Norbert J. Roberts, Jr., M.D.

"Respiratory viruses such as influenza and respiratory
syncytial virus reemerge and challenge us each year. There is
still much to be learned about their pathogenesis to facilitate
development of preventive or therapeutic measures."

Abbreviated Curriculum vitae

The Paul R. Stalnaker, MD Distinguished Professor of Internal Medicine
Professor of Microbiology and Immunology
Member, WHO Collaborating Center for Tropical Diseases

Chair, UTMB Multidisciplinary Task Force on Infectious Diseases and Host Defense
Program Director, UTMB Postdoctoral Training Program in Emerging and Reemerging Infectious Diseases

Education:

Board Certification:

Research Interests:

Viral pathogenesis; virus infection of leukocytes; influenza virus; respiratory syncytial virus (RSV).

Brief Description of Research:

Our research interests are in the area of human host defense mechanisms and viral pathogenesis, particularly the roles that mononuclear leukocytes (monocytes-macrophages and lymphocytes) play in antiviral defense. Our studies examine the regulatory roles of direct virus-cell and cell-cell interactions and cell-derived mediators (e.g., interleukins and interleukin inhibitors), and compare the functions and responses of different subpopulations of cells (e.g., autologous human alveolar and peripheral blood-derived macrophages and lymphocytes) in response to common challenges, such as influenza virus and respiratory syncytial virus (RSV).

Our particular interest is in the role of (and events during) active infection of the mononuclear leukocytes by virus in the course of a developing antiviral response, with attention to regulation of synthesis of viral and host gene products in the infected (and bystander) leukocytes that are recruited to defend against the virus. The correlation of ultimate antiviral immunologic responses (magnitude, kinetics, and repertoire) with the cellular and molecular events that occur immediately after exposure of leukocytes to the different viruses should help to delineate important mechanisms in the pathogenesis of viral infections and provide important insight for the design of viral vaccines or antiviral agents.

Current representative studies in the laboratory are delineating potential mechanisms through which RSV attenuates or delays the anamnestic immune response that would protect against clinical reinfection. We are also studying the basis for altered (reduced or absent) synthesis of influenza virus gene products by lymphocytes that show homozygous expression of certain HLA determinants.

Selected Publications (from over 100 papers published):

Original Scientific Articles:

• Roberts NJ Jr, Steigbigel RT: Effect of in vitro virus infection on response of human monocytes and lymphocytes to mitogen stimulation. J. Immunol. 121:1052-1058, 1978.

• Roberts NJ Jr, Douglas RG Jr, Simons RL, Diamond ME: Virus-induced interferon production by human macrophages. J. Immunol. 123:365-369, 1979.

• Chonmaitree T, Roberts NJ Jr, Douglas RG Jr, Hall CB, Simons RL: Interferon production by human mononuclear leukocytes: Differences between respiratory syncytial virus and influenza viruses. Infect. Immun. 32:300-303, 1981.

• Roberts NJ Jr: Different effects of influenza virus, respiratory syncytial virus and Sendai virus on human lymphocytes and macrophages. Infect. Immun. 35:1142-1146, 1982.

• Ettensohn DB, Roberts NJ Jr: Human alveolar macrophage support of lymphocyte responses to mitogens and antigens: Analysis and comparison with autologous peripheral blood-derived monocytes and macrophages. Am. Rev. Respir. Dis. 128:516-522, 1983.

• Bell DM, Roberts NJ Jr, Hall CB: Different antiviral spectra of human macrophage interferon activities. Nature 305:319-321, 1983.

• Ettensohn DB, Roberts NJ Jr: Influenza virus infection of human alveolar and blood-derived macrophages: Differences in accessory cell function and interferon production. J. Infect. Dis. 149:942-949, 1984.

• Jennings ST, Ettensohn DB, Roberts NJ Jr: Influenza virus infection of human alveolar and peripheral blood-derived macrophages: Production of factors that alter fibroblast proliferation. Am. Rev. Respir. Dis. 130:98-102, 1984.

• Roberts NJ Jr., Horan PK: Expression of viral antigens after infection of human lymphocytes,monocytes, and macrophages with influenza virus. J. Infect. Dis. 151:308-313, 1985.

• Domurat F, Roberts NJ Jr, Walsh EE, Dagan R: Respiratory syncytial virus infection of human mononuclear leukocytes in vitro and in vivo. J. Infect. Dis. 152:895-902, 1985.

• Roberts NJ Jr, Prill AH, Mann TN: Interleukin 1 and interleukin 1 inhibitor production by human macrophages exposed to influenza virus or respiratory syncytial virus: Respiratory syncytial virus is a potent inducer of inhibitory activity. J. Exp. Med. 163:511-519, 1986.

• Ettensohn DB, Lalor PA, Roberts NJ Jr: Human alveolar macrophage regulation of lymphocyte proliferation. Am. Rev. Respir. Dis. 133:1091-1096, 1986.

• Mock DJ, Domurat F, Roberts NJ Jr, Walsh EE, Licht MR, Keng P: Macrophages are required for influenza virus infection of human lymphocytes. J. Clin. Invest. 79:620-624, 1987.

• Gentry SE, Culp DJ, Roberts NJ Jr, Marin MG, Simons RL, Latchney LR: Influenza virus infection of tracheal gland cells in culture. J. Virol. 62:1524-1529, 1988.

• Roberts NJ Jr, Nichols JE: Regulation of proliferation after influenza virus infection of human mononuclear leukocytes. J. Med. Virol. 27:179-187, 1989.

• McCarthy DO, Domurat FM, Nichols JE, Roberts NJ Jr: Interleukin-1 inhibitor production by human mononuclear leukocytes and leukocyte subpopulations exposed to respiratory syncytial virus: Analysis and comparison with the response to influenza virus. J. Leuk. Biol. 46:189-198, 1989.

• Domurat FM, Keng P, Mock DJ, Prill AH, Roberts NJ Jr: Early identification and retrieval or deletion of human lymphocyte subpopulations responding to influenza virus or respiratory syncytial virus challenge. Cell Biophysics 15:173-188, 1989.

• Salkind AR, McCarthy DO, Nichols JE, Domurat FM, Walsh EE, Roberts NJ Jr: Interleukin-1 inhibitor activity induced by respiratory syncytial virus: Abrogation of virus-specific and alternate human lymphocyte proliferative responses. J. Infect. Dis. 163:71-77,1991.

• Keefer MC, Bonnez W, Roberts NJ Jr, Dolin R, Reichman RC: Human immunodeficiency virus (HIV-1) gp160-specific lymphocyte proliferative responses of peripheral blood mononuclear leukocytes from HIV-1 vaccine recipients. J. Infect. Dis. 163:448-453, 1991.

• Bonnez W, Reichman RC, Strussenberg J, Roberts NJ Jr: In vitro interactions between bovine papillomavirus and human monocytes/macrophages. Intervirology 32:246-252, 1991.

• Roberts NJ Jr, Hiscott J, Signs DJ: The limited interferon system response to respiratory syncytial virus challenge: Analysis and comparison to influenza virus. Microb. Pathogen. 12:409-414, 1992.

• Nichols JE, Mock DJ, Roberts NJ Jr: Use of FITC-labeled influenza virus and flow cytometry to assess binding and internalization of virus by monocytes-macrophages and lymphocytes. Arch. Virol. 130:441-455, 1992.

• Nichols JE, Fitzgerald TF, Roberts NJ Jr: Human macrophage responses to vaccine strains of influenza virus: synthesis of viral proteins, interleukin-1b, interleukin-6, tumour necrosis factor-a and interleukin-1b inhibitor. Vaccine 11:36-42, 1993.

• El-Daher N, Keefer MC, Reichman RC, Dolin R, Roberts NJ Jr: Persisting human immunodeficiency virus-1 gp160-specific human T lymphocyte responses including CD8+ cytotoxic activity after receipt of envelope vaccines. J. Infect. Dis. 168:306-313, 1993.

• DeSantis C, Robbioni P, Longhi R, Lopalco L, Siccardi AG, Beretta A, Roberts NJ Jr: Cross-reactive response to human immunodeficiency virus type 1 (HIV-1) gp120 and HLA class I heavy chains induced by receipt of HIV-1-derived envelope vaccines. J. Infect. Dis. 168:1396-1403, 1993.

• El-Daher N, Nichols JE, Roberts NJ Jr: Analysis of human antiviral cytotoxic T lymphocyte responses for vaccine trials using cryopreserved mononuclear leukocytes: Demonstration of feasibility with influenza virus-specific responses. Clin. Diag. Lab. Immunol. 1:487-492, 1994.

• Schuermann WHT, Frampton MW, Schuermann G, Roberts NJ Jr, Nichols JE, Finkelstein JN, Oberdorster G, Utell MJ: A flow cytometric assay of Fc receptor-mediated phagocytosis. J. Aerosol Med. 10:1-12, 1997.

• Frenkel LM, Mullins JI, Learn GH, Manns-Arcuino L, Herring BL, Kalish ML, Steketee RW, Thea DM, Nichols JE, Liu S-L, Harmache A, He X, Muthui D, Madan A, Hood L, Haase AT, Zupancic M, Staskus K, Wolinsky S, Krogstad P, Zhao J, Chen I, Koup R, Ho D, Korber B, Apple RJ, Coombs RW, Pawha S, Roberts NJ Jr: Genetic evaluation of suspected cases of transient HIV-1 infection of infants. Science 280:1073-1077, 1998.

• Frenkel LM, Mullins JI, Learn GH, Manns-Arcuino L, Herring BL, Kalish ML, Steketee RW, Thea DM, Nichols JE, Liu S-L, Harmache A, He X, Muthui D, Madan A, Hood L, Haase AT, Zupancic M, Staskus K, Wolinsky S, Krogstad P, Zhao J, Chen I, Koup R, Ho D, Korber B, Apple RJ, Coombs RW, Pawha S, Roberts NJ Jr: Genetic evaluation of suspected cases of transient HIV-1 infection of infants: Details of patients' clinical histories and laboratory studies. Science www.sciencemag.org/feature/data/974996.shl, 1998.

• Azadniv M, Utell MJ, Morrow PE, Gibb FR, Nichols JE, Roberts NJ Jr, Speers DM, Torres A, Tsai Y, Abraham MK, Voter KZ, Frampton MW: Effects of nitrogen dioxide exposure on human host defense. Inhalation Toxicology 10:585-601, 1998.

Contact Norbert J. Roberts, Jr., MD, via E-mail: njroberts@utmb.edu