Contributions to Science

  1. We determined the first HIV-1 sequence and constructed and characterized the first infectious molecular clones of HIV-1, -2, and HTLV-1.
    1. Ratner L, Haseltine W, Patarca R, Livak KJ, Starcich B, et al. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24-30;313(6000):277-84. PubMed PMID: 2578615.
    2. Fisher AG, Collalti E, Ratner L, Gallo RC, Wong-Staal F. A molecular clone of HTLV-III with biological activity. Nature. 1985 Jul 18-24;316(6025):262-5. PubMed PMID: 2410792.
    3. Hu W, Vander Heyden N, Ratner L. Analysis of the function of viral protein X (VPX) of HIV-2. Virology. 1989 Dec;173(2):624-30. PubMed PMID: 2596032.
    4. Kimata JT, Wong FH, Wang JJ, Ratner L. Construction and characterization of infectious human T-cell leukemia virus type 1 molecular clones. Virology. 1994 Nov 1;204(2):656-64. PubMed PMID: 7941334.
  2. We demonstrated the key role of nuclear factor kappa B signaling and role of chromatin barrier element, CTCF, in HTLV-1-associated replication and transformation.
    1. Cherian M, Baydoun H, Al-Saleem J, Kvaratskhelia M, Green P, Ratner L. Akt activation by human T-cell leukemia virus Tax oncoprotein. Journal of Biological Chemistry 2015, 290:26270-26281. PMID:26324707.
    2. Cherian MA, Olson S, Cates K, Sundaramoorthi H, Cheng X, Harding J, Martens A, Challen GA, Tyagi M, Ratner L, Rauch D. An activating mutation of interferon regulatory factor 4 in adult T cell leukemia, Journal of Biological Chemistry, 2018 May 4;293(18):6844-6858. PMID: 29540473
    3. Xiang J*, Rauch D*, Huey D, Panfil A, Cheng X, Esser A, Su X, Harding J, Xu Y, Fox G, Fontana F, Kobayashi T, Su J, Sundaramoorthi H, Wong W, Jia Y, Rosol T, Veis D, Green P, Niewiesk S, Ratner L, Weilbaecher K. HTLV-1 viral oncogene HBZ drives bone destruction in adult T-cell leukemia. Journal of Clinical Investigation Insight. 2019. 4(19): e128713. PMID:31578308 PMCID:PMC6795409
    4. Cheng X, Joseph A, Castro V, Chen-liaw A, Skidmore Z, Ueno T, Fujisawa J-I, Rauch DA, Challen G, Martinez MP Green P, Griffith M, Payton JE, Edwards J, Ratner L. CTCF regulation of HTLV-1 DNA methylation and gene expression. PLoS Pathogens. 2021. 17:e1009577. PMID: 34019588
  3. We characterized the role of accessory gene products of HIV-1 and HTLV-1 and their roles in latency.
    1. Cheng X, Ratner L. HIV-2 Vpx protein interacts with interferon regulatory factor 5 (IRF5) and inhibits its function. Journal of Biological Chemistry. 2014 Mar 28;289(13):9146-57. PubMed PMID: 24532789; PubMed Central PMCID: PMC3979364.
    2. Kyei GB, Cheng X, Ramani R, Ratner L. Cyclin L2 Is a Critical HIV Dependency Factor in Macrophages that Controls SAMHD1 Abundance. Cell Host & Microbe. 2015 Jan 14;17(1):98-106. PubMed PMID: 25532805; PubMed Central PMCID: PMC4297224.
    3. Albert B, Niu A, Ramani R, Williams RM, Marshall GR, Wender P, Williams RM, Ratner L, Barnes AB, Kyei G. Combinations of isoform-targeted histone deacetylase inhibitors and bryostatin analogues display remarkable potency to activate latent HIV without global T-cell activation, Science Reports, 2017; 7:7456.  PMID:28785069; PMCID: PMC5547048
    4. Kisaka JK. Ratner L, Kyei GB. The dual-specificity kinase DYRK1A modulates the levels of cyclin L2 to control HIV replication in macrophages. Journal of Virology, 2020; 94:e01583-19. PMID: 31852782. PMCID: PMC7158737
  4. We demonstrated a key role of cell signaling in HIV-1 entry.
    1. Harmon B, Campbell N, Ratner L. Role of Abl kinase and the Wave2 signaling complex in HIV-1 entry at a post-hemifusion step. PLoS Pathogens. 2010 Jun 17;6(6):e1000956. PubMed PMID: 20585556; PubMed Central PMCID: PMC2887473.
    2. Zhang J, Gao X, Martin J, Rosa B, Chen Z, Mitreva M, Henrich T, Kuritzkes D, Ratner L. Evolution of coreceptor utilization to escape CCR5 antagonist therapy. Virology, 2016 494:198-214, PMID:27128349
    3. Wu E, Du Y, Gao X, Zhang J, Martin J, Mitreva M, Ratner L. 2019. V1 and V2 domains of HIV envelope contribute to CCR5 antagonist resistance. J Virology, 93:e00050-19. PMID: 30787151. PMC6475789
    4. Du Y, Wu E, Gao X, Zhang J, Martin JC, Rosa B, Mitreva M, Ratner L. 2022. HIV-1 envelope sequence evolution with co-receptor antagonism. Microbiology Spectrum, 10:e0072522. PMID:35727047.
  5. We led translational studies to improve therapies for HIV-1- and HTLV-1-associated malignancies.
    1. Ratner L, Harrington W, Feng X, Grant C, Jacobson S, et al. Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma. PLoS One. 2009;4(2):e4420. PubMed PMID: 19204798; PubMed Central PMCID: PMC2636875.
    2. Ratner L, Rauch D, Abel H, Caruso B, Baydoun HH, Noy A, Barta SK, Parekh S, Ramos JC, Ambinder R, Phillips A, Harding J, Cheng X, Jacobson S. 2016. Dose-adjusted EPOCH chemotherapy with bortezomib and raltegravir for human T-cell leukemia virus-associated T-cell leukemia lymphoma. Blood Cancer Journal, 6:e408, PMID:27015285
    3. Ratner L, Waldmann TA, Janakiram M, Brammer J. 2018. PD-1 inhibition promotes rapid adult T cell leukemia progression. N Engl J Med, 378:1947-1948, PMID: 29768155; Response by Ratner L, New England Journal of Medicine, 379:696-697 PMID:30110590
    4. Rauch DA, Conlon KC, Janakiram M, Brammer JE, Harding JC, Ye BH, Xang XX, Ren X, Olson S, Cheng X, Miljkovic MD, Sundaramoorthi H, Joseph A, Skidmore JL, Griffith O, Griffith M, Waldmann TA, Ratner L. 2019. Rapid progression of adult T-cell leukemia/lymphoma as tumor infiltrating Treg cells after PD-1 blockade. Blood, 134(17):1406-1414. PMID: 31467059