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Tatyana Golovkina

TitleProfessor
InstitutionUniversity of Chicago
DepartmentMicrobiology
AddressChicago IL 60637
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    Collapse Overview 
    Collapse overview
    The primary goal of my laboratory is to understand how the innate immune system detects retroviral infection and initiates virus-neutralizing adaptive immune responses. In addition, we are also interested in mechanisms evolved by retroviruses to overcome host protective responses. To investigate these important questions, we employ virus-resistant mice capable of controlling retroviruses from distinct genera. As is the case with other researchers who utilize mouse models to study either human or mouse pathogens, we trust that the data we generate will ultimately further our understanding of the progression and resolution of human disease. Using mice from retrovirus-resistant strains, we found that endosomal Toll-like receptor 7 (TLR7) is an innate immune receptor that detects mouse retroviruses and signals to stimulate the production of virus- neutralizing antibodies (Kane et al, Immunity 2011). The same innate mechanism was shown to detect Human Immunodeficiency Virus 1 (HIV-1).

    Most viruses enter the host through surfaces exposed to the microbiota that protect the host from incoming pathogens. We performed pioneering work showing that orally transmitted retroviruses exploit the microbiota for their own benefit (Kane et al, Science 2011). The enveloped retrovirus, MMTV acquires host Lipopolysaccharide (LPS)-binding factors during budding to bind LPS produced by Gram-negative commensal bacteria (Wilks et al, Cell Host and Microbe 2015). Virion-associated LPS activates Toll-like receptor 4 (TLR4), stimulating production of the immunosuppressive cytokine IL-10 and virus evasion of the host immune response (Kane et al, Science, 2011). Julie Pfeiffer’s group simultaneously showed that picornavirus and reovirus transmission also depends on the gut microbiota. Noroviruses and rotaviruses have been recently added to the list of viruses known to require the gut microbiota for successful transmission, further supporting the idea that mouse models lead to fundamental discoveries.

    Retroviruses earned their notoriety by inducing a broad range of tumors in vertebrates. Whereas some retroviruses carry oncogenes in their genome, the vast majority of retroviruses do not encode such elements and thus, must integrate near cellular proto-oncogenes and up-regulate them to induce tumors. Many cellular genes involved in tumorigenesis were first identified as viral oncogenes (v-onc) or genes up-regulated upon retroviral insertion. They are now known to be involved in various types of spontaneous tumors in humans. Up-regulation of cellular protooncogenes via insertional mutagenesis or insertion of v-oncs constitutes a necessary step for tumor induction. However, up-regulation of an oncogene alone is not sufficient for tumor induction and other events are required for tumor development. We have found that the gut commensal bacteria serve as an epigenetic factor that contributes to virally-induced cancer. Using well-defined animal models of virally-induced leukemogenesis we are searching for the mechanism(s) by which the commensal microbiota promotes virally-induced tumorigenesis.

    All animals, including humans, show different susceptibility to infectious retroviruses. Mice of the I/LnJ strain control both gamma- and betaretroviruses via the same recessive immune mechanism, which involves production of virus-neutralizing antibodies (Abs)
    (Purdy et al, J Exp Med 2003; Case et al, J Immunol 2005; Case et al, J Virol 2007). Even though I/LnJ mice become infected with both viruses, they produce anti-virus Abs which coat virions, rendering them uninfectious. As a consequence, retroviruses are eliminated from infected mice. The retrovirus resistance mechanism in I/LnJ mice is controlled by a single locus, virus infectivity controller 1 (vic1), that we mapped to Chromosome 17 (Case et a., J Virol, 2007). A non-classical major histocompatibility class II (MHCII) gene, H2-Ob (Ob), an inhibitor of antigen presentation was identified as the gene encoding for Vic1 (Denzin et. al, 2017, Immunity 47, 310-322). Subsequent bioinformatics and functional analyses of the human H2-Ob homologue, HLA-DOB revealed both loss- and gain-of-function alleles, which could affect the ability of their carriers to control infections with Human Hepatitis B (HBV) and C (HCV) viruses. Thus, understanding of the previously unappreciated role of H2-O (HLA-DO) in immunity to infections may suggest new approaches in achieving neutralizing immunity to viruses.


    Collapse Biography 
    Collapse education and training
    Moscow State University, Moscow, Former USSRPhD06/1985Biochemistry, Virology
    Collapse awards and honors
    1987Prize of All-Union Young Scientists competition (together with S.V. Litvinov)
    1993 - 1995Cancer Research Institute Postdoctoral Fellowship Award
    1997V Foundation Scholar
    2000Cancer Research Institute (CRI) 2000 Hillsdale Fund, Inc. Greensboro, N.C.
    2000Oliver and Jennie Donaldson Charitable Trust
    2018Fellow of the American Academy of Microbiology
    2019Fellow of American Association for the Advancement of Science

    Collapse ORNG Applications 
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    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Khan AA, Yurkovetskiy L, O'Grady K, Pickard JM, de Pooter R, Antonopoulos DA, Golovkina T, Chervonsky A. Polymorphic Immune Mechanisms Regulate Commensal Repertoire. Cell Rep. 2019 Oct 15; 29(3):541-550.e4. PMID: 31618625.
      View in: PubMed
    2. Kane M, Golovkina TV. Mapping Viral Susceptibility Loci in Mice. Annu Rev Virol. 2019 Sep 29; 6(1):525-546. PMID: 31567067.
      View in: PubMed
    3. Kane M, Deiss F, Chervonsky A, Golovkina TV. A Single Locus Controls Interferon Gamma-Independent Antiretroviral Neutralizing Antibody Responses. J Virol. 2018 08 15; 92(16). PMID: 29875252.
      View in: PubMed
    4. Denzin LK, Khan AA, Virdis F, Wilks J, Kane M, Beilinson HA, Dikiy S, Case LK, Roopenian D, Witkowski M, Chervonsky AV, Golovkina TV. Neutralizing Antibody Responses to Viral Infections Are Linked to the Non-classical MHC Class II Gene H2-Ob. Immunity. 2017 08 15; 47(2):310-322.e7. PMID: 28813660.
      View in: PubMed
    5. Dudley JP, Golovkina TV, Ross SR. Lessons Learned from Mouse Mammary Tumor Virus in Animal Models. ILAR J. 2016; 57(1):12-23. PMID: 27034391.
      View in: PubMed
    6. Wilks J, Lien E, Jacobson AN, Fischbach MA, Qureshi N, Chervonsky AV, Golovkina TV. Mammalian Lipopolysaccharide Receptors Incorporated into the Retroviral Envelope Augment Virus Transmission. Cell Host Microbe. 2015 Oct 14; 18(4):456-62. PMID: 26468748.
      View in: PubMed
    7. Wilks J, Golovkina T. Immunology. Interfering with interferons. Science. 2015 Jan 16; 347(6219):233-4. PMID: 25593173.
      View in: PubMed
    8. Pickard JM, Maurice CF, Kinnebrew MA, Abt MC, Schenten D, Golovkina TV, Bogatyrev SR, Ismagilov RF, Pamer EG, Turnbaugh PJ, Chervonsky AV. Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness. Nature. 2014 Oct 30; 514(7524):638-41. PMID: 25274297.
      View in: PubMed
    9. Liarski VM, Kaverina N, Chang A, Brandt D, Yanez D, Talasnik L, Carlesso G, Herbst R, Utset TO, Labno C, Peng Y, Jiang Y, Giger ML, Clark MR. Cell distance mapping identifies functional T follicular helper cells in inflamed human renal tissue. Sci Transl Med. 2014 Apr 02; 6(230):230ra46. PMID: 24695686.
      View in: PubMed
    10. Wilks J, Beilinson H, Theriault B, Chervonsky A, Golovkina T. Antibody-mediated immune control of a retrovirus does not require the microbiota. J Virol. 2014 Jun; 88(11):6524-7. PMID: 24648456.
      View in: PubMed
    11. Wilks J, Beilinson H, Golovkina TV. Dual role of commensal bacteria in viral infections. Immunol Rev. 2013 Sep; 255(1):222-9. PMID: 23947358.
      View in: PubMed
    12. Beyer AR, Bann DV, Rice B, Pultz IS, Kane M, Goff SP, Golovkina TV, Parent LJ. Nucleolar trafficking of the mouse mammary tumor virus gag protein induced by interaction with ribosomal protein L9. J Virol. 2013 Jan; 87(2):1069-82. PMID: 23135726.
      View in: PubMed
    13. Kane M, Golovkina T. Realities of virus sensing. Microbes Infect. 2012 Oct; 14(12):1017-25. PMID: 22750677.
      View in: PubMed
    14. Wilks J, Golovkina T. Influence of microbiota on viral infections. PLoS Pathog. 2012; 8(5):e1002681. PMID: 22615558.
      View in: PubMed
    15. Kane M, Case LK, Kopaskie K, Kozlova A, MacDearmid C, Chervonsky AV, Golovkina TV. Successful transmission of a retrovirus depends on the commensal microbiota. Science. 2011 Oct 14; 334(6053):245-9. PMID: 21998394.
      View in: PubMed
    16. Kane M, Case LK, Wang C, Yurkovetskiy L, Dikiy S, Golovkina TV. Innate immune sensing of retroviral infection via Toll-like receptor 7 occurs upon viral entry. Immunity. 2011 Jul 22; 35(1):135-45. PMID: 21723157.
      View in: PubMed
    17. Kane M, Case LK, Golovkina TV. Vital role for CD8+ cells in controlling retroviral infections. J Virol. 2011 Apr; 85(7):3415-23. PMID: 21248041.
      View in: PubMed
    18. Kane M, Golovkina T. Common threads in persistent viral infections. J Virol. 2010 May; 84(9):4116-23. PMID: 19955304.
      View in: PubMed
    19. Case LK, Petell L, Yurkovetskiy L, Purdy A, Savage KJ, Golovkina TV. Replication of beta- and gammaretroviruses is restricted in I/LnJ mice via the same genetic mechanism. J Virol. 2008 Feb; 82(3):1438-47. PMID: 18057254.
      View in: PubMed
    20. Swanson I, Jude BA, Zhang AR, Pucker A, Smith ZE, Golovkina TV. Sequences within the gag gene of mouse mammary tumor virus needed for mammary gland cell transformation. J Virol. 2006 Apr; 80(7):3215-24. PMID: 16537589.
      View in: PubMed
    21. MacDearmid CC, Case LK, Starling CL, Golovkina TV. Gradual elimination of retroviruses in YBR/Ei mice. J Virol. 2006 Mar; 80(5):2206-15. PMID: 16474128.
      View in: PubMed
    22. Case LK, Purdy A, Golovkina TV. Molecular and cellular basis of the retrovirus resistance in I/LnJ mice. J Immunol. 2005 Dec 01; 175(11):7543-9. PMID: 16301663.
      View in: PubMed
    23. Pobezinskaya Y, Chervonsky AV, Golovkina TV. Initial stages of mammary tumor virus infection are superantigen independent. J Immunol. 2004 May 01; 172(9):5582-7. PMID: 15100301.
      View in: PubMed
    24. Sarkar NH, Golovkina T, Uz-Zaman T. RIII/Sa mice with a high incidence of mammary tumors express two exogenous strains and one potential endogenous strain of mouse mammary tumor virus. J Virol. 2004 Jan; 78(2):1055-62. PMID: 14694140.
      View in: PubMed
    25. Rankin EB, Yu D, Jiang J, Shen H, Pearce EJ, Goldschmidt MH, Levy DE, Golovkina TV, Hunter CA, Thomas-Tikhonenko A. An essential role of Th1 responses and interferon gamma in infection-mediated suppression of neoplastic growth. Cancer Biol Ther. 2003 Nov-Dec; 2(6):687-93. PMID: 14688478.
      View in: PubMed
    26. Jude BA, Pobezinskaya Y, Bishop J, Parke S, Medzhitov RM, Chervonsky AV, Golovkina TV. Subversion of the innate immune system by a retrovirus. Nat Immunol. 2003 Jun; 4(6):573-8. PMID: 12730691.
      View in: PubMed
    27. Purdy A, Case L, Duvall M, Overstrom-Coleman M, Monnier N, Chervonsky A, Golovkina T. Unique resistance of I/LnJ mice to a retrovirus is due to sustained interferon gamma-dependent production of virus-neutralizing antibodies. J Exp Med. 2003 Jan 20; 197(2):233-43. PMID: 12538662.
      View in: PubMed
    28. Hook LM, Jude BA, Ter-Grigorov VS, Hartley JW, Morse HC, Trainin Z, Toder V, Chervonsky AV, Golovkina TV. Characterization of a novel murine retrovirus mixture that facilitates hematopoiesis. J Virol. 2002 Dec; 76(23):12112-22. PMID: 12414952.
      View in: PubMed
    29. Hunter CA, Yu D, Gee M, Ngo CV, Sevignani C, Goldschmidt M, Golovkina TV, Evans S, Lee WF, Thomas-Tikhonenko A. Cutting edge: systemic inhibition of angiogenesis underlies resistance to tumors during acute toxoplasmosis. J Immunol. 2001 May 15; 166(10):5878-81. PMID: 11342601.
      View in: PubMed
    30. Golovkina T, Agafonova Y, Kazansky D, Chervonsky A. Diverse repertoire of the MHC class II-peptide complexes is required for presentation of viral superantigens. J Immunol. 2001 Feb 15; 166(4):2244-50. PMID: 11160278.
      View in: PubMed
    31. Hook LM, Agafonova Y, Ross SR, Turner SJ, Golovkina TV. Genetics of mouse mammary tumor virus-induced mammary tumors: linkage of tumor induction to the gag gene. J Virol. 2000 Oct; 74(19):8876-83. PMID: 10982330.
      View in: PubMed
    32. Golovkina TV. A novel mechanism of resistance to mouse mammary tumor virus infection. J Virol. 2000 Mar; 74(6):2752-9. PMID: 10684291.
      View in: PubMed
    33. Golovkina TV, Shlomchik M, Hannum L, Chervonsky A. Organogenic role of B lymphocytes in mucosal immunity. Science. 1999 Dec 03; 286(5446):1965-8. PMID: 10583962.
      View in: PubMed
    34. Dzuris JL, Zhu W, Kapkov D, Golovkina TV, Ross SR. Expression of mouse mammary tumor virus envelope protein does not prevent superinfection in vivo or in vitro. Virology. 1999 Oct 25; 263(2):418-26. PMID: 10544114.
      View in: PubMed
    35. Qin W, Golovkina TV, Peng T, Nepomnaschy I, Buggiano V, Piazzon I, Ross SR. Mammary gland expression of mouse mammary tumor virus is regulated by a novel element in the long terminal repeat. J Virol. 1999 Jan; 73(1):368-76. PMID: 9847341.
      View in: PubMed
    36. Golovkina TV, Dudley JP, Ross SR. B and T cells are required for mouse mammary tumor virus spread within the mammary gland. J Immunol. 1998 Sep 01; 161(5):2375-82. PMID: 9725233.
      View in: PubMed
    37. Golovkina TV, Dzuris J, van den Hoogen B, Jaffe AB, Wright PC, Cofer SM, Ross SR. A novel membrane protein is a mouse mammary tumor virus receptor. J Virol. 1998 Apr; 72(4):3066-71. PMID: 9525630.
      View in: PubMed
    38. Dzuris JL, Golovkina TV, Ross SR. Both T and B cells shed infectious mouse mammary tumor virus. J Virol. 1997 Aug; 71(8):6044-8. PMID: 9223496.
      View in: PubMed
    39. Golovkina TV, Piazzon I, Nepomnaschy I, Buggiano V, de Olano Vela M, Ross SR. Generation of a tumorigenic milk-borne mouse mammary tumor virus by recombination between endogenous and exogenous viruses. J Virol. 1997 May; 71(5):3895-903. PMID: 9094666.
      View in: PubMed
    40. Ross SR, Dzuris JL, Golovkina TV, Clemmons WC, van den Hoogen B. Mouse mammary tumor virus (MMTV), a retrovirus that exploits the immune system. Genetics of susceptibility to MMTV infection. Medicina (B Aires). 1997; 57 Suppl 2:34-42. PMID: 9567342.
      View in: PubMed
    41. Golovkina TV, Prakash O, Ross SR. Endogenous mouse mammary tumor virus Mtv-17 is involved in Mtv-2-induced tumorigenesis in GR mice. Virology. 1996 Apr 01; 218(1):14-22. PMID: 8615016.
      View in: PubMed
    42. Chervonsky AV, Golovkina TV, Ross SR, Janeway CA. Differences in the avidity of TCR interactions with a superantigenic ligand affect negative selection but do not allow positive selection. J Immunol. 1995 Dec 01; 155(11):5115-23. PMID: 7594520.
      View in: PubMed
    43. Golovkina TV, Dudley JP, Jaffe AB, Ross SR. Mouse mammary tumor viruses with functional superantigen genes are selected during in vivo infection. Proc Natl Acad Sci U S A. 1995 May 23; 92(11):4828-32. PMID: 7761408.
      View in: PubMed
    44. Golovkina TV, Jaffe AB, Ross SR. Coexpression of exogenous and endogenous mouse mammary tumor virus RNA in vivo results in viral recombination and broadens the virus host range. J Virol. 1994 Aug; 68(8):5019-26. PMID: 8035502.
      View in: PubMed
    45. Golovkina TV, Chervonsky A, Prescott JA, Janeway CA, Ross SR. The mouse mammary tumor virus envelope gene product is required for superantigen presentation to T cells. J Exp Med. 1994 Feb 01; 179(2):439-46. PMID: 8294859.
      View in: PubMed
    46. Golovkina TV, Prescott JA, Ross SR. Mouse mammary tumor virus-induced tumorigenesis in sag transgenic mice: a laboratory model of natural selection. J Virol. 1993 Dec; 67(12):7690-4. PMID: 8230492.
      View in: PubMed
    47. Mok E, Golovkina TV, Ross SR. A mouse mammary tumor virus mammary gland enhancer confers tissue-specific but not lactation-dependent expression in transgenic mice. J Virol. 1992 Dec; 66(12):7529-32. PMID: 1331537.
      View in: PubMed
    48. Golovkina TV, Chervonsky A, Dudley JP, Ross SR. Transgenic mouse mammary tumor virus superantigen expression prevents viral infection. Cell. 1992 May 15; 69(4):637-45. PMID: 1316806.
      View in: PubMed
    49. Tikhonenko AT, Polotskaya AV, Vassetzky NS, Golovkina TV, Gudkov AV. Long terminal repeats of dwarf hamster endogenous retrovirus are highly diverged and do not maintain efficient transcription. Virology. 1991 Mar; 181(1):367-70. PMID: 1994585.
      View in: PubMed
    50. Golovkina TV, Tikhonenko AT, Vassetzky NS, Sheftel BI, Gudkov AV. Distribution of mouse mammary tumor virus-related sequences does not correlate with the taxonomic position of their hosts. Virus Genes. 1990 Jun; 4(1):85-92. PMID: 2168108.
      View in: PubMed
    51. Tikhonenko AT, Vassetzky NS, Golovkina TV, Gudkov AV. Molecular cloning and primary structure analysis of the mouse mammary tumor virus-related element from dwarf hamster genome. Virus Genes. 1990 Feb; 3(3):259-61. PMID: 2161160.
      View in: PubMed
    52. Golovkina TV, Tikhonenko AT, Vasetskii NS, Sheftel' BI, Gudkov AV. [Sequences homologous to mouse mammary cancer virus are common in mammalian and avian genomes]. Mol Biol (Mosk). 1990 Jan-Feb; 24(1):127-33. PMID: 2161490.
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    53. Vasetskii NS, Tikhonenko AT, Golovkina TV, Gudkov AV. [Cloning and analysis of the primary structure of an element, related to the murine mammary cancer virus, from the genome of the Djungarian hamster]. Mol Gen Mikrobiol Virusol. 1989 Oct; (10):16-9. PMID: 2559324.
      View in: PubMed
    54. Litvinov SV, Golovkina TV. Expression of proteins immunologically related to murine mammary tumour virus (MMTV) core proteins in the cells of breast cancer continuous lines MCF-7, T47D, MDA-231 and cells from human milk. Acta Virol. 1989 Mar; 33(2):137-42. PMID: 2569809.
      View in: PubMed
    55. Litvinov SV, Golovkina TV, Kriukova IN, Vasilevskaia LN. [A protein related to the main core protein of the mouse mammary cancer virus in a microparticle fraction of human milk]. Biull Eksp Biol Med. 1987 Mar; 103(3):338-40. PMID: 3030463.
      View in: PubMed
    56. Vaisman BL, Kolobkov SL, Sorokin AV, Dolzhanskaia NB, Golovkina TV. [Effect of v-sis-oncogene on transgenic mice]. Dokl Akad Nauk SSSR. 1987; 294(5):1225-8. PMID: 3040361.
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    57. Litvinov SV, Golovkina TV. [Expression of antigens related to structural protein antigens of MMTV in breast cancer cells]. Vopr Onkol. 1985; 31(7):47-53. PMID: 2411055.
      View in: PubMed
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