Research Summary

My research focus is investigation of the interactions of human viruses, including human cytomegalovirus (HCMV), Epstein–Barr virus (EBV), Herpes simplex virus (HSV), human immunodeficiency virus (HIV), and human papillomavirus (HPV), with monostratified and multistratified oral epithelia. We have made significant contributions to current knowledge about entry, transcytosis, intracellular transport, egress, and cell-to-cell transmission of these viruses in oral epithelial cells by establishing and using polarized epithelial cells, as well as ex vivo oral mucosal tissue explants. Currently, we are investigating the potential interactions of HIV with other viral pathogens, including human papillomavirus HPV. The incidence of HPV-associated oral cancer in human immunodeficiency virus (HIV)-positive individuals is substantially higher than in HIV-uninfected individuals. Our data show that oral epithelial biopsies from HIV-infected individuals and oral keratinocytes grown in tissue culture from HIV-infected individuals have multiple changes consistent with epithelial-mesenchymal transition (EMT), a multistep epigenetic process characterized by loss of cell adhesion and increased proliferation and mobility of epithelial cells. EMT is important in cell differentiation during embryogenesis. However, it is also plays a critical role in progression of neoplastic processes. We expect that our research may led to better understanding the role of HIV-associated EMT in development of HPV-associated neoplasia.

Research Funding

  • December 1, 2018 - November 30, 2023 - Role of HIV in acceleration of HPV malignancy , Principal Investigator . Sponsor: NIH/NCI, Sponsor Award ID: R01CA232887
  • September 6, 2018 - June 30, 2023 - Role of oral herpesvirus microbiota in pathogenesis of HIV mother to child transmission , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DE028129
  • May 1, 2013 - March 31, 2019 - Molecular mechanisms of oral HIV transmission modeling MTCT , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DE023315
  • July 2, 2010 - June 30, 2013 - HIV transcellular and transsynaptic penetration of mucosal epithelium , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21DE021011

Education

Institute of Agriculture, School of Veterinary Medicine, Samarkand, Uzbekistan (former Soviet Union), DVM 1981, Veterinary Medicine
Institute of Experimental Veterinary Medicine and Ivanosky Institute of Virology, Moscow, Russia, PhD, 1985, Virology, Cell Biology
Ivanosky Institute of Virology, Russian Academy of Medical Sciences, Moscow, Russia, DSc, 1996, Medical Virology Infectious Disease

Selected Publications

  1. Tugizov SM. Molecular Pathogenesis of Human Immunodeficiency Virus-Associated Disease of Oropharyngeal Mucosal Epithelium. Biomedicines. 2023 May 14; 11(5).  View on PubMed
  2. Walston JJ, Hayman IR, Gore M, Ferguson M, Temple RM, Liao J, Alam S, Meyers C, Tugizov SM, Hutt-Fletcher L, Sample CE. The Epstein-Barr Virus Glycoprotein BDLF2 Is Essential for Efficient Viral Spread in Stratified Epithelium. J Virol. 2023 02 28; 97(2):e0152822.  View on PubMed
  3. Lien K, Mayer W, Herrera R, Padilla NT, Cai X, Lin V, Pholcharoenchit R, Palefsky J, Tugizov SM. HIV-1 Proteins gp120 and Tat Promote Epithelial-Mesenchymal Transition and Invasiveness of HPV-Positive and HPV-Negative Neoplastic Genital and Oral Epithelial Cells. Microbiol Spectr. 2022 12 21; 10(6):e0362222.  View on PubMed
  4. Herrera R, Rosbe K, Tugizov SM. Inactivation of HIV-1 in Polarized Infant Tonsil Epithelial Cells by Human Beta-Defensins 2 and 3 Tagged with the Protein Transduction Domain of HIV-1 Tat. Viruses. 2021 10 11; 13(10).  View on PubMed
  5. Sufiawati I, Herrera R, Mayer W, Cai X, Borkakoti J, Lin V, Rosbe K, Tugizov SM. Human Immunodeficiency Virus (HIV) and Human Cytomegalovirus (HCMV) Coinfection of Infant Tonsil Epithelium May Synergistically Promote both HIV-1 and HCMV Spread and Infection. J Virol. 2021 08 25; 95(18):e0092121.  View on PubMed
  6. Tugizov S. Virus-associated disruption of mucosal epithelial tight junctions and its role in viral transmission and spread. Tissue Barriers. 2021 10 02; 9(4):1943274.  View on PubMed
  7. Tugizov SM. Human immunodeficiency virus interaction with oral and genital mucosal epithelia may lead to epithelial-mesenchymal transition and sequestration of virions in the endosomal compartments. Oral Dis. 2020 Sep; 26 Suppl 1:40-46.  View on PubMed
  8. Weinberg A, Tugizov S, Pandiyan P, Jin G, Rakshit S, Vyakarnam A, Naglik JR. Innate immune mechanisms to oral pathogens in oral mucosa of HIV-infected individuals. Oral Dis. 2020 Sep; 26 Suppl 1:69-79.  View on PubMed
  9. Lien K, Mayer W, Herrera R, Rosbe K, Tugizov SM. HIV-1 proteins gp120 and tat induce the epithelial-mesenchymal transition in oral and genital mucosal epithelial cells. PLoS One. 2019; 14(12):e0226343.  View on PubMed
  10. Walhart T, Isaacson-Wechsler E, Ang KH, Arkin M, Tugizov S, Palefsky JM. A Cell-Based Renilla Luminescence Reporter Plasmid Assay for High-Throughput Screening to Identify Novel FDA-Approved Drug Inhibitors of HPV-16 Infection. SLAS Discov. 2020 01; 25(1):79-86.  View on PubMed
  11. Wechsler EI, Tugizov S, Herrera R, Costa MD, Palefsky JM. Erratum: E5 can be expressed in anal cancer and leads to epidermal growth factor receptor-induced invasion in a human papillomavirus 16-transformed anal epithelial cell line. J Gen Virol. 2018 07; 99(7):948.  View on PubMed
  12. Sufiawati I, Tugizov SM. HIV-induced matrix metalloproteinase-9 activation through mitogen-activated protein kinase signalling promotes HSV-1 cell-to-cell spread in oral epithelial cells. J Gen Virol. 2018 07; 99(7):937-947.  View on PubMed
  13. Wechsler EI, Tugizov S, Herrera R, Da Costa M, Palefsky JM. E5 can be expressed in anal cancer and leads to epidermal growth factor receptor-induced invasion in a human papillomavirus 16-transformed anal epithelial cell line. J Gen Virol. 2018 05; 99(5):631-644.  View on PubMed
  14. Yasen A, Herrera R, Rosbe K, Lien K, Tugizov SM. HIV internalization into oral and genital epithelial cells by endocytosis and macropinocytosis leads to viral sequestration in the vesicles. Virology. 2018 02; 515:92-107.  View on PubMed
  15. Yasen A, Herrera R, Rosbe K, Lien K, Tugizov SM. Release of HIV-1 sequestered in the vesicles of oral and genital mucosal epithelial cells by epithelial-lymphocyte interaction. PLoS Pathog. 2017 02; 13(2):e1006247.  View on PubMed
  16. Haga T, Efird JT, Tugizov S, Palefsky JM. Increased TNF-alpha and sTNFR2 levels are associated with high-grade anal squamous intraepithelial lesions in HIV-positive patients with low CD4 level. Papillomavirus Res. 2017 Jun; 3:1-6.  View on PubMed
  17. Tugizov S. Human immunodeficiency virus-associated disruption of mucosal barriers and its role in HIV transmission and pathogenesis of HIV/AIDS disease. Tissue Barriers. 2016 Jul-Sep; 4(3):e1159276.  View on PubMed
  18. Herrera R, Morris M, Rosbe K, Feng Z, Weinberg A, Tugizov S. Human beta-defensins 2 and -3 cointernalize with human immunodeficiency virus via heparan sulfate proteoglycans and reduce infectivity of intracellular virions in tonsil epithelial cells. Virology. 2016 Jan; 487:172-87.  View on PubMed
  19. Sufiawati I, Tugizov SM. HIV-associated disruption of tight and adherens junctions of oral epithelial cells facilitates HSV-1 infection and spread. PLoS One. 2014; 9(2):e88803.  View on PubMed
  20. Tugizov SM, Herrera R, Chin-Hong P, Veluppillai P, Greenspan D, Michael Berry J, Pilcher CD, Shiboski CH, Jay N, Rubin M, Chein A, Palefsky JM. HIV-associated disruption of mucosal epithelium facilitates paracellular penetration by human papillomavirus. Virology. 2013 Nov; 446(1-2):378-88.  View on PubMed

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