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Retroviruses. Human immunodeficiency virus. Oncogenic viruses. Mechanisms of viral oncogenesis Classification • Family Retroviridae • Subfamilies: • Lentivirinae • Oncovirinae • Spumavirinae Species: HIV-1, HIV-2 Human T-cell leukemia virus Structure of HIV Major antigens of HIV • 1. 2. • 1. • 1. 2. • Envelope antigens: gp 120 gp 41 Shell antigen: p 18 Core antigens: p 24 (matrix protein) p 7; p 9 Viral enzymes – p11 (integrase); p31 (protease); p 51 (reverse transcriptase) Epidemiology • 1. 2. 3. Three modes of transmission: sexual intercourse parenteral perinatal Pathogenesis • • • • • • • • Virus affects cells, carrying CD4 receptor T- lymphocytes (helper), B- lymphocytes, monocytes, macrophages, glial cells, microglia, follicular dendritic cells Live cycle of the HIV into infected cell Releasing of the progeny virions from infected T-helper by budding Clinical stages • Group 1 – Acute HIV infection. • Group 2 – Asymptomatic infection • Group 3 - Persistent generalized lymphadenopathy • Group 4 – Syptomatic HIV infections (AIDS) HIV-associated opportunistic infections • Bacterial infections: tuberculosis, shigellosis, salmonellosis, mycobacteriosis, staphylococcal and streptococcal purulent infections, etc. • Fungal infections: generalized candidosis, cryptococcal infection, histoplasmosis • Protozoan invasions: pneumocystosis, toxoplasmosis, amoebaean dysentery, lambliosis • Viral infections: generalized herpetic infection, CMV, VEB, sarcoma Kaposhi Sarcoma Kaposhi Laboratory diagnosis Specific tests for early diagnosis of HIV infections: 1. Antigen detections 2. Detection of viral nucleic acid Laboratory diagnosis during seroconversion period: Antibody detection: • Primary: ELISA test (anti gp120, anti gp41) • Confirming: Western blot test Non-specific tests (immune status assay) Tests for opportunistic infections and tumors Main markers of the HIV-infection in different stages of disease Prevention and therapy Prevention – non-specific Antiretroviral drugs include: • Nucleoside inhibitors • Non-nucleoside inhibitors of reverse transcriptase • Viral protease inhibitors • Fusion inhibitor Oncogenic Viruses • Viruses that produce tumours in their natural hosts or in experimental animals or induce malignant transformation of cell in culture, are known as oncogenic viruses. List of oncogenic viruses onc(+) • RNA viruses 1. Retroviruses Avian leucosis viruses Murine leucosis viruses Mammary tumour viruses of mice Leucosis-sarcoma viruses of various animals Human T-cell leukemia viruses List of oncogenic viruses • DNA viruses 1. Papovavirus • Papillomaviruses of human beings, rabbits and other animals • Polyomavirus • Simian virus 40 • BK and JV viruses 2. Poxvirus • Molluscum contagiosum virus • Yaba virus • Shope fibroma Papillomas (warts) List of oncogenic viruses (onc(-) 3. Adenovirus • Many human or nonhuman types 4. Herpes viruses • Epstein-Barr virus • Herpes simplex virus types 1 and 2 • Cytomegalovirus 5. Hepatitis B and C viruses – primary hepatocellular carcinoma Oncogenes • Viral oncogenes (V-onc). • Cellular oncogenes (C-onc) • Protooncogenes Mechanisms of viral oncogenesis of RNAviruses • Following hypothesis are suggested: • Provirus hypothesis • Protovirus hypothesis • DNA oncogenic virus hypothesis