ingest cdrApp 2018-06-13T18:27:59.262Z 51cd2fe2-3fd7-401f-a923-a97bc3db68a2 modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-06-13T19:30:37.178Z Setting exclusive relation addDatastream MD_TECHNICAL fedoraAdmin 2018-06-13T19:30:48.517Z Adding technical metadata derived by FITS addDatastream MD_FULL_TEXT fedoraAdmin 2018-06-13T19:31:00.506Z Adding full text metadata extracted by Apache Tika modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-06-13T19:31:23.419Z Setting exclusive relation modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-11T16:04:53.012Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-18T11:37:06.047Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-21T20:26:27.767Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-27T21:42:06.121Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-12T11:45:45.824Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-17T17:04:11.024Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-03-21T22:05:19.506Z Kurtis Host Author Department of Microbiology and Immunology School of Medicine Interaction of Kaposi’s Sarcoma-associated Herpesvirus with the Host Immune System Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent for three human malignancies; Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). KSHV-related diseases primarily manifest in immunocompromised hosts such as HIV positive patients, iatrogenic immune suppression, and geriatric populations. However, some subtypes of KS exist in the absence of obvious immune deficiency and remain poorly understood. KS is the leading cause of cancer in the sub-Saharan African nation of Malawi. Therefore, we sought to characterize the current clinical burden of KS in Lilongwe, Malawi, the capital city. We found that the majority of KS cases were associated with HIV. Interestingly, 9% of cases were in HIV naïve patients, suggesting a significant burden of the endemic subtype of KS. Our results suggest a needed emphasis for endemic KS research, a poorly understood subtype, as it represents a significant proportion of Malawi’s leading cancer. KSHV is recognized by the immune system, however, it encodes multiple mechanisms for thwarting effective immune responses. One mechanism implicated in escaping immune clearance is programmed death ligand 1 (PD-L1) overexpression. PD-L1 is a co-inhibitory molecule which interacts with the programmed death 1 (PD-1) receptor on T cells. PD-1:PD-L1 engagement blocks T cell receptor (TCR) signaling resulting in reduced T cell activation. Chronic PD-1:PD-L1 ligation results in T cell exhaustion. Tumor cells have been found to utilize PD-L1 to escape immune elimination. Current treatment targeting PD-L1 in certain cancer types is showing clinical efficacy. Therefore, we sought to determine if KSHV could increase PD-L1 expression. We found that KSHV is able to increase PD-L1 expression in human monocytes following infection. In addition, the cytokine profile showed a proinflammatory milieu. Our report is the first to show direct KSHV increase of PD-L1 expression and suggests that PD-L1 targeted therapeutics may have a role in KSHV mediated diseases. Spring 2018 2018 Virology Immunology Kaposi's sarcoma, KSHV, PD-L1 eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Blossom Damania Thesis advisor Lishan Su Thesis advisor Stanley Lemon Thesis advisor Cary Moody Thesis advisor Dirk Dittmer Thesis advisor text Kurtis Host Author Department of Microbiology and Immunology School of Medicine Interaction of Kaposi’s Sarcoma-associated Herpesvirus with the Host Immune System Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent for three human malignancies; Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). KSHV-related diseases primarily manifest in immunocompromised hosts such as HIV positive patients, iatrogenic immune suppression, and geriatric populations. However, some subtypes of KS exist in the absence of obvious immune deficiency and remain poorly understood. KS is the leading cause of cancer in the sub-Saharan African nation of Malawi. Therefore, we sought to characterize the current clinical burden of KS in Lilongwe, Malawi, the capital city. We found that the majority of KS cases were associated with HIV. Interestingly, 9% of cases were in HIV naïve patients, suggesting a significant burden of the endemic subtype of KS. Our results suggest a needed emphasis for endemic KS research, a poorly understood subtype, as it represents a significant proportion of Malawi’s leading cancer. KSHV is recognized by the immune system, however, it encodes multiple mechanisms for thwarting effective immune responses. One mechanism implicated in escaping immune clearance is programmed death ligand 1 (PD-L1) overexpression. PD-L1 is a co-inhibitory molecule which interacts with the programmed death 1 (PD-1) receptor on T cells. PD-1:PD-L1 engagement blocks T cell receptor (TCR) signaling resulting in reduced T cell activation. Chronic PD-1:PD-L1 ligation results in T cell exhaustion. Tumor cells have been found to utilize PD-L1 to escape immune elimination. Current treatment targeting PD-L1 in certain cancer types is showing clinical efficacy. Therefore, we sought to determine if KSHV could increase PD-L1 expression. We found that KSHV is able to increase PD-L1 expression in human monocytes following infection. In addition, the cytokine profile showed a proinflammatory milieu. Our report is the first to show direct KSHV increase of PD-L1 expression and suggests that PD-L1 targeted therapeutics may have a role in KSHV mediated diseases. Spring 2018 2018 Virology Immunology Kaposi's sarcoma, KSHV, PD-L1 eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Blossom Damania Thesis advisor Lishan Su Thesis advisor Stanley Lemon Thesis advisor Cary Moody Thesis advisor Dirk Dittmer Thesis advisor text Kurtis Host Author Department of Microbiology and Immunology School of Medicine Interaction of Kaposi’s Sarcoma-associated Herpesvirus with the Host Immune System Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent for three human malignancies; Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). KSHV-related diseases primarily manifest in immunocompromised hosts such as HIV positive patients, iatrogenic immune suppression, and geriatric populations. However, some subtypes of KS exist in the absence of obvious immune deficiency and remain poorly understood. KS is the leading cause of cancer in the sub-Saharan African nation of Malawi. Therefore, we sought to characterize the current clinical burden of KS in Lilongwe, Malawi, the capital city. We found that the majority of KS cases were associated with HIV. Interestingly, 9% of cases were in HIV naïve patients, suggesting a significant burden of the endemic subtype of KS. Our results suggest a needed emphasis for endemic KS research, a poorly understood subtype, as it represents a significant proportion of Malawi’s leading cancer. KSHV is recognized by the immune system, however, it encodes multiple mechanisms for thwarting effective immune responses. One mechanism implicated in escaping immune clearance is programmed death ligand 1 (PD-L1) overexpression. PD-L1 is a co-inhibitory molecule which interacts with the programmed death 1 (PD-1) receptor on T cells. PD-1:PD-L1 engagement blocks T cell receptor (TCR) signaling resulting in reduced T cell activation. Chronic PD-1:PD-L1 ligation results in T cell exhaustion. Tumor cells have been found to utilize PD-L1 to escape immune elimination. Current treatment targeting PD-L1 in certain cancer types is showing clinical efficacy. Therefore, we sought to determine if KSHV could increase PD-L1 expression. We found that KSHV is able to increase PD-L1 expression in human monocytes following infection. In addition, the cytokine profile showed a proinflammatory milieu. Our report is the first to show direct KSHV increase of PD-L1 expression and suggests that PD-L1 targeted therapeutics may have a role in KSHV mediated diseases. Spring 2018 2018 Virology Immunology Kaposi's sarcoma, KSHV, PD-L1 eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Blossom Damania Thesis advisor Lishan Su Thesis advisor Stanley Lemon Thesis advisor Cary Moody Thesis advisor Dirk Dittmer Thesis advisor text Kurtis Host Author Department of Microbiology and Immunology School of Medicine Interaction of Kaposi’s Sarcoma-associated Herpesvirus with the Host Immune System Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent for three human malignancies; Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). KSHV-related diseases primarily manifest in immunocompromised hosts such as HIV positive patients, iatrogenic immune suppression, and geriatric populations. However, some subtypes of KS exist in the absence of obvious immune deficiency and remain poorly understood. KS is the leading cause of cancer in the sub-Saharan African nation of Malawi. Therefore, we sought to characterize the current clinical burden of KS in Lilongwe, Malawi, the capital city. We found that the majority of KS cases were associated with HIV. Interestingly, 9% of cases were in HIV naïve patients, suggesting a significant burden of the endemic subtype of KS. Our results suggest a needed emphasis for endemic KS research, a poorly understood subtype, as it represents a significant proportion of Malawi’s leading cancer. KSHV is recognized by the immune system, however, it encodes multiple mechanisms for thwarting effective immune responses. One mechanism implicated in escaping immune clearance is programmed death ligand 1 (PD-L1) overexpression. PD-L1 is a co-inhibitory molecule which interacts with the programmed death 1 (PD-1) receptor on T cells. PD-1:PD-L1 engagement blocks T cell receptor (TCR) signaling resulting in reduced T cell activation. Chronic PD-1:PD-L1 ligation results in T cell exhaustion. Tumor cells have been found to utilize PD-L1 to escape immune elimination. Current treatment targeting PD-L1 in certain cancer types is showing clinical efficacy. Therefore, we sought to determine if KSHV could increase PD-L1 expression. We found that KSHV is able to increase PD-L1 expression in human monocytes following infection. In addition, the cytokine profile showed a proinflammatory milieu. Our report is the first to show direct KSHV increase of PD-L1 expression and suggests that PD-L1 targeted therapeutics may have a role in KSHV mediated diseases. Spring 2018 2018 Virology Immunology Kaposi's sarcoma, KSHV, PD-L1 eng Doctor of Philosophy Dissertation Microbiology and Immunology Blossom Damania Thesis advisor Lishan Su Thesis advisor Stanley Lemon Thesis advisor Cary Moody Thesis advisor Dirk Dittmer Thesis advisor text University of North Carolina at Chapel Hill Degree granting institution Kurtis Host Creator Department of Microbiology and Immunology School of Medicine Interaction of Kaposi’s Sarcoma-associated Herpesvirus with the Host Immune System Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent for three human malignancies; Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). KSHV-related diseases primarily manifest in immunocompromised hosts such as HIV positive patients, iatrogenic immune suppression, and geriatric populations. However, some subtypes of KS exist in the absence of obvious immune deficiency and remain poorly understood. KS is the leading cause of cancer in the sub-Saharan African nation of Malawi. Therefore, we sought to characterize the current clinical burden of KS in Lilongwe, Malawi, the capital city. We found that the majority of KS cases were associated with HIV. Interestingly, 9% of cases were in HIV naïve patients, suggesting a significant burden of the endemic subtype of KS. Our results suggest a needed emphasis for endemic KS research, a poorly understood subtype, as it represents a significant proportion of Malawi’s leading cancer. KSHV is recognized by the immune system, however, it encodes multiple mechanisms for thwarting effective immune responses. One mechanism implicated in escaping immune clearance is programmed death ligand 1 (PD-L1) overexpression. PD-L1 is a co-inhibitory molecule which interacts with the programmed death 1 (PD-1) receptor on T cells. PD-1:PD-L1 engagement blocks T cell receptor (TCR) signaling resulting in reduced T cell activation. Chronic PD-1:PD-L1 ligation results in T cell exhaustion. Tumor cells have been found to utilize PD-L1 to escape immune elimination. Current treatment targeting PD-L1 in certain cancer types is showing clinical efficacy. Therefore, we sought to determine if KSHV could increase PD-L1 expression. We found that KSHV is able to increase PD-L1 expression in human monocytes following infection. In addition, the cytokine profile showed a proinflammatory milieu. Our report is the first to show direct KSHV increase of PD-L1 expression and suggests that PD-L1 targeted therapeutics may have a role in KSHV mediated diseases. Virology Immunology Kaposi's sarcoma; KSHV; PD-L1 eng Doctor of Philosophy Dissertation Microbiology and Immunology Blossom Damania Thesis advisor Lishan Su Thesis advisor Stanley Lemon Thesis advisor Cary Moody Thesis advisor Dirk Dittmer Thesis advisor text University of North Carolina at Chapel Hill Degree granting institution 2018 2018-05 Kurtis Host Author Department of Microbiology and Immunology School of Medicine Interaction of Kaposi’s Sarcoma-associated Herpesvirus with the Host Immune System Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent for three human malignancies; Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). KSHV-related diseases primarily manifest in immunocompromised hosts such as HIV positive patients, iatrogenic immune suppression, and geriatric populations. However, some subtypes of KS exist in the absence of obvious immune deficiency and remain poorly understood. KS is the leading cause of cancer in the sub-Saharan African nation of Malawi. Therefore, we sought to characterize the current clinical burden of KS in Lilongwe, Malawi, the capital city. We found that the majority of KS cases were associated with HIV. Interestingly, 9% of cases were in HIV naïve patients, suggesting a significant burden of the endemic subtype of KS. Our results suggest a needed emphasis for endemic KS research, a poorly understood subtype, as it represents a significant proportion of Malawi’s leading cancer. KSHV is recognized by the immune system, however, it encodes multiple mechanisms for thwarting effective immune responses. One mechanism implicated in escaping immune clearance is programmed death ligand 1 (PD-L1) overexpression. PD-L1 is a co-inhibitory molecule which interacts with the programmed death 1 (PD-1) receptor on T cells. PD-1:PD-L1 engagement blocks T cell receptor (TCR) signaling resulting in reduced T cell activation. Chronic PD-1:PD-L1 ligation results in T cell exhaustion. Tumor cells have been found to utilize PD-L1 to escape immune elimination. Current treatment targeting PD-L1 in certain cancer types is showing clinical efficacy. Therefore, we sought to determine if KSHV could increase PD-L1 expression. We found that KSHV is able to increase PD-L1 expression in human monocytes following infection. In addition, the cytokine profile showed a proinflammatory milieu. Our report is the first to show direct KSHV increase of PD-L1 expression and suggests that PD-L1 targeted therapeutics may have a role in KSHV mediated diseases. Spring 2018 2018 Virology Immunology Kaposi's sarcoma, KSHV, PD-L1 eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Blossom Damania Thesis advisor Lishan Su Thesis advisor Stanley Lemon Thesis advisor Cary Moody Thesis advisor Dirk Dittmer Thesis advisor text Kurtis Host Author Department of Microbiology and Immunology School of Medicine Interaction of Kaposi’s Sarcoma-associated Herpesvirus with the Host Immune System Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent for three human malignancies; Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). KSHV-related diseases primarily manifest in immunocompromised hosts such as HIV positive patients, iatrogenic immune suppression, and geriatric populations. However, some subtypes of KS exist in the absence of obvious immune deficiency and remain poorly understood. KS is the leading cause of cancer in the sub-Saharan African nation of Malawi. Therefore, we sought to characterize the current clinical burden of KS in Lilongwe, Malawi, the capital city. We found that the majority of KS cases were associated with HIV. Interestingly, 9% of cases were in HIV naïve patients, suggesting a significant burden of the endemic subtype of KS. Our results suggest a needed emphasis for endemic KS research, a poorly understood subtype, as it represents a significant proportion of Malawi’s leading cancer. KSHV is recognized by the immune system, however, it encodes multiple mechanisms for thwarting effective immune responses. One mechanism implicated in escaping immune clearance is programmed death ligand 1 (PD-L1) overexpression. PD-L1 is a co-inhibitory molecule which interacts with the programmed death 1 (PD-1) receptor on T cells. PD-1:PD-L1 engagement blocks T cell receptor (TCR) signaling resulting in reduced T cell activation. Chronic PD-1:PD-L1 ligation results in T cell exhaustion. Tumor cells have been found to utilize PD-L1 to escape immune elimination. Current treatment targeting PD-L1 in certain cancer types is showing clinical efficacy. Therefore, we sought to determine if KSHV could increase PD-L1 expression. We found that KSHV is able to increase PD-L1 expression in human monocytes following infection. In addition, the cytokine profile showed a proinflammatory milieu. Our report is the first to show direct KSHV increase of PD-L1 expression and suggests that PD-L1 targeted therapeutics may have a role in KSHV mediated diseases. Spring 2018 2018 Virology Immunology Kaposi's sarcoma, KSHV, PD-L1 eng Doctor of Philosophy Dissertation Microbiology and Immunology Blossom Damania Thesis advisor Lishan Su Thesis advisor Stanley Lemon Thesis advisor Cary Moody Thesis advisor Dirk Dittmer Thesis advisor text University of North Carolina at Chapel Hill Degree granting institution Kurtis Host Creator Department of Microbiology and Immunology School of Medicine Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent for three human malignancies; Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). KSHV-related diseases primarily manifest in immunocompromised hosts such as HIV positive patients, iatrogenic immune suppression, and geriatric populations. However, some subtypes of KS exist in the absence of obvious immune deficiency and remain poorly understood. KS is the leading cause of cancer in the sub-Saharan African nation of Malawi. Therefore, we sought to characterize the current clinical burden of KS in Lilongwe, Malawi, the capital city. We found that the majority of KS cases were associated with HIV. Interestingly, 9% of cases were in HIV naïve patients, suggesting a significant burden of the endemic subtype of KS. Our results suggest a needed emphasis for endemic KS research, a poorly understood subtype, as it represents a significant proportion of Malawi’s leading cancer. KSHV is recognized by the immune system, however, it encodes multiple mechanisms for thwarting effective immune responses. One mechanism implicated in escaping immune clearance is programmed death ligand 1 (PD-L1) overexpression. PD-L1 is a co-inhibitory molecule which interacts with the programmed death 1 (PD-1) receptor on T cells. PD-1:PD-L1 engagement blocks T cell receptor (TCR) signaling resulting in reduced T cell activation. Chronic PD-1:PD-L1 ligation results in T cell exhaustion. Tumor cells have been found to utilize PD-L1 to escape immune elimination. Current treatment targeting PD-L1 in certain cancer types is showing clinical efficacy. Therefore, we sought to determine if KSHV could increase PD-L1 expression. We found that KSHV is able to increase PD-L1 expression in human monocytes following infection. In addition, the cytokine profile showed a proinflammatory milieu. Our report is the first to show direct KSHV increase of PD-L1 expression and suggests that PD-L1 targeted therapeutics may have a role in KSHV mediated diseases. 2018-05 2018 Virology Immunology Kaposi's sarcoma; KSHV; PD-L1 eng Doctor of Philosophy Dissertation Blossom Damania Thesis advisor Lishan Su Thesis advisor Stanley Lemon Thesis advisor Cary Moody Thesis advisor Dirk Dittmer Thesis advisor text University of North Carolina at Chapel Hill Degree granting institution Host_unc_0153D_17705.pdf uuid:4bf5dd49-4114-4e95-b556-42c01bddf3f1 2020-06-13T00:00:00 2018-04-15T17:02:20Z proquest application/pdf 2303185