This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Genital herpes caused by both HSV types 1 and 2 remains a common and chronic infection for which there is no effective vaccine. Despite effective HSV antivirals, two disconcerting trends have been observed: 1) the prevalence of genital herpes continues to rise with approximately 1.6 million new cases occurring annually;2) there has been an increased incidence of recurrent genital lesions. These trends are especially alarming considering the role HSV-2 may play in facilitating other STIs. Significantly, HSV-2 genital infection is an important cofactor for HIV acquisition, with statistical modeling attributing almost half of all HIV transmission to HSV-2 infections. HSV-2 infections contribute to increased STIs by either modulating cell-intrinsic innate recognition and response pathways or increasing the inflammatory milieu within the genital tract mucosa. The molecular mechanisms through which HSV-2 impairs the immune response are still poorly understood. Our preliminary studies have recently identified a potential """"""""adaptor"""""""" domain within HSV glycoprotein K (gK) that is able to modulate a cadre of signal transduction pathways involved in innate recognition and response to invading pathogens. We therefore hypothesize that HSV-2 gK protein subverts the innate immune response from a protective response to a chronic inflammatory process that aides the survival of HSV-2 and promotes infections by other infectious agents. We proposed to dissect the mechanisms by which HSV gK suppresses inflammation-associated pathogen recognition and response pathways and thereby promotes the establishment of a persistent lifelong infection. Understanding these mechanisms will provide important information towards the development of new anti-HSV therapies or to the development of an effective vaccine.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR021970-07
Application #
8360451
Study Section
Special Emphasis Panel (ZRR1-CR-B (01))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
7
Fiscal Year
2011
Total Cost
$425,231
Indirect Cost
Name
Louisiana State Univ Hsc New Orleans
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Rodriguez, Paulo C; Ochoa, Augusto C; Al-Khami, Amir A (2017) Arginine Metabolism in Myeloid Cells Shapes Innate and Adaptive Immunity. Front Immunol 8:93
Sanchez, Maria Dulfary; Ochoa, Augusto C; Foster, Timothy P (2016) Development and evaluation of a host-targeted antiviral that abrogates herpes simplex virus replication through modulation of arginine-associated metabolic pathways. Antiviral Res 132:13-25
Dai, Lu; Bai, Lihua; Lin, Zhen et al. (2016) Transcriptomic analysis of KSHV-infected primary oral fibroblasts: The role of interferon-induced genes in the latency of oncogenic virus. Oncotarget 7:47052-47060
Schieffelin, John; Moses, Lina M; Shaffer, Jeffrey et al. (2016) Clinical validation trial of a diagnostic for Ebola Zaire antigen detection: Design rationale and challenges to implementation. Clin Trials 13:66-72
Fletcher, Matthew; Ramirez, Maria E; Sierra, Rosa A et al. (2015) l-Arginine depletion blunts antitumor T-cell responses by inducing myeloid-derived suppressor cells. Cancer Res 75:275-83
Dai, Lu; Trillo-Tinoco, Jimena; Bai, Aiping et al. (2015) Ceramides promote apoptosis for virus-infected lymphoma cells through induction of ceramide synthases and viral lytic gene expression. Oncotarget 6:24246-60
Geng, Degui; Kaczanowska, Sabina; Tsai, Alexander et al. (2015) TLR5 Ligand-Secreting T Cells Reshape the Tumor Microenvironment and Enhance Antitumor Activity. Cancer Res 75:1959-1971
Dai, Lu; Chen, Yihan; Bonstaff, Karlie et al. (2015) Induction of hyaluronan production by oncogenic KSHV and the contribution to viral pathogenesis in AIDS patients. Cancer Lett 362:158-66
Dai, Lu; Trillo-Tinoco, Jimena; Cao, Yueyu et al. (2015) Targeting HGF/c-MET induces cell cycle arrest, DNA damage, and apoptosis for primary effusion lymphoma. Blood 126:2821-31
Dai, Lu; Cao, Yueyu; Chen, Yihan et al. (2015) Genomic analysis of xCT-mediated regulatory network: Identification of novel targets against AIDS-associated lymphoma. Oncotarget 6:12710-22

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