DF/HCC Program Affiliation

Cancer Immunology

Research Abstract

Our laboratory studies the mechanisms of herpes simplex virus productive infection of epithelial cells and latent infection of neuronal cells and the host immune response to HSV infection. Studies of productive infection involve the mechanisms of regulation of viral gene expression and intranuclear localization of viral regulatory and DNA replication proteins. Our work on latent infection has identified novel gene regulatory pathways in neurons that lead to nonpermissive infection. Our studies of the host immune responses to HSV have led to the development of genetically engineered replication-defective mutant HSV-2 strains as candidate vaccines for genital herpes and as vectors for AIDS vaccines. We are also using HSV vectors to express prostate cancer antigens as potential cancer vaccines, and we are participating in the study and design of HSV strains that specifically kill tumor cells.

Publications

• Garber DA, Schaffer PA, Knipe DM.A LAT-associated function reduces productive-cycle gene expression during acute infection of murine sensory neurons with herpes simplex virus type 1.J Virol 1997 Aug;71(8):5885-93.
  9223478
• Uprichard SL, Knipe DM.Assembly of herpes simplex virus replication proteins at two distinct intranuclear sites.Virology 1997 Mar 3;229(1):113-25.
  9123852
• Dodson AW, Taylor TJ, Knipe DM, Coen DM.Inhibitors of the sodium potassium ATPase that impair herpes simplex virus replication identified via a chemical screening approach.Virology 2007 Sep 30;366(2):340-8.
  17544048
• Petit CM, Chouljenko VN, Iyer A, Colgrove R, Farzan M, Knipe DM, Kousoulas KG.Palmitoylation of the cysteine-rich endodomain of the SARS-coronavirus spike glycoprotein is important for spike-mediated cell fusion.Virology 2007 Apr 10;360(2):264-74.
  17134730
• Melroe GT, Silva L, Schaffer PA, Knipe DM.Recruitment of activated IRF-3 and CBP/p300 to herpes simplex virus ICP0 nuclear foci: Potential role in blocking IFN-beta induction.Virology 2007 Apr 10;360(2):305-21.
  17126870
• Watanabe D, Brockman MA, Ndung'u T, Mathews L, Lucas WT, Murphy CG, Felber BK, Pavlakis GN, Deluca NA, Knipe DM.Properties of a herpes simplex virus multiple immediate-early gene-deleted recombinant as a vaccine vector.Virology 2007 Jan 20;357(2):186-98.
  16996101
• Kaur A, Sanford HB, Garry D, Lang S, Klumpp SA, Watanabe D, Bronson RT, Lifson JD, Rosati M, Pavlakis GN, Felber BK, Knipe DM, Desrosiers RC.Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge
  16962628
• Brockman MA, Verschoor A, Zhu J, Carroll MC, Knipe DM.Optimal long-term humoral responses to replication-defective herpes simplex virus require CD21/CD35 complement receptor expression on stromal cells.J Virol 2006 Jul;80(14):7111-7.
  16809316
• Palliser D, Chowdhury D, Wang QY, Lee SJ, Bronson RT, Knipe DM, Lieberman J.An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection.Nature 2006 Jan 5;439(7072):89-94.
  16306938
• Wakimoto H, Johnson PR, Knipe DM, Chiocca EA.Effects of innate immunity on herpes simplex virus and its ability to kill tumor cells.Gene Ther 2003 Jun;10(11):983-90.
  12756419
• de Bruyn Kops A, Uprichard SL, Chen M, Knipe DM.Comparison of the intranuclear distributions of herpes simplex virus proteins involved in various viral functions.Virology 1998 Dec 5;252(1):162-78.
  9875326
• Hann LE, Cook WJ, Uprichard SL, Knipe DM, Coen DM.The role of herpes simplex virus ICP27 in the regulation of UL24 gene expression by differential polyadenylation.J Virol 1998 Oct;72(10):7709-14.
  9733806
• Morrison LA, Da Costa XJ, Knipe DM.Influence of mucosal and parenteral immunization with a replication-defective mutant of HSV-2 on immune responses and protection from genital challenge.Virology 1998 Mar 30;243(1):178-87.
  9527927
• Kramer MF, Chen SH, Knipe DM, Coen DM.Accumulation of viral transcripts and DNA during establishment of latency by herpes simplex virus.J Virol 1998 Feb;72(2):1177-85.
  9445016
• Morrison LA, Knipe DM.Contributions of antibody and T cell subsets to protection elicited by immunization with a replication-defective mutant of herpes simplex virus type 1.Virology 1997 Dec 22;239(2):315-26.
  9434723
• Da Costa XJ, Bourne N, Stanberry LR, Knipe DM.Construction and characterization of a replication-defective herpes simplex virus 2 ICP8 mutant strain and its use in immunization studies in a guinea pig model of genital disease.Virology 1997 May 26;232(1):1
  9185583
• Brehm MA, Bonneau RH, Knipe DM, Tevethia SS.Immunization with a replication-deficient mutant of herpes simplex virus type 1 (HSV-1) induces a CD8+ cytotoxic T-lymphocyte response and confers a level of protection comparable to that of wild-type HSV-1.J Vi
  9094625
• Chen YM, Knipe DM.A dominant mutant form of the herpes simplex virus ICP8 protein decreases viral late gene transcription.Virology 1996 Jul 15;221(2):281-90.
  8661438
• Kanangat S, Babu JS, Knipe DM, Rouse BT.HSV-1-mediated modulation of cytokine gene expression in a permissive cell line: selective upregulation of IL-6 gene expression.Virology 1996 May 1;219(1):295-300.
  8623544
• Liptak LM, Uprichard SL, Knipe DM.Functional order of assembly of herpes simplex virus DNA replication proteins into prereplicative site structures.J Virol 1996 Mar;70(3):1759-67.
  8627698
• Uprichard SL, Knipe DM.Herpes simplex ICP27 mutant viruses exhibit reduced expression of specific DNA replication genes.J Virol 1996 Mar;70(3):1969-80.
  8627723
• Davar G, Kramer MF, Garber D, Roca AL, Andersen JK, Bebrin W, Coen DM, Kosz-Vnenchak M, Knipe DM, Breakefield XO.Comparative efficacy of expression of genes delivered to mouse sensory neurons with herpes virus vectors.J Comp Neurol 1994 Jan 1;339(1):3-11.
  8106660