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Michael D. Weiden

Michael D. Weiden, MD

Professor, Department of Medicine

Professor, Department of Environmental Medicine

Keywords
lung infection and inflammation
Summary

We have investigated the mechanism for the deterioration in immune status produced by tuberculosis in AIDS patients. We have observed that tuberculosis accelerates AIDS by enhancing viral replication and mutation in the lung. Tuberculosis also alters chemokine co-receptor expression on macrophages creating a permissive environment for production of pathogenic viral phenotypes. In the absence of inflammation, alveolar macrophages do not support HIV-1 replication. This suggests that without pneumonia, cellular factors actively inhibit viral replication in the lung. We searched for transcription factors that repress the HIV-1 LTR promoter in the absence of inflammation and found that alveolar macrophages normally express dominant negative transcription factors that represses the HIV-1 LTR. Production of these transcriptional repressors is a novel interferon response. Monocytes are unable to produce the repressors and so investigation of blood monocytes did not reveal this pathway that controls HIV-1 replication in the lung. Differentiation of monocytes to macrophages is required for production of the transcriptional repressors and antiviral effect of interferon or IL-10. During tuberculosis, expression of this repressor is lost. Lymphocyte/macrophage or PMN/macrophage contact is required for loss of the dominate-negative transcription factors. Signaling through both CD40 and CD80/86 is required for de-repression; this in combination proinflammatory cytokines or reactive oxygen intermediates are necessary and sufficient for the high level of HIV-1 replication observed during tuberculosis. De-repression of macrophages mediated through co-stimulatory molecule signaling is a novel mechanism of immune activation leading to enhanced HIV replication in the innate and cellular immune response.

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Professor, Department of Medicine

Professor, Department of Environmental Medicine

Assistant Program Director (Genomics) GCRC

MD from State University of New York at Stony Brook

Cleven, Krystal L; Ye, Kenny; Zeig-Owens, Rachel; Hena, Kerry M; Montagna, Cristina; Shan, Jidong; Hosgood, H Dean; Jaber, Nadia; Weiden, Michael D; Colbeth, Hilary L; Goldfarb, David G; Spivack, Simon D; Prezant, David J

International journal of environmental research & public health. 2019 05 23; 16(10):

Liu, Charles; Putman, Barbara; Singh, Ankura; Zeig-Owens, Rachel; Hall, Charles B; Schwartz, Theresa; Webber, Mayris P; Cohen, Hillel W; Fazzari, Melissa J; Prezant, David J; Weiden, Michael D

International journal of environmental research & public health. 2019 05 13; 16(9):

Wu, Benjamin G; Sulaiman, Imran; Wang, Jing; Shen, Nan; Clemente, Jose C; Li, Yonghua; Laumbach, Robert J; Lu, Shou-En; Udasin, Iris; Le-Hoang, Oanh; Perez, Alan; Alimokhtari, Shahnaz; Black, Kathleen; Plietz, Michael; Twumasi, Akosua; Sanders, Haley; Melacha, Patrick; Kapoor, Bianca; Scaglione, Benjamin D; Wang, Anbang; Blazoski, Cameron; Weiden, Michael D; Rapoport, David M; Harrison, Denise; Chitkara, Nishay; Vicente, Eugenio; Marin, José M; Sunderram, Jag; Ayappa, Indu; Segal, Leopoldo N

American journal of respiratory & critical care medicine. 2019 Jan 01; 199(1):99-109

Singh, Ankura; Liu, Charles; Putman, Barbara; Zeig-Owens, Rachel; Hall, Charles B; Schwartz, Theresa; Webber, Mayris P; Cohen, Hillel W; Berger, Kenneth I; Nolan, Anna; Prezant, David J; Weiden, Michael D

Chest. 2018 Dec; 154(6):1301-1310

Putman, Barbara; Zeig-Owens, Rachel; Singh, Ankura; Hall, Charles B; Schwartz, Theresa; Webber, Mayris P; Cohen, Hillel W; Prezant, David J; Bachert, Claus; Weiden, Michael D

Occupational & environmental medicine. 2018 Dec; 75(12):884-889

Tsay, Jun-Chieh J; Wu, Benjamin G; Badri, Michelle H; Clemente, Jose C; Shen, Nan; Meyn, Peter; Li, Yonghua; Yie, Ting-An; Lhakhang, Tenzin; Olsen, Evan; Murthy, Vivek; Michaud, Gaetane; Sulaiman, Imran; Tsirigos, Aristotelis; Heguy, Adriana; Pass, Harvey; Weiden, Michael D; Rom, William N; Sterman, Daniel H; Bonneau, Richard; Blaser, Martin J; Segal, Leopoldo N

American journal of respiratory & critical care medicine. 2018 Nov 01; 198(9):1188-1198

Webber, Mayris P; Liu, Yang; Cohen, Hillel W; Schwartz, Theresa; Weiden, Michael D; Kelly, Kerry; Ortiz, Viola; Zeig-Owens, Rachel; Jaber, Nadia; Colbeth, Hilary L; Prezant, David J

American journal of industrial medicine. 2018 Jun 20;

Zeig-Owens, Rachel; Singh, Ankura; Aldrich, Thomas K; Hall, Charles B; Schwartz, Theresa; Webber, Mayris P; Cohen, Hillel W; Kelly, Kerry J; Nolan, Anna; Prezant, David J; Weiden, Michael D

Annals of the American Thoracic Society. 2018 02; 15(2):173-183