Introduction to HIV/AIDS

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1 HIV/AIDS Seminar 5

2 Welcome Back

3 Introduction to HIV/AIDS

4 History of HIV/AIDS It is now thought that HIV came from a similar virus found in chimpanzees - SIV. HIV probably entered North America around 1970 In 1981, the CDC noticed clusters of Kaposi s sarcoma in gay men in NY and San Francisco, which led to the disease to be called GRID (Gay Related Immune Deficiency). Kaposi s Sarcoma

5 History of HIV/AIDS By 1982 the disease was apparent in heterosexuals and was renamed AIDS Scientists identify HIV (initially called HTLV-III or LAV) as the cause of AIDS AZT is the first drug approved for treating AIDS 1.1 million deaths in 2015 Primarily in Africa

6 History of HIV/AIDS By 1982 the disease was apparent in heterosexuals and was renamed AIDS (Acquired Immune Deficiency Syndrome) Scientists identify HIV (initially called HTLV-III or LAV) as the cause of AIDS AZT is the first drug approved for treating AIDS 1.1 million deaths in 2015 Primarily in Africa

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9 AIDS Acquired Immune Deficiency Syndrome Approximately 81,000 Canadians are living with AIDS today (2.3/1000)

10 Prevalence of New Infections

11 # of People in Canada living with HIV

12 Cases of HIV infection and AIDS in the United States and Dependent Areas, 2006 Sex of adults and adolescents with HIV/AIDS diagnosed during 2006 Transmission categories of adults and adolescents with HIV/AIDS diagnosed during

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14 What is AIDS A = Acquired, not inherited. I = Weakens the Immune system. D = Creates a Deficiency of CD4+ cells in the immune system. S = Syndrome, or a group of illnesses taking place at the same time. Two types of HIV : HIV-1 and HIV-2 HIV-2 is lower transmissibility. HIV-2 develops more slowly. MTCT (Mother to child transmission) is relatively rare with HIV-2. HIV-2 is found primarily in West Africa. HIV-1 is more common worldwide, prevalent in North America

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17 Two Components of Adaptive Immune System Humoral ( molecule mediated immunity) B-Cells Plasma Cells Antibodies Cellular (cellular mediated immunity) CD8+ T-Cells Direct Cellular Killing CD4+ T-Cells Recruitment of other immune cells (inflammatory response) Adaptive Immunity

18 X X X X CD4 Cells

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20 HIV - AIDS HIV develops in to AIDS when the CD4 + T cell count drops below 200 cells per µl of serum or secondary diseases associated with HIV infection present C/P (Clinical Pictures):- Stages clinical spectrum :- 1- asymptomatic sero-negative. 2- pre AIDS generalized lymphadenopathy. 3- AIDS related complex. 4- AIDS with opportunistic infection as: Kaposi Sarcoma candidiasis pneumonia, tuberculosis, cervical cancer,

21 CHRONIC VIRAL INFECTIONS

22 VIRAL INFECTIONS Abortive Infections: occur in non-permissive cell, no virus produced Persistent Infections: Generally do not cause cell death. Often production is negligible, slow, sporadic, or very localized Chronic: limited production Latent: persist in latent phase (no or minimal production) Slow: prolonged incubation, significant physiological/morphological changes in host cell Transforming: viral DNA enters human genome (may be indefinite) May be oncogenic Host cells may experience morphological, physiological, biochemical, and genotoxic damage. This damage may be characteristic to a viral family.

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26 Acknowledgment: E. Cassol

27 AIDS Research Fighting Back

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30 Edana Cassol Assistant Professor Health Science Carleton University

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32 IL-7 receptor recovery on CD8 T-cells isolated from HIV+ patients is inhibited by the HIV Tat protein. Faller EM, McVey MJ, MacPherson PA. PLoS One Jul 17;9(7):e102677

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36 The virus is easier to control when active but difficult to root out when dormant New therapies aim to use a kick and kill strategy to temporarily activate the virus and then eradicate when it becomes active The issue is how to knock-down the virus so that it is not pathogentic when activated A new compound L-HIPPO targets HIV protein Pr55 and prevents the virus from moving to the membrane

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38 NOTABLE CASES The Mississippi Baby Aggressive anti-retroviral therapy cleared the child of any detectable viral particles. The mother stopped treatment for 5 months but the child was again found to be infected a year later The Boston Patients:

39 STEM CELL THERAPY The CCR5 receptor on the surface of CD4 T-cells is extremely important in allowing HIV to enter the cell Patients have been treated with new CD4 cells that have a mutated version of this receptor

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41 THE BERLIN PATIENT Three factors could cured Timothy s HIV either independently or in combination 1. The doctors destroyed Brown s own immune system with chemotherapy and whole body irradiation to prepare him for his bone marrow transplant. His 2. Oncologist, Gero Hütter, brilliantly thought that if he found a donor with a CCR5 mutation he might not only cure the leukemia but also help rid Brown s body of HIV. 3. The third possibility the immune system attacked remnants of his old one that held HIV-infected cells, a process known as graft versus host disease.

42 The Berlin Patient

43 A QUICK LOOK AT CYSTIC FIBROSIS

44 WHAT IS CF Cystic Fibrosis is the most common life-threating recessive genetic disorder in causcasians 1 in 29 white people carry atleast one copy of the defective CF gene The CF gene was identified in 1989 and mapped to chromosome 7 There are over 1300 different mutations in CF The cystic fibrosis gene codes for the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) which controls calcium movement across membranes CFTR is expressed in epithelial cells mostly in the lungs and GI tract Dysfunction leads to water imbalances and thick mucous secretions

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47 CF LEADS TO BIOFILMS IN THE LUNGS Collection of surface-associated microbes Enclosed by extracellular, mostly polysaccharide matrix Can include noncellular material Mineral crystals Corrosive particles Blood Other substances Dartmouth Undergraduate Journal of Science First colony adheres to surface and anchors permanently if not removed immediately Biofilms form a strong, protective structure that protects and sustains the colony against a variety of threats 47 Copyright 2016 by Elsevier Inc. All rights reserved.

48 Cells function differently depending on: the current biofilm architecture and/or their location within the film psedo-tissue structure BIOFILMS 48 Copyright 2016 by Elsevier Inc. All rights reserved.

49 likeitfunny.com ANTIBIOTICS Mechanisms, Classes, and the Development of Resistance

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