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OVERVIEW OF HIV VIROLOGY

OVERVIEW OF HIV VIROLOGY

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OVERVIEW OF HIV VIROLOGY

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  1. OVERVIEW OF HIV VIROLOGY BY EKEZIE F.M.C.

  2. INTRODUCTION AND VIROLOGY OF HIV • Hx: • 1978 Unusual diseases among gays in USA • 1980 31 deaths in USA • 1981 PCP and Oropharyngeal candidiasis in 5 young homosexuals • 1982 Dx linked to blood. AIDS first used in July 27 • 1983 Virus isolated (Instirtut Pasteur) • 1987 AZT discovered • 2002 501,669 deaths in USA • Dx • Topical issue today. • Far reaching health, economical, social and political impact world wide.

  3. VIROLOGY • An RNA Virus • A retrovirus of lentivirus family • Cannot replicate outside living host. • Has 2 variants – HIV 1 & 2 • HIV I has subtypes A – H

  4. STRUCTURE • Bar shaped electron dense core • 2 short RNA strand (9200 base pairs) • Enzyme RT, protease, RNAse, Integrase • Envelope lipid bilayer • About 72 surface projections – gp120 The structural components, including the key antigenic components, of human immunodeficiency virus are diagrammed here.

  5. Genome has 3 major genes – gag, pol, env. • env. – gp120, transmb. Gp41 • gag – nucleocapsid proteins, P55, P40, P24 = core Antigen • pol – enzyme proteins. P66. P51 (RT) P11 (protease) P32 (integrase). • High ability to mutate easily due to error rate of RT.(1;2000 nucleotide) • = cells resistant to immune attack, more cytotoxic, can generate syncitia more readily and can resist drug therapy

  6. MODE OF TRANSMISSION A) Implicated in transmission are: • Blood or any fluid containing visible blood. • Semen • Vaginal Secretions • Breast Milk • HIV containing cultures or culture media

  7. Fluids that present a theoretical risk are • Synovial fluid • CSF • Pleural fluid, peritoneal fluid • Pericardial fluid, Amniotic fluid. • No significant risk: Saliva, Urine, Sweat and Tear

  8. B) Process of Infection • Transfusion of blood and blood product • Sexual intercourse (Homo, Hetero) • I.V. drug abuse, ear piercing, manicure and pedicure, barbing , tattoos • Needle prick • Mucosal exposure • Risk of exposure of intact skin have not been quantified.

  9. Skin cuts with surgical blade, hollow needle, broken glass ware, that is visibly contaminated with blood. • Human bite with bleeding by a HIV patient who has visible bleeding into the mouth. • Splash on a mucosal surface by blood, visibly bloody fluid or infective material. • Perinatal transmission = 7 – 71%

  10. MECHANISM OF INFECTION • Primary infects cells with CD4 Cell surface (R) molecules and Chemokine (R). • Helper T lymphocytes, macrophages, blood monocytes, N.K. cells, Dendritic cells, Langerhan’s cells, Haematopoetic stem cells, endothelial cells, microglia, gastrointestinal epith. cells.

  11. Human immunodeficiency virus is shown crossing the mucosa of the genital tract to infect CD4+ T-lymphocytes. A Langerhans cell in the epithelium is shown in red in this diagram.

  12. The interaction of HIV gp120 with the CD4 receptor is shown here. The chemokine coreceptor in the cell membrane induces a conformational change in gp41 that allows fusion of virus with cell membrane.

  13. Binding → fusion or endocytosis → Release of RNA → reverse transcription of RNA to proviral DNA → inserted into host cell genomic DNA → HIV provirus replicated by the host and released by budding. There may be lysis of infected cell with release of virions.

  14. EFFECT ON IMMUNE SYSTEM • Depletion of helper T cells → ↓CMI. • Destruction of dendritic cells of damage to the thymus. • Immune dysregulation associated with production of autoantibodies, immune complexes and persistent complement activation.

  15. Disorder of Ab production, delayed hypersensitivity and macrophage function. • Depletion of IgA containing jejunal and rectal plasma cells. • Vulnerable to opportunistic infection, increase risk of cancer (Kaposi sarcoma, NHL, Squamous cell Ca of cervix & anus) development and malnutrition due to decrease in nutrient absorption and metabolism.

  16. REVISED CDC CLASSIFICATION OF HIV DISEASE • Based on CD4 cell count • Based on clinical features • Category I: - CD4 > 500/µl or > 28%. 2: - CD4 200 – 499/µl or 14-28% 3: - CD4 <200/µl or <14%.

  17. B) Clinical Categories Category A: Asymptomatic, PGL, Acute primary HIV infection. Category B: Oropharyngeal candidiasis, vulvovaginal candidiasis, Cxal dysplasia, loss of up to 10% of body weight, diarrhoea of > 1month, Shingles, Hairy leukoplakia. Category C: Opportunistic infections, PCP, Kaposi’s Sarcoma, toxoplasmosis, MTB, cryptococcosis, extranodal high grade B cell lymphoma

  18. CONCLUSION • HIV is about 23years old, but has caused a great deal of devastation to mankind • It weak outside but strong inside • It cripples the immune system • The surgeon is particularly vulnerable • The rate of mutation in the virus is yet to be checked by modern day pharmacotherapy • There is need to protect the surgeon.