Infection in Young Children. PLoS Pathogens e1003094.
- 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
22-006 Lineberger Cancer Center
Campus Box 7295
Chapel Hill, NC 27599