Priming and activation of human neutrophils by HIV accessory proteins
Tsai, Paul Chi-Lin
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Neutrophils are the first primary host defense against infectious agents or non-self substances at the sites of inflammation. NADPH is the major enzyme involved in producing toxic superoxide anions required to generate reactive oxygen species. The NADPH Oxidase is a multicomponent enzyme composed of an integral membrane heterodimeric flavohemoprotein known as cytochrome b subscript 558 consisting of gp91phox and p22phox,located at the plasma membrane, secretory vesicles and specific granules. The cytosolic proteins consist of p47phox, p67phox, p40 phox and small G protein Rac2, exists in the cytosol as a complex. Human immunodeficiency virus (HIV) causes the host to develop AIDS by destroying the CD4+ T cells resulting in severe immune depression which leads to an array of opportunistic infections and tumors. Oral manifestations of HIV including oral candidiasis, oral hairy leukoplakia, human papillomavirus (HPV) related warts, aphthous-like ulcers. Kaposis's sarcoma and periodontitis. It is not fully clear how HIV impacts on other cell types such as neutrophils during the infection. Since neutrophils play a major role as the first line of non-specific defense against invading pathogens, oxidative stress may be an important aspect of the pathogenesis. This process could be regulated by multiple routes in neutrophils either through direct or indirect mechanisms. Since neutrophils do not have the direct recognition capability through CD4 receptor on their surfaces, indirect activation has been speculated to be a part of the neutrophil involvement during HIV infection. Throughout the life cycle of the HIV virus, there are several core(Gag, Pol and Env), regulatory (Tat, Rev) and accessory proteins (Nef, Vif, Vpr and Vpu) that are made from the virus which some are released to enhance the virulence of the virus. Studies have found that these accessory proteins have an array of effects on the neutrophils which potentially could contribute to the immune dysregulation and opportunistic infections often seen in HIV infections and the development of AIDS. In this study, we tested whether Tat, Rev and Nef stimulated neutrophil response. The results show that the HIV accessory proteins Tat, Rev and Nef can act as activating, priming or inhibiting agents employed by the virus to increase its infectivity and to orchestrate the immune mayhem favorable in pathogenesis of HIV infection.
PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact email@example.com.Thesis (MSD) --Boston University, Henry M. Goldman School of Dental Medicine, 2011 (Department of Periodontology and Oral Biology).Includes bibliographic references: leaves 76-85.
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